PLGA-based nanoparticles as cancer drug delivery systems.

Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained- release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.

[1]  Tae Gwan Park,et al.  Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[2]  V. Labhasetwar,et al.  Biodegradable nanoparticles for cytosolic delivery of therapeutics. , 2007, Advanced drug delivery reviews.

[3]  Steven P Schwendeman,et al.  Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. , 2008, International journal of pharmaceutics.

[4]  G. Stoner,et al.  Formulation and In Vitro-In Vivo Evaluation of Black Raspberry Extract-Loaded PLGA/PLA Injectable Millicylindrical Implants for Sustained Delivery of Chemopreventive Anthocyanins , 2010, Pharmaceutical Research.

[5]  G. Adams,et al.  High affinity restricts the localization and tumor penetration of single-chain fv antibody molecules. , 2001, Cancer research.

[6]  Robert Gurny,et al.  Poly(lactic acid) nanoparticles labeled with biologically active Neutravidin for active targeting. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[7]  R. Bodmeier,et al.  Stability of poly(D,L-lactide-co-glycolide) and leuprolide acetate in in-situ forming drug delivery systems. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[8]  Vladimir P Torchilin,et al.  Reversal of multidrug resistance by co-delivery of tariquidar (XR9576) and paclitaxel using long-circulating liposomes. , 2011, International journal of pharmaceutics.

[9]  F. Boey,et al.  In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[10]  F. Veiga,et al.  Nanoencapsulation II. Biomedical applications and current status of peptide and protein nanoparticulate delivery systems. , 2006, Nanomedicine : nanotechnology, biology, and medicine.

[11]  Wei Liu,et al.  Tumor necrosis factor alpha blocking peptide loaded PEG-PLGA nanoparticles: preparation and in vitro evaluation. , 2007, International journal of pharmaceutics.

[12]  C. Tros de Ilarduya,et al.  Pharmacodynamics of cisplatin-loaded PLGA nanoparticles administered to tumor-bearing mice. , 2010, European journal of pharmaceutics and biopharmaceutics.

[13]  T. Allen Ligand-targeted therapeutics in anticancer therapy , 2002, Nature Reviews Cancer.

[14]  U. Nielsen,et al.  Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. , 2006, Cancer research.

[15]  Catarina Pinto Reis,et al.  Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. , 2006, Nanomedicine : nanotechnology, biology, and medicine.

[16]  Jayanth Panyam,et al.  Fluorescence and electron microscopy probes for cellular and tissue uptake of poly(D,L-lactide-co-glycolide) nanoparticles. , 2003, International journal of pharmaceutics.

[17]  G. Sharma,et al.  Biodegradable in situ gelling system for subcutaneous administration of ellagic acid and ellagic acid loaded nanoparticles: evaluation of their antioxidant potential against cyclosporine induced nephrotoxicity in rats. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[18]  P. Couvreur,et al.  Nanocarriers’ entry into the cell: relevance to drug delivery , 2009, Cellular and Molecular Life Sciences.

[19]  Lisbeth Illum,et al.  Long circulating microparticulate drug carriers , 1995 .

[20]  Y. Horikiri,et al.  Rupture and drug release characteristics of multi-reservoir type microspheres with poly(dl-lactide-co-glycolide) and poly(dl-lactide). , 2006, International journal of pharmaceutics.

[21]  V. Mohanraj,et al.  Nanoparticles - A Review , 2007 .

[22]  Lisa Brannon-Peppas,et al.  Active targeting schemes for nanoparticle systems in cancer therapeutics. , 2008, Advanced drug delivery reviews.

[23]  F. Selmin,et al.  Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist , 2004, AAPS PharmSci.

[24]  Peter H Lin,et al.  Current advances in research and clinical applications of PLGA-based nanotechnology , 2009, Expert review of molecular diagnostics.

[25]  Wei Liang,et al.  Improving penetration in tumors with nanoassemblies of phospholipids and doxorubicin. , 2007, Journal of the National Cancer Institute.

[26]  Kyung-Hwa Yoo,et al.  Multifunctional nanoparticles for combined doxorubicin and photothermal treatments. , 2009, ACS nano.

[27]  P. Deluca,et al.  A model-dependent approach to correlate accelerated with real-time release from biodegradable microspheres , 2005, AAPS PharmSciTech.

[28]  Patrick Couvreur,et al.  Controlled drug delivery with nanoparticles : current possibilities and future trends , 1995 .

[29]  Wei Zhang,et al.  Synaptic transmission of neural stem cells seeded in 3-dimensional PLGA scaffolds. , 2009, Biomaterials.

[30]  M. Xie,et al.  Bypassing multidrug resistance in human breast cancer cells with lipid/polymer particle assemblies , 2012, International journal of nanomedicine.

[31]  Tae Gwan Park,et al.  Degradation of poly(d,l-lactic acid) microspheres: effect of molecular weight , 1994 .

[32]  M. Alonso,et al.  Formulation of L-asparaginase-loaded poly(lactide-co-glycolide) nanoparticles: influence of polymer properties on enzyme loading, activity and in vitro release. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[33]  Soodabeh Davaran,et al.  Liposome: classification, preparation, and applications , 2013, Nanoscale Research Letters.

[34]  Robert J. Levy,et al.  Nanoparticle drug delivery system for restenosis , 1997 .

[35]  G. Mills,et al.  Determinants of Rapamycin Sensitivity in Breast Cancer Cells , 2004, Clinical Cancer Research.

[36]  H. Lenz,et al.  EGFR Signaling and Drug Discovery , 2010, Oncology.

[37]  N. Zelcer,et al.  On the putative co‐transport of drugs by multidrug resistance proteins , 2006, FEBS letters.

[38]  Steven P Schwendeman,et al.  Pore closing and opening in biodegradable polymers and their effect on the controlled release of proteins. , 2007, Molecular pharmaceutics.

[39]  Shen‐guo Wang,et al.  Preparation of poly(lactide-co-glycolide-co-caprolactone) nanoparticles and their degradation behaviour in aqueous solution , 2006 .

[40]  T. N. Palmer,et al.  The mechanism of liposome accumulation in infarction. , 1984, Biochimica et biophysica acta.

[41]  Si-Shen Feng,et al.  The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. , 2006, Biomaterials.

[42]  A. R. Kulkarni,et al.  Biodegradable polymeric nanoparticles as drug delivery devices. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[43]  R. Gurny,et al.  Aqueous nanodispersions prepared by a salting-out process , 1992 .

[44]  Diane J Burgess,et al.  Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[45]  M. R. Kumar,et al.  Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[46]  Nicholas A Peppas,et al.  Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. , 2006, International journal of pharmaceutics.

[47]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[48]  R. Müller,et al.  'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. , 2000, Colloids and surfaces. B, Biointerfaces.

[49]  H. Chung,et al.  Biodegradable polymeric microspheres with "open/closed" pores for sustained release of human growth hormone. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[50]  Peter Carmeliet,et al.  VEGF as a Key Mediator of Angiogenesis in Cancer , 2005, Oncology.

[51]  B. Gálvez,et al.  MT1-MMP: Universal or particular player in angiogenesis? , 2006, Cancer and Metastasis Reviews.

[52]  M. Ueda,et al.  Influence of the preparation methods on the drug release behaviour of loperamide-loaded nanoparticles. , 1998, Journal of microencapsulation.

[53]  Robert Langer,et al.  Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery. , 2007, Biomaterials.

[54]  B. Aggarwal,et al.  Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. , 2010, Biochemical pharmacology.

[55]  Christine Jérôme,et al.  Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[56]  Ho Seok Lee,et al.  The effect of type of organic phase solvents on the particle size of poly(d,l-lactide-co-glycolide) nanoparticles , 2006 .

[57]  Hatem Fessi,et al.  Nanocapsule formation by interfacial polymer deposition following solvent displacement , 1989 .

[58]  K. Garber Rapamycin may prevent post-transplant lymphoma. , 2001, Journal of the National Cancer Institute.

[59]  B. Aggarwal,et al.  Curcumin: Getting Back to the Roots , 2005, Annals of the New York Academy of Sciences.

[60]  A. Prokop,et al.  Nanovehicular intracellular delivery systems. , 2008, Journal of pharmaceutical sciences.

[61]  J L Cleland,et al.  Sustained release of recombinant human insulin-like growth factor-I for treatment of diabetes. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[62]  S M Moghimi,et al.  Poloxamers and poloxamines in nanoparticle engineering and experimental medicine. , 2000, Trends in biotechnology.

[63]  David A. Cheresh,et al.  Integrins in cancer: biological implications and therapeutic opportunities , 2010, Nature Reviews Cancer.

[64]  Sung Ju Cho,et al.  Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells , 2007, Journal of nanobiotechnology.

[65]  Puneet Utreja,et al.  Novel drug delivery systems for sustained and targeted delivery of anti- cancer drugs: current status and future prospects. , 2010, Current drug delivery.

[66]  U. Pal,et al.  Effects of crystallization and dopant concentration on the emission behavior of TiO2:Eu nanophosphors , 2012, Nanoscale Research Letters.

[67]  C. G. Pitt,et al.  Poly (glycolic acid-co-dl-lactic acid): diffusion or degradation controlled drug delivery? , 1992 .

[68]  T. Kissel,et al.  Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake? , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[69]  K. Derakhshandeh,et al.  Encapsulation of 9-nitrocamptothecin, a novel anticancer drug, in biodegradable nanoparticles: factorial design, characterization and release kinetics. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[70]  Véronique Préat,et al.  To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[71]  J. Kreuter,et al.  Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide) nanoparticles: influence of the formulation parameters. , 2010, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[72]  Y Li,et al.  PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[73]  Robert Gurny,et al.  Drug-loaded nanoparticles : preparation methods and drug targeting issues , 1993 .

[74]  A. Domb,et al.  PLA stereocomplexes for controlled release of somatostatin analogue. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[75]  Soriano,et al.  The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA nanoparticles following oral administration. , 2000, Colloids and surfaces. B, Biointerfaces.

[76]  Mansoor Amiji,et al.  Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs. 1. In vitro evaluations. , 2005, Molecular pharmaceutics.

[77]  J. M. Marchetti,et al.  Zinc(II) phthalocyanine loaded PLGA nanoparticles for photodynamic therapy use. , 2006, International journal of pharmaceutics.

[78]  R K Jain,et al.  Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[79]  W. Friess,et al.  Release mechanisms from gentamicin loaded poly(lactic-co-glycolic acid) (PLGA) microparticles. , 2002, Journal of pharmaceutical sciences.

[80]  F. Zanella,et al.  Toxicological studies of doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma. , 2002, Toxicology letters.

[81]  Murali M. Yallapu,et al.  Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. , 2010, Journal of colloid and interface science.

[82]  M. Rad-Malekshahi,et al.  Preparation and antibacterial activity evaluation of rifampicin-loaded poly lactide-co-glycolide nanoparticles. , 2007, Nanomedicine : nanotechnology, biology, and medicine.

[83]  J. Fariña,et al.  Potential applications of PLGA film-implants in modulating in vitro drugs release. , 2002, International journal of pharmaceutics.

[84]  Tejraj M Aminabhavi,et al.  Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[85]  R. Murthy,et al.  Etoposide-incorporated tripalmitin nanoparticles with different surface charge: Formulation, characterization, radiolabeling, and biodistribution studies , 2004, The AAPS Journal.

[86]  R. Löbenberg,et al.  Influence of the surfactant concentration on the body distribution of nanoparticles. , 1999, Journal of drug targeting.

[87]  M. Pinto,et al.  Natural and synthetic xanthonolignoids: chemistry and biological activities. , 2003, Current medicinal chemistry.

[88]  Chi-Hwa Wang,et al.  In Vitro Sustained Release of Human Immunoglobulin G from Biodegradable Microspheres , 2001 .

[89]  Sudesh Kumar Yadav,et al.  Biodegradable polymeric nanoparticles based drug delivery systems. , 2010, Colloids and surfaces. B, Biointerfaces.

[90]  M. Hidalgo,et al.  The rapamycin-sensitive signal transduction pathway as a target for cancer therapy , 2000, Oncogene.

[91]  Wenjie Song,et al.  Cytotoxicity of Paclitaxel Incorporated in PLGA Nanoparticles on Hypoxic Human Tumor Cells , 2009, Pharmaceutical Research.

[92]  Si-Shen Feng,et al.  Nanoparticles of biodegradable polymers for new-concept chemotherapy , 2004, Expert review of medical devices.

[93]  A. Akbarzadeh,et al.  Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line , 2012, Journal of Nanobiotechnology.

[94]  A. Akbarzadeh,et al.  Synthesis, characterization, and in vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled delivery of doxorubicin. , 2012, Nanotechnology, science and applications.

[95]  J. D. Henderson,et al.  Tissue biocompatibility of kevlar aramid fibers and polymethylmethacrylate, composites in rabbits. , 1987, Journal of biomedical materials research.

[96]  F. Davis The origin of pegnology. , 2002, Advanced Drug Delivery Reviews.

[97]  B. Teicher Molecular targets and cancer therapeutics: discovery, development and clinical validation. , 2000, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[98]  Anders Axelsson,et al.  The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review. , 2011, International journal of pharmaceutics.

[99]  V. Labhasetwar,et al.  Quantification of the force of nanoparticle-cell membrane interactions and its influence on intracellular trafficking of nanoparticles. , 2008, Biomaterials.

[100]  A. Lowman,et al.  Biodegradable nanoparticles for drug delivery and targeting , 2002 .

[101]  J. Cleland,et al.  The Stabilization and Encapsulation of Human Growth Hormone into Biodegradable Microspheres , 1997, Pharmaceutical Research.

[102]  R K Jain,et al.  Understanding barriers to drug delivery: high resolution in vivo imaging is key. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[103]  A. Karydas,et al.  PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[104]  J. Shapiro,et al.  Delivery of rapamycin by PLGA nanoparticles enhances its suppressive activity on dendritic cells. , 2008, Journal of biomedical materials research. Part A.

[105]  Si-Shen Feng,et al.  Nanoparticles of biodegradable polymers for clinical administration of paclitaxel. , 2004, Current medicinal chemistry.

[106]  V. Torchilin,et al.  Drug targeting. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[107]  Kohei Tahara,et al.  Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells. , 2009, International journal of pharmaceutics.

[108]  Chava Kimchi-Sarfaty,et al.  P-glycoprotein: from genomics to mechanism , 2003, Oncogene.

[109]  D. Parkin,et al.  Global cancer statistics in the year 2000. , 2001, The Lancet. Oncology.

[110]  A. Vila,et al.  Design of biodegradable particles for protein delivery. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[111]  R. Alyautdin,et al.  Influence of the type of surfactant on the analgesic effects induced by the peptide dalargin after its delivery across the blood–brain barrier using surfactant-coated nanoparticles , 1997 .

[112]  Patrick Winter,et al.  Applications of Nanotechnology to Atherosclerosis, Thrombosis, and Vascular Biology , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[113]  Lin Mei,et al.  Nanoparticles of Poly(Lactide-Co-Glycolide)-d-a-Tocopheryl Polyethylene Glycol 1000 Succinate Random Copolymer for Cancer Treatment , 2010, Nanoscale research letters.

[114]  J. Siepmann,et al.  PLGA-based drug delivery systems: importance of the type of drug and device geometry. , 2008, International journal of pharmaceutics.

[115]  M. Alonso,et al.  Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[116]  T. Park,et al.  In vitro and in vivo anti-tumor activities of nanoparticles based on doxorubicin-PLGA conjugates. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[117]  C. Astete,et al.  Synthesis and characterization of PLGA nanoparticles , 2006, Journal of biomaterials science. Polymer edition.

[118]  Chengmeng Jin,et al.  Developing a Highly Stable PLGA-mPEG Nanoparticle Loaded with Cisplatin for Chemotherapy of Ovarian Cancer , 2011, PloS one.

[119]  G. Sharma,et al.  Design of Biodegradable Nanoparticles for Oral Delivery of Doxorubicin: In vivo Pharmacokinetics and Toxicity Studies in Rats , 2009, Pharmaceutical Research.

[120]  Mansoor M Amiji,et al.  Multi-functional polymeric nanoparticles for tumour-targeted drug delivery , 2006, Expert opinion on drug delivery.

[121]  Chiara Brignole,et al.  Targeting liposomal chemotherapy via both tumor cell-specific and tumor vasculature-specific ligands potentiates therapeutic efficacy. , 2006, Cancer research.

[122]  S. Sahoo,et al.  Nanotech approaches to drug delivery and imaging. , 2003, Drug discovery today.

[123]  Eric Doelker,et al.  Strategic approaches for overcoming peptide and protein instability within biodegradable nano- and microparticles. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[124]  T Lammers,et al.  Tumour-targeted nanomedicines: principles and practice , 2008, British Journal of Cancer.

[125]  P. Low,et al.  Folate-targeted therapeutic and imaging agents for cancer. , 2009, Current opinion in chemical biology.

[126]  Lai Yeng Lee,et al.  Paclitaxel delivery from PLGA foams for controlled release in post-surgical chemotherapy against glioblastoma multiforme. , 2009, Biomaterials.

[127]  P. Couvreur,et al.  Nanoparticulate systems for the delivery of antisense oligonucleotides. , 2001, Advanced drug delivery reviews.

[128]  R Pasqualini,et al.  Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. , 2000, Cancer research.

[129]  G. Feldmann,et al.  Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy , 2007, Journal of nanobiotechnology.

[130]  J. Vishwanatha,et al.  Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. , 2009, Anticancer research.

[131]  A. Kabanov,et al.  Prevention of MDR development in leukemia cells by micelle-forming polymeric surfactant. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[132]  R. Langer,et al.  Polymers for the sustained release of proteins and other macromolecules , 1976, Nature.

[133]  Robert Gurny,et al.  Preparation and characterization of sterile and freeze-dried sub-200 nm nanoparticles. , 2002, International journal of pharmaceutics.

[134]  S. Simões,et al.  Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[135]  S. Sahoo,et al.  Intracellular trafficking of nuclear localization signal conjugated nanoparticles for cancer therapy. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[136]  R. Gurny,et al.  Biodegradable nanoparticles for direct or two-step tumor immunotargeting. , 2006, Bioconjugate chemistry.

[137]  E. K. Park,et al.  Preparation and characterization of methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) amphiphilic block copolymeric nanospheres for tumor-specific folate-mediated targeting of anticancer drugs. , 2004, Biomaterials.

[138]  Jayanth Panyam,et al.  Rapid endo‐lysosomal escape of poly(DL‐lactide‐coglycolide) nanoparticles: implications for drug and gene delivery , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[139]  Indu Bala,et al.  PLGA nanoparticles in drug delivery: the state of the art. , 2004, Critical reviews in therapeutic drug carrier systems.

[140]  Xiangrong Song,et al.  PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: systematic study of particle size and drug entrapment efficiency. , 2008, International journal of pharmaceutics.

[141]  D. A. Kharkevich,et al.  Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study. , 1998, Journal of microencapsulation.

[142]  Y. Kawashima,et al.  Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease. , 2001, The Journal of pharmacology and experimental therapeutics.

[143]  You Han Bae,et al.  Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[144]  Xiangrong Song,et al.  Reversion of multidrug resistance by co-encapsulation of vincristine and verapamil in PLGA nanoparticles. , 2009, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[145]  Shuming Nie,et al.  Emerging use of nanoparticles in diagnosis and treatment of breast cancer. , 2006, The Lancet. Oncology.

[146]  H. Takano,et al.  The direct activation of human multidrug resistance gene (MDR1) by anticancer agents. , 1989, Biochemical and biophysical research communications.

[147]  J. González,et al.  Transport properties of two finite armchair graphene nanoribbons , 2013, Nanoscale Research Letters.

[148]  A. Coombes,et al.  The preparation of sub-200 nm poly(lactide-co-glycolide) microspheres for site-specific drug delivery , 1993 .

[149]  H. Maeda,et al.  Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[150]  H. Fessi,et al.  Preparation of pseudolatex by nanoprecipitation: Influence of the solvent nature on intrinsic viscosity and interaction constant , 1997 .

[151]  Wolfgang Eiermann,et al.  Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[152]  H. Maeda,et al.  Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[153]  I. Pastan,et al.  Expression of a multidrug-resistance gene in human tumors and tissues. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[154]  M. Foti,et al.  Dexamethasone-containing PLGA superparamagnetic microparticles as carriers for the local treatment of arthritis. , 2009, Biomaterials.

[155]  T. Park,et al.  Degradation of poly(lactic-co-glycolic acid) microspheres: effect of copolymer composition. , 1995, Biomaterials.

[156]  R. Langer,et al.  Poly(Ethylene Oxide)-Modified Poly(β-Amino Ester) Nanoparticles as a pH-Sensitive System for Tumor-Targeted Delivery of Hydrophobic Drugs: Part 2. In Vivo Distribution and Tumor Localization Studies , 2005, Pharmaceutical Research.

[157]  J. Benoit,et al.  Baclofen-loaded microspheres: preparation and efficacy testing in a new rabbit model. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[158]  Fahima Dilnawaz,et al.  Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy. , 2009, Biomaterials.

[159]  Qiang Zhang,et al.  Synchronic release of two hormonal contraceptives for about one month from the PLGA microspheres: in vitro and in vivo studies. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[160]  R. Duncan The dawning era of polymer therapeutics , 2003, Nature Reviews Drug Discovery.

[161]  R. Gurny,et al.  Hypericin-loaded nanoparticles for the photodynamic treatment of ovarian cancer. , 2006, International journal of pharmaceutics.

[162]  J Folkman,et al.  Transplacental carcinogenesis by stilbestrol. , 1971, The New England journal of medicine.

[163]  F Atyabi,et al.  Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents , 2011, International journal of nanomedicine.

[164]  A. Pardakhty,et al.  Role of nanocarrier systems in cancer nanotherapy , 2009, Journal of liposome research.

[165]  C Vigneron,et al.  Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[166]  Si-Shen Feng,et al.  Poly(d,l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs. , 2005, Biomaterials.

[167]  E. Topp,et al.  Chemical degradation of peptides and proteins in PLGA: a review of reactions and mechanisms. , 2008, Journal of pharmaceutical sciences.

[168]  A. Mochizuki,et al.  Controlled release of argatroban from PLA film—Effect of hydroxylesters as additives on enhancement of drug release , 2008 .

[169]  F. Atyabi,et al.  Preparation of PLGA nanoparticles using TPGS in the spontaneous emulsification solvent diffusion method , 2007 .

[170]  Elias Fattal,et al.  Encapsulation of dexamethasone into biodegradable polymeric nanoparticles. , 2007, International journal of pharmaceutics.

[171]  S. Nie,et al.  Therapeutic Nanoparticles for Drug Delivery in Cancer Types of Nanoparticles Used as Drug Delivery Systems , 2022 .

[172]  Ick Chan Kwon,et al.  New Generation of Multifunctional Nanoparticles for Cancer Imaging and Therapy , 2009 .

[173]  S. Feng,et al.  A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[174]  Mouldy Sioud,et al.  Selective targeting of cancer cells using synthetic peptides. , 2003, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[175]  D. A. Kharkevich,et al.  Analgesic activity of the hexapeptide dalargin adsorbed on the surface of polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles , 1995 .

[176]  P. Couvreur,et al.  PEGylated polycyanoacrylate nanoparticles as vector for drug delivery in prion diseases , 2001, Journal of Neuroscience Methods.

[177]  S. Nie,et al.  Nanotechnology applications in cancer. , 2007, Annual review of biomedical engineering.

[178]  P. Couvreur,et al.  Nanoparticles in cancer therapy and diagnosis. , 2002, Advanced drug delivery reviews.

[179]  Tao Xu,et al.  Modification of nanostructured materials for biomedical applications , 2007 .

[180]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[181]  U. Bakowsky,et al.  Preparation and characterization of cationic PLGA nanospheres as DNA carriers. , 2004, Biomaterials.

[182]  S. Sahoo,et al.  PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. , 2011, Advanced drug delivery reviews.

[183]  S. Ostad,et al.  Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA-PEG-folate conjugate. , 2008, Journal of drug targeting.

[184]  Barnett Rosenberg,et al.  Charles F. Kettring prize. Fundamental studies with cisplatin , 1985 .

[185]  Robert Gurny,et al.  Nanoparticles for drug delivery: the need for precision in reporting particle size parameters. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[186]  I. Tannock,et al.  Acid pH in tumors and its potential for therapeutic exploitation. , 1989, Cancer research.

[187]  Lisa Brannon-Peppas,et al.  Doxorubicin-loaded PLGA nanoparticles by nanoprecipitation: preparation, characterization and in vitro evaluation. , 2007, Nanomedicine.

[188]  M. R. Aberturas,et al.  Stability and freeze-drying of cyclosporine loaded poly(D,L lactide-glycolide) carriers. , 1999, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[189]  Michihiro Nakamura,et al.  Nanomedicine for drug delivery and imaging: A promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles , 2007, International journal of cancer.

[190]  R K Jain,et al.  Delivery of novel therapeutic agents in tumors: physiological barriers and strategies. , 1990, Journal of the National Cancer Institute.

[191]  Anil Mahapatro,et al.  Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines , 2011, Journal of nanobiotechnology.

[192]  Jayanth Panyam,et al.  Biodegradable nanoparticles for drug and gene delivery to cells and tissue. , 2003, Advanced drug delivery reviews.

[193]  Effect of different antilipidemic agents and diets on mortality: a systematic review. , 2005 .

[194]  Christine Vauthier,et al.  Methods for the Preparation and Manufacture of Polymeric Nanoparticles , 2009, Pharmaceutical Research.

[195]  H. Ringsdorf Structure and properties of pharmacologically active polymers , 1975 .

[196]  Sung‐Wook Choi,et al.  Design of surface-modified poly(D,L-lactide-co-glycolide) nanoparticles for targeted drug delivery to bone. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[197]  M. Hatziapostolou,et al.  Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[198]  Suming Li,et al.  Biodegradation of PLA/GA polymers: increasing complexity. , 1994, Biomaterials.

[199]  V. Bhardwaj,et al.  Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[200]  Rassoul Dinarvand,et al.  PLGA nanoparticles of different surface properties: preparation and evaluation of their body distribution. , 2008, International journal of pharmaceutics.

[201]  S. Caruthers,et al.  Molecular imaging and therapy of atherosclerosis with targeted nanoparticles , 2007, Journal of magnetic resonance imaging : JMRI.

[202]  Yaodong Jiang,et al.  Paclitaxel-Loaded Poly(n-butylcyanoacrylate) Nanoparticle Delivery System to Overcome Multidrug Resistance in Ovarian Cancer , 2011, Pharmaceutical Research.

[203]  M. Roberts,et al.  In vivo investigation of tolerance and antitumor activity of cisplatin-loaded PLGA-mPEG nanoparticles. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[204]  L. Lim,et al.  Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[205]  G. Bendas,et al.  VCAM-1 directed immunoliposomes selectively target tumor vasculature in vivo. , 2008, Biochimica et biophysica acta.

[206]  C. Ecoffey,et al.  Epidural, intrathecal and plasma pharmacokinetic study of epidural ropivacaine in PLGA-microspheres in sheep model. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[207]  O. Bourdon,et al.  Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules. , 2001, Biomaterials.

[208]  P. Giusti,et al.  Combined drug release from biodegradable bilayer coating for endovascular stents. , 2010, Journal of biomedical materials research. Part B, Applied biomaterials.

[209]  T. Minko Drug targeting to the colon with lectins and neoglycoconjugates. , 2004, Advanced drug delivery reviews.

[210]  Gustavo Helguera,et al.  The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells. , 2006, Clinical immunology.

[211]  M Dunne,et al.  Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles. , 2000, Biomaterials.

[212]  Gert Storm,et al.  Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system , 1995 .

[213]  S. Schwendeman,et al.  Stabilization of Proteins Encapsulated in Cylindrical Poly(lactide-co-glycolide) Implants: Mechanism of Stabilization by Basic Additives , 2000, Pharmaceutical Research.

[214]  S. Davis,et al.  PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[215]  S. Wise Nanocarriers as an emerging platform for cancer therapy , 2007 .

[216]  M. Gottesman,et al.  Targeting multidrug resistance in cancer , 2006, Nature Reviews Drug Discovery.

[217]  S. Chan,et al.  Prodrugs for dermal delivery , 1989 .

[218]  J. Panyam,et al.  Injectable sustained release microparticles of curcumin: a new concept for cancer chemoprevention. , 2010, Cancer research.

[219]  M. Alonso,et al.  Approaches to improve the association of amikacin sulphate to poly(alkylcyanoacrylate) nanoparticles , 1991 .

[220]  A. Akbarzadeh,et al.  Magnetic nanoparticles: preparation, physical properties, and applications in biomedicine , 2012, Nanoscale Research Letters.

[221]  T. Tsuruo,et al.  Role of aminopeptidase N (CD13) in tumor‐cell invasion and extracellular matrix degradation , 1993, International journal of cancer.

[222]  V. Torchilin,et al.  Which polymers can make nanoparticulate drug carriers long-circulating? , 1995 .

[223]  Dar-Bin Shieh,et al.  Stabilizer-free poly(lactide-co-glycolide) nanoparticles for multimodal biomedical probes. , 2008, Biomaterials.

[224]  B. Ratner,et al.  Biomaterial surfaces. , 1987, Journal of biomedical materials research.

[225]  S. Parveen,et al.  Polymeric nanoparticles for cancer therapy , 2008, Journal of drug targeting.

[226]  Y. Schneider,et al.  PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[227]  R. A. Jain,et al.  The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. , 2000, Biomaterials.

[228]  S. Jonnalagadda,et al.  A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery , 2000, AAPS PharmSciTech.

[229]  A. C. Hunter,et al.  Nanomedicine: current status and future prospects , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[230]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[231]  Sven Frokjaer,et al.  Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. , 2005, International journal of pharmaceutics.

[232]  P. Couvreur,et al.  Design of triptorelin loaded nanospheres for transdermal iontophoretic administration. , 2001, International journal of pharmaceutics.

[233]  T. Kissel,et al.  Characterization of a homologous series of D,L-lactic acid oligomers; a mechanistic study on the degradation kinetics in vitro. , 2003, Biomaterials.

[234]  V. Préat,et al.  PLGA-based nanoparticles: an overview of biomedical applications. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[235]  B. Gander,et al.  In vitro phagocytosis and monocyte-macrophage activation with poly(lactide) and poly(lactide-co-glycolide) microspheres. , 2002, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[236]  Lin Zheng,et al.  The use of submicron/nanoscale PLGA implants to deliver paclitaxel with enhanced pharmacokinetics and therapeutic efficacy in intracranial glioblastoma in mice. , 2010, Biomaterials.

[237]  S. Yalkowsky,et al.  Solubilization of rapamycin. , 2001, International journal of pharmaceutics.

[238]  H. Sato,et al.  Preparation and characterization of poly(lactic-co-glycolic acid) microspheres for targeted delivery of a novel anticancer agent, taxol. , 1996, Chemical & pharmaceutical bulletin.

[239]  A. Akbarzadeh,et al.  Preparation and in vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers , 2012, International journal of nanomedicine.

[240]  T. Tice,et al.  Preparation of injectable controlled-release microcapsules by a solvent-evaporation process , 1985 .

[241]  D. Quintanar-Guerrero,et al.  Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. , 1998, Drug development and industrial pharmacy.

[242]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.