Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

[1]  M. McGuckin,et al.  Colloidal mesoporous silica nanoparticles enhance the biological activity of resveratrol. , 2016, Colloids and surfaces. B, Biointerfaces.

[2]  B. Cavalcanti,et al.  Preclinical genotoxicology of nor-β-lapachone in human cultured lymphocytes and Chinese hamster lung fibroblasts. , 2011, Chemical research in toxicology.

[3]  Michael F Clarke,et al.  The biology of cancer stem cells. , 2007, Annual review of cell and developmental biology.

[4]  Samuel C. Hooker.  On the Oxidation of 2-Hydroxy-1,4-naphthoquinone Derivatives with Alkaline Potassium Permanganate1,2 , 1936 .

[5]  A. Ayala,et al.  The encapsulation of β-lapachone in 2-hydroxypropyl-β-cyclodextrin inclusion complex into liposomes: a physicochemical evaluation and molecular modeling approach. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[6]  M. Shen,et al.  Diagnostics: The prostate-cancer metabolome , 2009, Nature.

[7]  L. Pardo,et al.  Synthesis and pharmacophore modeling of naphthoquinone derivatives with cytotoxic activity in human promyelocytic leukemia HL-60 cell line. , 2007, Journal of medicinal chemistry.

[8]  Sachin S Thakur,et al.  Enhancing delivery and cytotoxicity of resveratrol through a dual nanoencapsulation approach. , 2016, Journal of colloid and interface science.

[9]  Divya K. Nair,et al.  Naphthoquinone-based chalcone hybrids and derivatives: synthesis and potent activity against cancer cell lines , 2015 .

[10]  V. Ferreira,et al.  Cytotoxic, Trypanocidal Activities and Physicochemical Parameters of nor-β-Lapachone-based 1,2,3-Triazoles , 2009 .

[11]  G. Barratt,et al.  Nanotechnologies and controlled release systems for the delivery of antisense oligonucleotides and small interfering RNA , 2009, British journal of pharmacology.

[12]  R. Perez-Fernandez,et al.  Administration of the optimized β-Lapachone-poloxamer-cyclodextrin ternary system induces apoptosis, DNA damage and reduces tumor growth in a human breast adenocarcinoma xenograft mouse model. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  E. L. Albuquerque,et al.  Adsorption of ascorbic acid on the C60 fullerene. , 2008, The journal of physical chemistry. B.

[14]  I. McNeish,et al.  The intracellular uptake of CD95 modified paclitaxel-loaded poly(lactic-co-glycolic acid) microparticles. , 2011, Biomaterials.

[15]  Sudhir S Chakravarthi,et al.  Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles. , 2011, International journal of pharmaceutics.

[16]  F. Emery,et al.  Synthesis of quinoidal molecules: strategies towards bioactive compounds with an emphasis on lapachones. , 2013, European journal of medicinal chemistry.

[17]  Matthew D. McDermott,et al.  The hydrogel template method for fabrication of homogeneous nano/microparticles. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[18]  C. K. Andrade,et al.  3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives: synthesis and cytotoxicity against cancer cell lines. , 2010, Journal of medicinal chemistry.

[19]  Z. Yue,et al.  Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and angiogenesis in an orthotopic glioma model. , 2010, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[20]  I. Egli,et al.  Dephytinisation with Intrinsic Wheat Phytase and Iron Fortification Significantly Increase Iron Absorption from Fonio (Digitaria exilis) Meals in West African Women , 2013, PloS one.

[21]  A. Godec,et al.  Modus operandi of controlled release from mesoporous matrices: a theoretical perspective. , 2011, Physical chemistry chemical physics : PCCP.

[22]  A. Pardee,et al.  Induction of Apoptosis by β-Lapachone in Human Prostate Cancer Cells , 1995 .

[23]  W. Chui,et al.  Nanoparticulate Delivery System Targeted to Tumor Neovasculature for Combined Anticancer and Antiangiogenesis Therapy , 2011, Pharmaceutical Research.

[24]  M. Nowak,et al.  Distant Metastasis Occurs Late during the Genetic Evolution of Pancreatic Cancer , 2010, Nature.

[25]  L. Costa-Lotufo,et al.  Growth inhibitory effects of 3'-nitro-3-phenylamino nor-beta-lapachone against HL-60: a redox-dependent mechanism. , 2012, Toxicology in vitro : an international journal published in association with BIBRA.

[26]  A. Vis,et al.  Key targets of hormonal treatment of prostate cancer. Part 1: the androgen receptor and steroidogenic pathways , 2009, BJU international.

[27]  E. L. Albuquerque,et al.  Two-Level Adsorption of Ibuprofen on C60 Fullerene for Transdermal Delivery: Classical Molecular Dynamics and Density Functional Theory Computations , 2011 .

[28]  Insoo Kim,et al.  Doxorubicin-loaded highly porous large PLGA microparticles as a sustained- release inhalation system for the treatment of metastatic lung cancer. , 2012, Biomaterials.

[29]  B. Weinberg,et al.  Beta-lapachone-containing PEG-PLA polymer micelles as novel nanotherapeutics against NQO1-overexpressing tumor cells. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[30]  A. Khan,et al.  Anticancer efficacy of perillyl alcohol-bearing PLGA microparticles , 2012, International journal of nanomedicine.

[31]  F. Kalembo,et al.  UGT2B17 Polymorphism and Risk of Prostate Cancer: A Meta-Analysis , 2013, ISRN oncology.

[32]  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.

[33]  V. Bajic,et al.  Anti-cancer activities of diospyrin, its derivatives and analogues. , 2010, European journal of medicinal chemistry.

[34]  R. Deberardinis,et al.  The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. , 2008, Cell metabolism.

[35]  M. E. Gil-Alegre,et al.  Local Delivery of Cannabinoid-Loaded Microparticles Inhibits Tumor Growth in a Murine Xenograft Model of Glioblastoma Multiforme , 2013, PloS one.

[36]  D. Moura,et al.  Potent antileukemic action of naphthoquinoidal compounds: evidence for an intrinsic death mechanism based on oxidative stress and inhibition of DNA repair , 2013 .

[37]  J. D. S. Filho,et al.  Design, synthesis and application of fluorescent 2,1,3-benzothiadiazole-triazole-linked biologically active lapachone derivatives , 2014 .

[38]  W. Ni,et al.  Genetic Polymorphisms of GSTM1, GSTT1, and GSTP1 with Prostate Cancer Risk: A Meta-Analysis of 57 Studies , 2012, PloS one.

[39]  L. Fieser,et al.  Naphthoquinone antimalarials; the Hooker oxidation reaction. , 1948, Journal of the American Chemical Society.

[40]  Jane E. Visvader,et al.  Cells of origin in cancer , 2011, Nature.

[41]  F. Brimo,et al.  PTEN genomic deletion predicts prostate cancer recurrence and is associated with low AR expression and transcriptional activity , 2012, BMC Cancer.

[42]  Sanjeev Banerjee,et al.  Nano-constructed Carriers Loaded With Antioxidant: Boon For Cardiovascular System. , 2015, Current pharmaceutical design.

[43]  A. Neves,et al.  Nanoscale Delivery of Resveratrol towards Enhancement of Supplements and Nutraceuticals , 2016, Nutrients.

[44]  M. O. Moraes,et al.  Synthesis and potent antitumor activity of new arylamino derivatives of nor-β-lapachone and nor-α-lapachone , 2007 .

[45]  A. Pardee,et al.  Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol: combining drugs imposes different artificial checkpoints. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[46]  S. Yoon,et al.  Systemic delivery and preclinical evaluation of Au nanoparticle containing beta-lapachone for radiosensitization. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[47]  J. Montero,et al.  β-Lapachone analogs with enhanced antiproliferative activity. , 2012, European journal of medicinal chemistry.

[48]  J. Bolton,et al.  Role of quinones in toxicology. , 2000, Chemical research in toxicology.

[49]  N. Lopes,et al.  Fragmentation studies and electrospray ionization mass spectrometry of lapachol: protonated, deprotonated and cationized species. , 2010, Rapid communications in mass spectrometry : RCM.

[50]  Chi‐Hwa Wang,et al.  In vitro study of anticancer drug doxorubicin in PLGA-based microparticles. , 2005, Biomaterials.

[51]  D. Ross,et al.  NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones. , 2012, Biochemical pharmacology.

[52]  L. Costa-Lotufo,et al.  Oxidative stress induction by (+)-cordiaquinone J triggers both mitochondria-dependent apoptosis and necrosis in leukemia cells. , 2010, Chemico-biological interactions.

[53]  Eduardo J. Salustiano,et al.  Comparison of the cytotoxic effect of lapachol, α-lapachone and pentacyclic 1,4-naphthoquinones on human leukemic cells , 2010, Investigational New Drugs.

[54]  V Emuss,et al.  The Molecular Biology of Cancer , 2006, British Journal of Cancer.

[55]  D. L. da Mota,et al.  Toxicological assessment of beta‐lapachone on organs from pregnant and non‐pregnant rats , 2009, Phytotherapy research : PTR.

[56]  M. Rubin,et al.  Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. , 2013, European urology.