Polymer-Based Nanoparticle Strategies for Insulin Delivery

Diabetes mellitus (DM) is a chronic metabolic illness estimated to have affected 451 million individuals to date, with this number expected to significantly rise in the coming years. There are two main classes of this disease, namely type 1 diabetes (T1D) and type 2 diabetes (T2D). Insulin therapy is pivotal in the management of diabetes, with diabetic individuals taking multiple daily insulin injections. However, the mode of administration has numerous drawbacks, resulting in poor patient compliance. In order to optimize insulin therapy, novel drug delivery systems (DDSes) have been suggested, and alternative routes of administration have been investigated. A novel aspect in the field of drug delivery was brought about by the coalescence of polymeric science and nanotechnology. In addition to polymeric nanoparticles (PNPs), insulin DDSes can incorporate the use of nanoplatforms/carriers. A combination of these systems can bring about novel formulations and lead to significant improvements in the drug delivery system (DDS) with regard to therapeutic efficacy, bioavailability, increased half-life, improved transport through physical and chemical barriers, and controlled drug delivery. This review will discuss how recent developments in polymer chemistry and nanotechnology have been employed in a multitude of platforms as well as in administration routes for the safe and efficient delivery of insulin for the treatment of DM.

[1]  Li Wang,et al.  Advances in phenylboronic acid-based closed-loop smart drug delivery system for diabetic therapy. , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[2]  P. A. Shah,et al.  Natural biodegradable polymers based nano‐formulations for drug delivery: A review , 2019, International journal of pharmaceutics.

[3]  Fatemeh Mohabatpour,et al.  A Review on Bioengineering Approaches to Insulin Delivery: A Pharmaceutical and Engineering Perspective. , 2019, Macromolecular bioscience.

[4]  K. Greish,et al.  Nanotechnology in insulin delivery for management of diabetes. , 2019, Pharmaceutical nanotechnology.

[5]  Hongbo Zhang,et al.  Engineering synthetic artificial pancreas using chitosan hydrogels integrated with glucose-responsive microspheres for insulin delivery. , 2019, Materials science & engineering. C, Materials for biological applications.

[6]  W. Zhang,et al.  Concanavalin A-sugar affinity based system: Binding interactions, principle of glucose-responsiveness, and modulated insulin release for diabetes care. , 2019, International journal of biological macromolecules.

[7]  G. Fetih,et al.  Development of bi-polymer lipid hybrid nanocarrier (BLN) to improve the entrapment and stability of insulin for efficient oral delivery , 2019, Journal of Drug Delivery Science and Technology.

[8]  Shaohua Jiang,et al.  Stimuli-responsive bio-based polymeric systems and their applications. , 2019, Journal of materials chemistry. B.

[9]  Xin Zhang,et al.  Enhanced oral insulin delivery via surface hydrophilic modification of chitosan copolymer based self‐assembly polyelectrolyte nanocomplex , 2019, International journal of pharmaceutics.

[10]  Yangchao Luo,et al.  Recent advances of polysaccharide-based nanoparticles for oral insulin delivery. , 2018, International journal of biological macromolecules.

[11]  Yatin R. Gokarn,et al.  Non-invasive delivery strategies for biologics , 2018, Nature Reviews Drug Discovery.

[12]  S. Mishra,et al.  PREPARATION AND CHARACTERIZATION OF CHITOSAN NANOPARTICLES OF INSULIN FOR NASAL DELIVERY , 2018, Journal of Drug Delivery and Therapeutics.

[13]  Y. S. Zhang,et al.  Supercritical Fluid-Assisted Decoration of Nanoparticles on Porous Microcontainers for Codelivery of Therapeutics and Inhalation Therapy of Diabetes. , 2018, ACS biomaterials science & engineering.

[14]  F. Atyabi,et al.  Synthesis and characterization of a novel peptide-grafted Cs and evaluation of its nanoparticles for the oral delivery of insulin, in vitro, and in vivo study , 2018, International journal of nanomedicine.

[15]  M. Vallet‐Regí,et al.  Mesoporous silica nanoparticles in nanomedicine applications , 2018, Journal of Materials Science: Materials in Medicine.

[16]  S. Sigrist,et al.  Oral insulin delivery, the challenge to increase insulin bioavailability: Influence of surface charge in nanoparticle system , 2018, International journal of pharmaceutics.

[17]  M. J. Santander-Ortega,et al.  PEG‐PGA enveloped octaarginine‐peptide nanocomplexes: An oral peptide delivery strategy , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[18]  J. Shaw,et al.  IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. , 2018, Diabetes research and clinical practice.

[19]  Xiaomei Wang,et al.  Development of poly(hydroxyethyl methacrylate) nanogel for effective oral insulin delivery , 2018, Pharmaceutical development and technology.

[20]  B. Sarmento,et al.  Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides , 2018, Peptides.

[21]  Crispin R Dass,et al.  Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin. , 2018, International journal of pharmaceutics.

[22]  Manisha Pandey,et al.  Nanotechnology based approaches for anti-diabetic drugs delivery. , 2018, Diabetes research and clinical practice.

[23]  Ranran Chang,et al.  Glucose-responsive biopolymer nanoparticles prepared by co-assembly of concanavalin A and amylopectin for insulin delivery , 2018 .

[24]  M. Teodorescu,et al.  Biomaterials of Poly(vinyl alcohol) and Natural Polymers , 2018 .

[25]  Liefeng Zhang,et al.  A cell-penetrating peptide mediated chitosan nanocarriers for improving intestinal insulin delivery. , 2017, Carbohydrate polymers.

[26]  Jianhai Yang,et al.  Glucose‐responsive insulin release: Analysis of mechanisms, formulations, and evaluation criteria , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[27]  J. Xie,et al.  Advances in pH-Sensitive Polymers for Smart Insulin Delivery. , 2017, Macromolecular rapid communications.

[28]  Michael S Strano,et al.  Glucose-responsive insulin by molecular and physical design , 2017, Nature Chemistry.

[29]  Wim E Hennink,et al.  Nanogels for intracellular delivery of biotherapeutics , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[30]  Baojian Wu,et al.  Selenium nanoparticles as versatile carriers for oral delivery of insulin: Insight into the synergic antidiabetic effect and mechanism. , 2017, Nanomedicine : nanotechnology, biology, and medicine.

[31]  Lei Wu,et al.  [Preparation of nanoparticles for sustained insulin release using poly (ethylene glycol) -poly (ε-caprolactone)-poly (N, N-diethylamino-2-ethylmethaerylate)]. , 2017, Nan fang yi ke da xue xue bao = Journal of Southern Medical University.

[32]  P. P. Kundu,et al.  Preparation of polyurethane–alginate/chitosan core shell nanoparticles for the purpose of oral insulin delivery , 2017 .

[33]  Shanshan Xiao,et al.  Glucose Oxidase-Based Glucose-Sensitive Drug Delivery for Diabetes Treatment , 2017, Polymers.

[34]  Max K. Leong,et al.  Encapsulation of 16-Hydroxycleroda-3,13-Dine-16,15-Olide in Mesoporous Silica Nanoparticles as a Natural Dipeptidyl Peptidase-4 Inhibitor Potentiated Hypoglycemia in Diabetic Mice , 2017, Nanomaterials.

[35]  E. Bonifacio,et al.  Type 1 diabetes mellitus , 2017, Nature Reviews Disease Primers.

[36]  Pierre P. D. Kondiah,et al.  Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System , 2017, AAPS PharmSciTech.

[37]  M. Prausnitz,et al.  Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes , 2017, The AAPS Journal.

[38]  Guohua Jiang,et al.  Oral delivery of insulin using CaCO3-based composite nanocarriers with hyaluronic acid coatings , 2017 .

[39]  R. Martínez‐Máñez,et al.  Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. , 2017, Chemistry.

[40]  Xiaoguang Fan,et al.  Temperature and glucose dual-responsive carriers bearing poly(N-isopropylacrylamide) and phenylboronic acid for insulin-controlled release: A review , 2017 .

[41]  I. Rupenthal,et al.  Hyaluronic Acid Coated Albumin Nanoparticles for Targeted Peptide Delivery to the Retina. , 2017, Molecular pharmaceutics.

[42]  M. Alonso,et al.  Rational design of protamine nanocapsules as antigen delivery carriers , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[43]  Fan Huang,et al.  Development of shell cross-linked nanoparticles based on boronic acid-related reactions for self-regulated insulin delivery , 2017, Journal of biomaterials science. Polymer edition.

[44]  V. Préat,et al.  Emerging delivery platforms for mucosal administration of biopharmaceuticals: a critical update on nasal, pulmonary and oral routes , 2017, Expert opinion on drug delivery.

[45]  Kruti S Soni,et al.  Nanogels: An overview of properties, biomedical applications and obstacles to clinical translation. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[46]  K. Shea,et al.  Synthesis of surfactant-free hydroxypropyl methylcellulose nanogels for controlled release of insulin. , 2016, Carbohydrate polymers.

[47]  Zhen Gu,et al.  Stimuli‐responsive delivery of therapeutics for diabetes treatment , 2016, Bioengineering & translational medicine.

[48]  H. Santos,et al.  Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[49]  Jiaxi Wang,et al.  Cell-penetrating peptides as noninvasive transmembrane vectors for the development of novel multifunctional drug-delivery systems. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[50]  Mohammad Ramezani,et al.  Dextran-b-poly(lactide-co-glycolide) polymersome for oral delivery of insulin: In vitro and in vivo evaluation. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[51]  X. Wen,et al.  Bioengineering Strategies for the Treatment of Type I Diabetes. , 2016, Journal of biomedical nanotechnology.

[52]  T. Garg,et al.  Development of transferosomal gel for trans-dermal delivery of insulin using iodine complex , 2016, Drug delivery.

[53]  H. M. Nielsen,et al.  Cell-Penetrating Peptides as Carriers for Oral Delivery of Biopharmaceuticals. , 2016, Basic & clinical pharmacology & toxicology.

[54]  Shweta Sharma,et al.  Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: A mucoadhesive and pH responsive carrier for improved oral delivery of insulin. , 2016, Acta biomaterialia.

[55]  X. Xiong,et al.  Study on uptake of PLA-Pluronic P85-PLA nanoparticles with Caco-2 cells , 2015 .

[56]  A. Nayak,et al.  Chitosan‐based Interpenetrating Polymeric Network Systems for Sustained Drug Release , 2015 .

[57]  Zhen Gu,et al.  Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery , 2015, Proceedings of the National Academy of Sciences.

[58]  M. Ansari,et al.  Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats , 2015, Drug delivery.

[59]  Chunsheng Xiao,et al.  Competitive binding-accelerated insulin release from a polypeptide nanogel for potential therapy of diabetes , 2015 .

[60]  Prabha Garg,et al.  Molecular mechanism of poly(vinyl alcohol) mediated prevention of aggregation and stabilization of insulin in nanoparticles. , 2015, Molecular pharmaceutics.

[61]  S. Armes,et al.  Synthesis and characterization of poly(amino acid methacrylate)-stabilized diblock copolymer nano-objects , 2015 .

[62]  S. Ostad,et al.  Development of Acid-Resistant Alginate/Trimethyl Chitosan Nanoparticles Containing Cationic β-Cyclodextrin Polymers for Insulin Oral Delivery , 2015, AAPS PharmSciTech.

[63]  Zhen Gu,et al.  Emerging micro- and nanotechnology based synthetic approaches for insulin delivery. , 2014, Chemical Society reviews.

[64]  R. Langer,et al.  Skin permeabilization for transdermal drug delivery: recent advances and future prospects , 2014, Expert opinion on drug delivery.

[65]  Weitai Wu,et al.  Responsive materials for self-regulated insulin delivery. , 2013, Macromolecular bioscience.

[66]  S. Dhakate,et al.  Electrospun composite nanofiber-based transmucosal patch for anti-diabetic drug delivery. , 2013, Journal of materials chemistry. B.

[67]  N. Durán,et al.  Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system. , 2013, Journal of biomedical nanotechnology.

[68]  G. Wei,et al.  Oligoarginine-modified biodegradable nanoparticles improve the intestinal absorption of insulin. , 2013, International journal of pharmaceutics.

[69]  Daniel G Anderson,et al.  Injectable nano-network for glucose-mediated insulin delivery. , 2013, ACS nano.

[70]  Wei Wu,et al.  Nanoemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats , 2012, International journal of nanomedicine.

[71]  Ashish Jain,et al.  Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery , 2012, Journal of Nanoparticle Research.

[72]  A. Nayak,et al.  Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery. , 2012, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[73]  N. Zhang,et al.  Biodegradable solid lipid nanoparticle flocculates for pulmonary delivery of insulin. , 2012, Journal of biomedical nanotechnology.

[74]  F. Ahsan,et al.  PEG-PLGA based large porous particles for pulmonary delivery of a highly soluble drug, low molecular weight heparin. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[75]  H. Car,et al.  Nanoparticles as drug delivery systems , 2012, Pharmacological reports : PR.

[76]  Ying-zheng Zhao,et al.  Experiment on the feasibility of using modified gelatin nanoparticles as insulin pulmonary administration system for diabetes therapy , 2012, Acta Diabetologica.

[77]  J. Nie,et al.  Glucose-responsive insulin delivery microhydrogels from methacrylated dextran/concanavalin A: preparation and in vitro release study. , 2012, Carbohydrate polymers.

[78]  Chuanbin Wu,et al.  Insulin-Loaded pH-Sensitive Hyaluronic Acid Nanoparticles Enhance Transcellular Delivery , 2012, AAPS PharmSciTech.

[79]  C. Song,et al.  Preparation, characterization and in vivo evaluation of pH‐sensitive oral insulin‐loaded poly(lactic‐co‐glycolicacid) nanoparticles , 2012, Diabetes, obesity & metabolism.

[80]  Akira Matsumoto,et al.  A synthetic approach toward a self-regulated insulin delivery system. , 2012, Angewandte Chemie.

[81]  L. Lan,et al.  Glucose and Temperature Dual Stimuli Responsiveness of Intelligent Hollow Nanogels , 2012 .

[82]  T. Maekawa,et al.  POLYMERIC SCAFFOLDS IN TISSUE ENGINEERING APPLICATION: A REVIEW , 2011 .

[83]  Li Wang,et al.  Organization of glucose-responsive systems and their properties. , 2011, Chemical reviews.

[84]  S. Jose,et al.  Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation , 2011, Journal of advanced pharmaceutical technology & research.

[85]  F. Alexis,et al.  Stimulus responsive nanogels for drug delivery , 2011 .

[86]  H. Katsumi,et al.  Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats. , 2011, Journal of pharmaceutical sciences.

[87]  B. Sarmento,et al.  Chitosan-coated solid lipid nanoparticles enhance the oral absorption of insulin , 2011, Drug Delivery and Translational Research.

[88]  A. Badwan,et al.  Insulin-chitosan polyelectrolyte _anocomplexes: preparation, characterization and stabilization of insulin , 2010 .

[89]  H. Katsumi,et al.  Effects of polyamidoamine (PAMAM) dendrimers on the nasal absorption of poorly absorbable drugs in rats. , 2010, International journal of pharmaceutics.

[90]  Jorge F. J. Coelho,et al.  Temperature and pH responsive polymers based on chitosan: Applications and new graft copolymerization strategies based on living radical polymerization , 2010 .

[91]  Hsin‐Lung Chen,et al.  Enteric-coated capsules filled with freeze-dried chitosan/poly(gamma-glutamic acid) nanoparticles for oral insulin delivery. , 2010, Biomaterials.

[92]  A. Bajpai,et al.  Designing Gelatin Nanocarriers as a Swellable System for Controlled Release of Insulin: An In-Vitro Kinetic Study , 2009 .

[93]  Yongjun Zhang,et al.  Layer-by-layer multilayer films linked with reversible boronate ester bonds with glucose-sensitivity under physiological conditions , 2009 .

[94]  K. M. Lin,et al.  Multi-ion-crosslinked nanoparticles with pH-responsive characteristics for oral delivery of protein drugs. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[95]  P. Diwan,et al.  Effective insulin delivery using starch nanoparticles as a potential trans-nasal mucoadhesive carrier. , 2008, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[96]  B. Sarmento,et al.  Oral insulin delivery by means of solid lipid nanoparticles , 2007, International journal of nanomedicine.

[97]  P. Diwan,et al.  Effective oral delivery of insulin in animal models using vitamin B12-coated dextran nanoparticles. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[98]  Shenmin Zhang,et al.  Controlled release of insulin from PLGA nanoparticles embedded within PVA hydrogels , 2007, Journal of materials science. Materials in medicine.

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

[100]  B. Sarmento,et al.  Alginate/Chitosan Nanoparticles are Effective for Oral Insulin Delivery , 2007, Pharmaceutical Research.

[101]  M. Sastry,et al.  Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin , 2007, Pharmaceutical Research.

[102]  P. Diwan,et al.  A novel vitamin B12-nanosphere conjugate carrier system for peroral delivery of insulin. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[103]  P. Maincent,et al.  Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[104]  P. Diwan,et al.  Influence of microencapsulation method and peptide loading on formulation of poly(lactide-co-glycolide) insulin nanoparticles. , 2006, Die Pharmazie.

[105]  B. Sarmento,et al.  Development and Comparison of Different Nanoparticulate Polyelectrolyte Complexes as Insulin Carriers , 2006, International Journal of Peptide Research and Therapeutics.

[106]  K. Tam,et al.  Release kinetics of hydrophobic and hydrophilic model drugs from pluronic F127/poly(lactic acid) nanoparticles. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[107]  L. Brannon-Peppas,et al.  Nanoparticle and targeted systems for cancer therapy. , 2004, Advanced drug delivery reviews.

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

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

[110]  Qiang Zhang,et al.  Phospholipid deformable vesicles for buccal delivery of insulin. , 2002, Chemical & pharmaceutical bulletin.

[111]  Kinam Park,et al.  Glucose-Binding Property of Pegylated Concanavalin a , 2001, Pharmaceutical Research.

[112]  María J. Vicent,et al.  Smart Polymeric Nanocarriers for Drug Delivery , 2019, Smart Polymers and their Applications.

[113]  Yong Gan,et al.  Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery. , 2018, Biomaterials.

[114]  Pharmacologic Approaches to Glycemic Treatment : Standards of Medical Care in Diabetes d 2019 , 2018 .

[115]  Guohua Jiang,et al.  Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin. , 2017, Materials science & engineering. C, Materials for biological applications.

[116]  V. Kamboj,et al.  Poloxamers based nanocarriers for drug delivery system , 2015 .

[117]  Ting Ye,et al.  Synthesis and volume phase transition of concanavalin A-based glucose-responsive nanogels , 2014 .

[118]  Y. Zu,et al.  Preparation and characterization of chitosan-polyvinyl alcohol blend hydrogels for the controlled release of nano-insulin. , 2012, International journal of biological macromolecules.

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

[120]  J. Ying,et al.  Glucose-Sensitive Nanoparticles for Controlled Insulin Delivery , 2003 .

[121]  G. Cevc Transdermal Drug Delivery of Insulin with Ultradeformable Carriers , 2003, Clinical pharmacokinetics.