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Current Drug Targets


ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article (Mini-Review)

Nanotechnology Advanced Strategies for the Management of Diabetes Mellitus

Author(s): Amira Mohamed Mohsen*

Volume 20 , Issue 10 , 2019

Page: [995 - 1007] Pages: 13

DOI: 10.2174/1389450120666190307101642

Price: $65


Background: Medications currently available for the management of diabetes mellitus are inconvenient and have some limitations. Thus, investigations for novel approaches are needed to deliver and target antidiabetics safely to the site of action.

Objective: The present review emphasizes the limitations of conventional antidiabetics and provides the recent progresses of nanotechnology in the treatment of diabetes mellitus with a special highlight on the novel nanocarriers methodologies employed as antidiabetic drug delivery systems.

Method: The potential nanocarriers employed for the treatment of diabetes comprise liposomes, niosomes, self-nanoemulsifying drug delivery systems, polymeric nanoparticles, gold nanoparticles, dendrimers and micelles. Herbal nanomedicine has also emerged to be a promising way for adequate delivery of herbal compounds. Other nanotechnology approaches involve the usage of oral insulin, inhalable insulin, artificial pancreas, and nanopump.

Results: Nanocarriers have proved to lead a successful delivery of antidiabetic medications, aiming at drug targeting for enhanced efficacy and safety.

Conclusion: These innovative generations of drug delivery systems have important benefits over conventionally existing ones. The future of nanotechnology in the management of diabetes is still open with several prospects and will be of pronounced significance.

Keywords: Diabetes mellitus, nanotechnology, nanocarriers, antidiabetic, insulin, herbal nanomedicine.

Graphical Abstract
Veiseh O, Tang BC, Whitehead KA, Anderson DG, Langer R. Managing diabetes with nanomedicine: challenges and opportunities. Nat Rev Drug Discov 2015; 14(1): 45-57.
Arya AK, Kumar L, Pokharia D, Tripathi K. Applications of nano- technology in diabetes. Dig J Nanomater Biostruct 2008; 3(4): 221-5.
Li W, Yuan G, Pan Y, Wang C, Chen H. Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: A review. Front Pharmacol 2017; 8: 74.
Sowers JR, Lester MA. Diabetes and cardiovascular disease. Diabetes Care 1999; 22: C14.
Tierney L. Current medical diagnosis and treatment. New York: Lange Medical Books/McGraw-Hill 2002.
Alberti KGMM, Zimmet Pf. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 1998; 15(7): 539-53.
Group NDD. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 28(12): 1039-57.
Ross SA, Gulve EA, Wang M. Chemistry and biochemistry of type 2 diabetes. Chem Rev 2004; 104(3): 1255-82.
Mo R, Jiang T, Di J, Tai W, Gu Z. Emerging micro-and nanotechnology based synthetic approaches for insulin delivery. Chem Soc Rev 2014; 43(10): 3595-629.
Rai VK, Mishra N, Agrawal AK, Jain S, Yadav NP. Novel drug delivery system: an immense hope for diabetics. Drug Deliv 2016; 23(7): 2371-90.
Rotenstein LS, Kozak BM, Shivers JP, et al. The ideal diabetes therapy: what will it look like? How close are we? Clin Diabetes 2012; 30(2): 44-53.
Kokil GR, Veedu RN, Ramm GA, Prins JB, Parekh HS. Type 2 diabetes mellitus: limitations of conventional therapies and intervention with nucleic acid-based therapeutics. Chem Rev 2015; 115(11): 4719-43.
Sutradhar KB, Sumi CD. Implantable microchip: the futuristic controlled drug delivery system. Drug Deliv 2016; 23(1): 1-11.
Pradhan SK. Microsponges as the versatile tool for drug delivery system. Int J Res Pharm Chem 2011; 1(2): 243-58.
Schmid M-H, Korting H. Therapeutic progress with topical liposome drugs for skin disease. Adv Drug Deliv Rev 1996; 18(3): 335-42.
Kesharwani P, Gorain B, Low SY, et al. Nanotechnology based approaches for anti-diabetic drugs delivery. Diabetes Res Clin Pract 2017; 136: 52-77.
Kralj M, Pavelic K. Medicine on a small scale. EMBO Rep 2003; 4(11): 1008-12.
Logothetidis S. Nanotechnology in medicine: the medicine of tomorrow and nanomedicine. Hippokratia 2006; 10(1): 7-21.
Pickup JC, Zhi ZL, Khan F, Saxl T, Birch DJ. Nanomedicine and its potential in diabetes research and practice. Diabetes Metab Res Rev 2008; 24(8): 604-10.
Bratlie KM, York RL, Invernale MA, Langer R, Anderson DG. Materials for diabetes therapeutics. Adv Healthc Mater 2012; 1(3): 267-84.
Yetisen AK, Montelongo Y, da Cruz Vasconcellos F, et al. Reusable, robust, and accurate laser-generated photonic nanosensor. Nano Lett 2014; 14(6): 3587-93.
Veetil JV, Jin S, Ye K. A glucose sensor protein for continuous glucose monitoring. Biosens Bioelectron 2010; 26(4): 1650-5.
Ravaine V, Ancla C, Catargi B. Chemically controlled closed-loop insulin delivery. J Control Release 2008; 132(1): 2-11.
Harsoliya M. Recent advances & applications of nanotechnology in diabetes. Int J Pharm Biol Arch 2012; 3(2)
Rajalakshmi A. Impact of nanotechnology in diabetes. Bull Env Pharmacol Life Sci 2014; 3: 1-4.
Gupta R. Diabetes treatment by nanotechnology. J Biotechnol Biomater 2017; 7(268): 2.
Desai TA, Chu WH, Tu JK, et al. Microfabricated immunoisolating biocapsules. Biotechnol Bioeng 1998; 57(1): 118-20.
Freitas RA. The future of nanofabrication and molecular scale devices in nanomedicine. Stud Health Technol Inform 2002; 80: 45-60.
Wu Z-H, Ping Q-N, Wei Y, Lai J. Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice. Acta Pharmacol Sin 2004; 25(7): 966-72.
Shalaby TI, El-Refaie WM. Bioadhesive chitosan-coated cationic nanoliposomes with improved insulin encapsulation and prolonged oral hypoglycemic effect in diabetic mice. J Pharm Sci 2018; 107(8): 2136-43.
Niu M, Lu Y, Hovgaard L, Wu W. Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation. Int J Nanomedicine 2011; 6: 1155-66.
Niu M, Lu Y, Hovgaard L, et al. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose. Eur J Pharm Biopharm 2012; 81(2): 265-72.
Hu S, Niu M, Hu F, et al. Integrity and stability of oral liposomes containing bile salts studied in simulated and ex vivo gastrointestinal media. Int J Pharm 2013; 441(1): 693-700.
Zhang X, Qi J, Lu Y, et al. Enhanced hypoglycemic effect of biotin-modified liposomes loading insulin: effect of formulation variables, intracellular trafficking, and cytotoxicity. Nanoscale Res Lett 2014; 9(1): 185.
Zhang X, Qi J, Lu Y, et al. Biotinylated liposomes as potential carriers for the oral delivery of insulin. Nanomed Nanotechnol 2014; 10(1): 167-76.
Moghassemi S, Parnian E, Hakamivala A, et al. Uptake and transport of insulin across intestinal membrane model using trimethyl chitosan coated insulin niosomes. Mater Sci Eng C 2015; 46: 333-40.
Pardakhty A, Varshosaz J, Rouholamini A. In vitro study of polyoxy- ethylene alkyl ether niosomes for delivery of insulin. Int J Pharm 2007; 328(2): 130-41.
Ning M, Guo Y, Pan H, Yu H, Gu Z. Niosomes with sorbitan monoester as a carrier for vaginal delivery of insulin: studies in rats. Drug Deliv 2005; 12(6): 399-407.
Sarmento B, Martins S, Ferreira D, Souto EB. Oral insulin delivery by means of solid lipid nanoparticles. Int J Nanomedicine 2007; 2(4): 743-9.
Fonte P, Nogueira T, Gehm C, Ferreira D, Sarmento B. Chitosan-coated solid lipid nanoparticles enhance the oral absorption of insulin. Drug Deliv Transl Res 2011; 1(4): 299-308.
Gu Z, Aimetti AA, Wang Q, et al. Injectable nano-network for glucose-mediated insulin delivery. ACS Nano 2013; 7(5): 4194-201.
Sheng J, He H, Han L, et al. Enhancing insulin oral absorption by using mucoadhesive nanoparticles loaded with LMWP-linked insulin conjugates. J Control Release 2016; 233: 181-90.
Malathi S, Nandhakumar P, Pandiyan V, Webster TJ, Balasubramanian S. Novel PLGA-based nanoparticles for the oral delivery of insulin. Int J Nanomedicine 2015; 10: 2207-18.
Li X, Wu W, Li J. Glucose-responsive micelles for insulin release. J Control Release 2015; 213: e122-3.
Dong Z, Hamid KA, Gao Y, et al. Polyamidoamine dendrimers can improve the pulmonary absorption of insulin and calcitonin in rats. J Pharm Sci 2011; 100(5): 1866-78.
Nowacka O, Milowska K, Belica-Pacha S, et al. Generation-dependent effect of PAMAM dendrimers on human insulin fibrillation and thermal stability. Int J Biol Macromol 2016; 82: 54-60.
Nowacka O, Shcharbin D, Klajnert-Maculewicz B, Bryszewska M. Stabilizing effect of small concentrations of PAMAM dendrimers at the insulin aggregation. Colloids Surf B 2014; 116: 757-60.
Fang X, Yang T, Wang L, et al. Nano-cage-mediated refolding of insulin by PEG-PE micelle. Biomaterials 2016; 77: 139-48.
Subash Chandran M, Pandey V. In-vitro and in-vivo evaluation of glimepiride loaded liposomes. Der Pharma Chem 2016; 8(24): 22-6.
Mohsen AM, AbouSamra MM, ElShebiney SA. Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation. Drug Dev Ind Pharm 2017; 1-11.
Mohd AB, Sanka K, Bandi S, Diwan PV, Shastri N. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits. Drug Deliv 2015; 22(4): 499-508.
Tamizharasi S, Dubey A, Rathi V, Rathi J. Development and characterization of niosomal drug delivery of gliclazide. J Young Pharm 2009; 1(3): 205.
Dash RN, Mohammed H, Humaira T, Ramesh D. Design, optimization and evaluation of glipizide solid self-nanoemulsifying drug delivery for enhanced solubility and dissolution. Saudi Pharm J 2015; 23(5): 528-40.
Karthick V, Kumar VG, Dhas TS, et al. Effect of biologically synthesized gold nanoparticles on alloxan-induced diabetic rats-an in vivo approach. Colloids Surf B 2014; 122: 505-11.
Shaheen TI, El-Naggar ME, Hussein JS, et al. Antidiabetic assessment; in vivo study of gold and core-shell silver-gold nanoparticles on streptozotocin-induced diabetic rats. Biomed Pharmacother 2016; 83: 865-75.
Pandita D, Kumari N, Lather V. A Self-nanoemulsifying Drug delivery system for poorly water soluble tolbutamide: development, optimization and pharmacodynamic studies. Pharm Nanotechnol 2017; 5(4): 285-300.
Namdev S, Gujar K, Mandlik S, Jamkar P. Preparation and in vivo characterization of niosomal carriers of the antidiabetic drug repaglinide. IJPSN 2015; 8(1): 2756-67.
Ebrahimi HA, Javadzadeh Y, Hamidi M, Jalali MB. Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles. DARU J Pharm Sci 2015; 23(1): 46.
Kassem A. SH AE-A, Basha M, Salama A. Phospholipid complex enriched micelles: A novel drug delivery approach for promoting the antidiabetic effect of repaglinide. Eur J Pharm Sci 2017; 99: 75-84.
Haider M, Kanoujia J, Tripathi CB, et al. Pioglitazone loaded vesicular carriers for anti-diabetic activity: development and optimization as per central composite design. J Pharm Sci Pharmacol 2015; 2(1): 11-20.
Manconi M, Nácher A, Merino V, et al. Improving oral bioavailability and pharmacokinetics of liposomal metformin by glycerolphosphate–chitosan microcomplexation. AAPS PharmSciTech 2013; 14(2): 485-96.
Sankhyan A, Pawar PK. Metformin loaded non-ionic surfactant vesicles: optimization of formulation, effect of process variables and characterization. DARU J Pharm Sci 2013; 21(1): 7.
Hasan AA, Madkor H, Wageh S. Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system. Drug Deliv 2013; 20(3-4): 120-6.
Xu Q, Zhu T, Yi C, Shen Q. Characterization and evaluation of metformin-loaded solid lipid nanoparticles for celluar and mitochondrial uptake. Drug Dev Ind Pharm 2016; 42(5): 701-6.
Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett 2013; 8(1): 102.
Goyal P, Goyal K, Kumar SGV, et al. Liposomal drug delivery systems-clinical applications. Acta Pharm 2005; 55(1): 1-25.
Mohsen AM, Asfour MH, Salama AA. Improved hepatoprotective activity of silymarin via encapsulation in the novel vesicular nanosystem bilosomes. Drug Dev Ind Pharm 2017; 43(12): 2043-54.
Thurston G, McLean JW, Rizen M, et al. Cationic liposomes target angiogenic endothelial cells in tumors and chronic inflammation in mice. J Clin Invest 1998; 101(7): 1401-13.
Lim HJ, Cho EC, Shim J, et al. Polymer-associated liposomes as a novel delivery system for cyclodextrin-bound drugs. J Colloid Interface Sci 2008; 320(2): 460-8.
Agrawal AK, Harde H, Thanki K, Jain S. Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration. Biomacromol 2013; 15(1): 350-60.
Khan R, Irchhaiya R. Niosomes: a potential tool for novel drug delivery. J Pharm Investig 2016; 46(3): 195-204.
Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes): physical and pharmaceutical chemistry. Adv Colloid Interface Sci 1995; 58(1): 1-55.
El-Ridy MS, Yehia SA, Mohsen AM, El-Awdan SA, Darwish AB. Formulation of Niosomal Gel for Enhanced Transdermal Lornoxicam Delivery: In-Vitro and In-Vivo Evaluation. Curr Drug Deliv 2018; 15(1): 122-33.
El-Ridy MS, Badawi AA, Safar MM, Mohsen AM. Niosomes as a novel pharmaceutical formulation encapsulating the hepatoprotective drug silymarin. Int J Pharm Pharm Sci 2012; 4(1): 549-59.
Lohumi A. A novel drug delivery system: niosomes review. J Drug Deliv Ther 2012; 2(5)
NVS M, Saini A. Niosomes: a novel drug delivery system. Int J Res Pharm Chem 2011; 1: 498-511.
Kazi KM, Mandal AS, Biswas N, et al. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res 2010; 1(4): 374.
Shirsand S, Para M, Nagendrakumar D, Kanani K, Keerthy D. Formulation and evaluation of Ketoconazole niosomal gel drug delivery system. Int J Pharm Investig 2012; 2(4): 201.
Chandra S, Venu V, Jaganathan K, Perumal P. Formulation and in vitro evaluation of sustained release matrix tablets of glimepiride by using natural gums as release modifiers. J Glob Trends Pharm Sci 2011; 2(4): 394-403.
Azeem A, Anwer MK, Talegaonkar S. Niosomes in sustained and targeted drug delivery: some recent advances. J Drug Target 2009; 17(9): 671-89.
ElMeshad AN, Mohsen AM. Enhanced corneal permeation and antimycotic activity of itraconazole against Candida albicans via a novel nanosystem vesicle. Drug Deliv 2016; 23(7): 2115-23.
Alam MS, Ahad A, Abidin L, et al. Embelin-loaded oral niosomes ameliorate streptozotocin-induced diabetes in Wistar rats. Biomed Pharmacother 2018; 97: 1514-20.
Sultan AA, El-Gizawy SA, Osman MA, El Maghraby GM. Niosomes for oral delivery of nateglinide: in situ-in vivo correlation. J Liposome Res 2018; 28(3): 209-17.
Singh B, Singh R, Bandyopadhyay S, Kapil R, Garg B. Optimized nanoemulsifying systems with enhanced bioavailability of carvedilol. Colloids Surf B 2013; 101: 465-74.
Porter CJ, Pouton CW, Cuine JF, Charman WN. Enhancing intestinal drug solubilisation using lipid-based delivery systems. Adv Drug Deliv Rev 2008; 60(6): 673-91.
Hu X, Lin C, Chen D, et al. Sirolimus solid self-microemulsifying pellets: formulation development, characterization and bioavailability evaluation. Int J Pharm 2012; 438(1-2): 123-33.
Setthacheewakul S, Mahattanadul S, Phadoongsombut N, Pichayakorn W, Wiwattanapatapee R. Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats. Eur J Pharm Biopharm 2010; 76(3): 475-85.
Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res 1995; 12(11): 1561-72.
Balakumar K, Raghavan CV, Abdu S. Self nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin calcium: design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf B 2013; 112: 337-43.
Kassem AA, Mohsen AM, Ahmed RS, Essam TM. Self-nanoemulsi- fying drug delivery system (SNEDDS) with enhanced solubilization of nystatin for treatment of oral candidiasis: Design, optimization, in vitro and in vivo evaluation. J Mol Liq 2016; 218: 219-32.
Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Deliv Rev 1997; 25(1): 47-58.
Date AA, Nagarsenker M. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int J Pharm 2007; 329(1-2): 166-72.
Rashid M, Wani TU, Mishra N, et al. Development and characterization of drug-loaded self-solid nano-emulsified drug delivery system for treatment of diabetes Mat Sci Res India 2018; 15(1): 01- 11.
Wu D-Y, Ma Y, Hou X-S, et al. Co-delivery of antineoplastic and protein drugs by chitosan nanocapsules for a collaborative tumor treatment. Carbohydr Polym 2017; 157: 1470-8.
Wilczewska AZ, Niemirowicz K, Markiewicz KH, Car H. Nano- particles as drug delivery systems. Pharmacol Rep 2012; 64(5): 1020-37.
Liu Z, Jiao Y, Wang Y, Zhou C, Zhang Z. Polysaccharides-based nanoparticles as drug delivery systems. Adv Drug Deliv Rev 2008; 60(15): 1650-62.
Abousamra Mm, Mohsen Am. Solid lipid nanoparticles and nanostructured lipid carriers of tolnaftate: design, optimization and in-vitro evaluation. Int J Pharm Pharm Sci 2016; 8(1): 380-5.
Asfour MH, Mohsen AM. Formulation and evaluation of pH-sensitive rutin nanospheres against colon carcinoma using HCT-116 cell line. J Adv Res 2018; 9: 17-26.
De Jong WH, Borm PJ. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine 2008; 3(2): 133.
Chan JM, Valencia PM, Zhang L, Langer R, Farokhzad OC. Polymeric nanoparticles for drug delivery. Cancer Nanotechnol 2010; 163-75.
Sona P. Nanoparticulate drug delivery systems for the treatment of diabetes. Dig J Nanomater Biostruct 2010; 5(2)
Sgorla D, Lechanteur A, Almeida A, et al. Development and characterization of lipid-polymeric nanoparticles for oral insulin delivery. Expert Opin Drug Deliv 2018; 15(3): 213-22.
Brown SD, Nativo P, Smith J-A, et al. Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin. J Am Chem Soc 2010; 132(13): 4678-84.
Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram E. The insulinotropic activity of Gymnema sylvestre, R. Br. An Indian medical herb used in controlling diabetes mellitus. Pharmacol Res Commun 1981; 13(5): 475-86.
Edrees HM, Elbehiry A, Elmosaad YM. Hypoglycemic and anti-inflammatory effect of gold nanoparticles in streptozotocin-induced type 1 diabetes in experimental rats. Int J Diabetes Res 2017; 6(1): 16-23.
Sengani M. Identification of potential antioxidant indices by biogenic gold nanoparticles in hyperglycemic Wistar rats. ‎. Environ Toxicol Pharmacol 2017; 50: 11-9.
Abbasi E, Aval SF, Akbarzadeh A, et al. Dendrimers: synthesis, applications, and properties. Nanoscale Res Lett 2014; 9(1): 247.
Baig T, Nayak J, Dwivedi V, et al. A review about dendrimers: Synthesis, types, characterization and applications. Int J Adv Pharm Biol Chem 2015; 2015: 44-59.
Chaudhari HS, Popat RR, Adhao VS, Shrikhande VN. Dendrimers: Novel carriers for drug delivery. JAPTRonline 2016; 4(1): 01-19.
Dwivedi N, Shah J, Mishra V, et al. Dendrimer-mediated approaches for the treatment of brain tumor. J Biomater Sci Polym Ed 2016; 27(7): 557-80.
Gorain B, Tekade M, Kesharwani P, et al. The use of nanoscaffolds and dendrimers in tissue engineering. Drug Discov Today 2017; 22(4): 652-64.
Gupta U, Agashe HB, Asthana A, Jain NK. A review of in vitro-in vivo investigations on dendrimers: the novel nanoscopic drug carriers. Nanomed Nanotechnol 2006; 2(2): 66-73.
Fangueiro JF, Silva AM, Garcia ML, Souto EB. Current nanotechnology approaches for the treatment and management of diabetic retinopathy. Eur J Pharm Biopharm 2015; 95: 307-22.
Cloninger MJ. Biological applications of dendrimers. Curr Opin Chem Biol 2002; 6(6): 742-8.
Jones M-C, Leroux J-C. Polymeric micelles-a new generation of colloidal drug carriers. Eur J Pharm Biopharm 1999; 48(2): 101-11.
Ahmad Z, Shah A, Siddiq M, Kraatz H-B. Polymeric micelles as drug delivery vehicles. Rsc Adv 2014; 4(33): 17028-38.
Liao C, Chen Y, Yao Y, et al. Cross-linked small-molecule micelle-based drug delivery system: concept, synthesis, and biological evaluation. Chem Mater 2016; 28(21): 7757-64.
Seow WY, Xue JM, Yang Y-Y. Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles. Biomaterials 2007; 28(9): 1730-40.
Andrade F, Fonte P, Costa A, et al. Pharmacological and toxicological assessment of innovative self-assembled polymeric micelles as powders for insulin pulmonary delivery. Nanomedicine 2016; 11(17): 2305-17.
Gopi S, Amalraj A, Haponiuk J, Thomas S. Introduction of nanotechnology in herbal drugs and nutraceutical: A Review. J Nanomedine Biotherapeutic Discov 2016; 6: 2.
Van Lerberghe W. The world health report 2008: primary health care: now more than ever: World Health Organization; 2008.
Rani R, Dahiya S, Dhingra D, et al. Improvement of antihyperglycemic activity of nano-thymoquinone in rat model of type-2 diabetes. Chem Biol Interact 2018; 295: 119-32.
Bitencourt PE, Ferreira LM, Cargnelutti LO, et al. A new biodegradable polymeric nanoparticle formulation containing Syzygium cumini: Phytochemical profile, antioxidant and antifungal activity and in vivo toxicity. Ind Crops Prod 2016; 83: 400-7.
Venkatachalam M, Govindaraju K, Sadiq AM, et al. Functionalization of gold nanoparticles as antidiabetic nanomaterial. Spectrochim Acta A Mol Biomol Spectrosc 2013; 116: 331-8.
Shanker K, Mohan GK, Hussain MA, Jayarambabu N, Pravallika PL. Green biosynthesis, characterization, in vitro antidiabetic activity, and investigational acute toxicity studies of some herbal-mediated silver nanoparticles on animal models. Pharmacogn Mag 2017; 13(49): 188.
Shanker K, Naradala J, Mohan GK, Kumar G, Pravallika P. A sub-acute oral toxicity analysis and comparative in vivo anti-diabetic activity of zinc oxide, cerium oxide, silver nanoparticles, and Momordica charantia in streptozotocin-induced diabetic Wistar rats. Rsc Adv 2017; 7(59): 37158-67.
Prabhu S, Vinodhini S, Elanchezhiyan C, Rajeswari D. Evaluation of antidiabetic activity of biologically synthesized silver nanoparticles using Pouteria sapota in streptozotocin induced diabetic rats. J Diabetes 2018; 10(1): 28-42.
Malapermal V, Botha I, Krishna SBN, Mbatha JN. Enhancing antidiabetic and antimicrobial performance of Ocimum basilicum, and Ocimum sanctum (L.) using silver nanoparticles. Saudi J Biol Sci 2017; 24(6): 1294-305.
Swarnalatha L, Rachela C, Ranjan P, Baradwaj P. Evaluation of in vitro antidiabetic activity of Sphaeranthus amaranthoides silver nanoparticles. Int J Nanomater Biostruct 2012; 2(3): 25-9.
Langle A, González-Coronel MA, Carmona-Gutiérrez G, et al. Stevia rebaudiana loaded titanium oxide nanomaterials as an antidiabetic agent in rats. Rev Bras Farmacogn 2015; 25(2): 145-51.
Bindu RH, Lakshmi SM, Himaja N, Nirosha K, Pooja M. Formulation, characterisation and anti diabetic evaluation of talinum portulacifolium (forssk.) loaded solid lipid nanoparticles in streptozotocin & high fat diet induced diabetic rats. J Glob Trends Pharm Sci 2014; 5: 2108-14.
Kavitha K, Sujatha K, Manoharan S. Development, characterization and antidiabetic potentials of nilgirianthus ciliatus nees derived nanoparticles. J Nanomedine Biotherapeutic Discov 2017; 7(2)
Krauland AH, Guggi D, Bernkop-Schnürch A. Oral insulin delivery: the potential of thiolated chitosan-insulin tablets on non-diabetic rats. J Control Release 2004; 95(3): 547-55.
Borchard G, Lueßen HL, de Boer AG, et al. The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III: Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro. J Control Release 1996; 39(2-3): 131-8.
Ward PD, Tippin TK, Thakker DR. Enhancing paracellular permeability by modulating epithelial tight junctions. Pharm Sci Technol Today 2000; 3(10): 346-58.
Patel HM, Ryman BE. Orally Administered liposomally entrapped insulin. Biochem Soc Trans 1977; 5(6): 1739-41.
Damgé C, Michel C, Aprahamian M, Couvreur P. New approach for oral administration of insulin with polyalkylcyanoacrylate nanocapsules as drug carrier. Diabetes 1988; 37(2): 246-51.
Damgé C, Maincent P, Ubrich N. Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. J Control Release 2007; 117(2): 163-70.
Lin Y-H, Chen C-T, Liang H-F, et al. Novel nanoparticles for oral insulin delivery via the paracellular pathway. Nanotechnology 2007; 18(10)105102
Jindal SK, Singh M, Goswami M. Formulation and evaluation of insulin enteric microspheres for oral drug delivery. Acta Pharm Sci 2009; 51: 121-7.
Woldu MA, Lenjisa JL. Nanoparticles and the new era in diabetes management. Int J Basic Clin Pharmacol 2014; 3(2): 277-84.
Moghimi SM, Hunter AC, Murray JC. Nanomedicine: current status and future prospects. FASEB J 2005; 19(3): 311-30.
Hanazaki K, Nosé Y, Brunicardi FC. Artificial endocrine pancreas. J Am Coll Surg 2001; 193(3): 310-22.
Subramani K, Pathak S, Hosseinkhani H. Recent trends in diabetes treatment using nanotechnology. Dig J Nanomater Biostruct 2012; 7(1): 85-95.
Rahiman S, Tantry BA. Nanomedicine current trends in diabetes management. J Nanomed Nanotechnol 2012; 3(5)

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