Nanoformulation mediated transdermal delivery of anti-diabetic drugs: an updated review

Abstract

Diabetes mellitus is a concern of disorder globally and which is increasing continuously. Diabetic complications lead to physical, mental and societal issues to patients. Oral medications are being prescribed but these have problems like frequent dosing, side effects and non-patient compliance. Insulin therapy is also problematic due to injectable route of delivery. Dose missing of these treatments lead to fluctuations in blood glucose levels which cause severe adverse effects. Recent developments have shown the potential of transdermal drug administration in association with nanoformulations for improving the efficacy and safety of anti-diabetic medications. Nanotechnology offers modification of size and surface characteristics of nanocarriers which enhances the drug permeation through biological barriers. Transdermal drug delivery in conjunction with nanocarriers provide enhanced permeation, improved bioavailability and sustained effect with reduction in adverse effects. This article first presents the current scenarios of diabetes mellitus and important aspects of transdermal drug delivery systems. In later sections, a detailed description (pharmaceutical and preclinical characteristics) of various nanoformulation assisted transdermal drug delivery systems (polymeric nanoparticles, ethosomes, nanostructured lipid carriers, solid lipid nanoparticles, microemulsions, liposomes, niosomes, nanoemulsions, transethosomes and transfersomes) have been reviewed. Transdermal drug delivery in conjunction with nanoformulations can be utilized for the better management and control of diabetes.

Keywords

Transdermal drug delivery / Anti-diabetic / Nanoformulations / Liposomes / Nanoparticles / Ethosomes

References

[1] Zhang Y , Yu J , Kahkoska AR , Wang J , Buse JB , Gu Z . Advances in transdermal insulin delivery. Adv Drug Deliv Rev. 2019; 139: 51- 70.

[2] Srinivasan S , Elumalai K , Cherian BV , Ramanujam SK . Formulation and characterization of metformin hydrochloride orodispersible tablets with super disintegrants. Intelligent Pharm. 2023. https://doi.org/10.1016/j.ipha.2023.06.006.

[3] Ng LC , Gupta M . Transdermal drug delivery systems in diabetes management: a review. Asian J Pharm Sci. 2020; 15 (1): 13- 25.

[4] Singh S , Kushwaha P , Gupta SK . Exploring the potential of traditional herbs in the management of diabetic retinopathy: an overview. Drug Res. 2020; 70 (7): 298- 309.

[5] Shamim A , Siddiqui HH , Mahmood T , Bagga P , Kumar R . A comprehensive study on literature evidence, clinical studies and practices of herbal drugs for diabetic neuropathy and cardiomyopathy. Asian J Pharm Clin Res. 2017; 10 (9): 30- 37.

[6] Sabbagh F , Muhamad II , Niazmand R , Dikshit PK , Kim BS . Recent progress in polymeric non-invasive insulin delivery. Int J Biol Macromol. 2022; 203: 222- 243.

[7] Sabbagh F , Kim BS . Recent advances in polymeric transdermal drug delivery systems. J Contr Release. 2022; 341: 132- 146.

[8] Zhao R , Lu Z , Yang J , Zhang L , Li Y , Zhang X . Drug delivery system in the treatment of diabetes mellitus. Front Bioeng Biotechnol. 2020; 8: 880.

[9] Panwar R , Raghuwanshi N , Srivastava AK , Sharma AK , Pruthi V . In-vivo sustained release of nanoencapsulated ferulic acid and its impact in induced diabetes. Mater Sci Eng C Mater Biol Appl. 2018; 92: 381- 392.

[10] Chen X , Ren Y , Feng Y , Xu X , Tan H , Li J . Cp1-11 peptide/insulin complex loaded pHresponsive nanoparticles with enhanced oral bioactivity. Int J Pharm. 2019; 562: 23- 30.

[11] Garg V , Kaur P , Gulati M , et al. Coadministration of polypeptide-k and curcumin through solid self-nanoemulsifying drug delivery system for better therapeutic effect against diabetes mellitus: formulation, optimization, biopharmaceutical characterization, and pharmacodynamic assessment. Assay Drug Dev Technol. 2019; 17 (4): 201- 221.

[12] Xu HY , Liu CS , Huang CL , et al. Nanoemulsion improves hypoglycemic efficacy of berberine by overcoming its gastrointestinal challenge. Colloids Surf B Biointerfaces. 2019; 181: 927- 934.

[13] Mohseni R , ArabSadeghabadi Z , Ziamajidi N , Abbasalipourkabir R , RezaeiFarimani A . Oral administration of resveratrol-loaded solid lipid nanoparticle improves insulin resistance through targeting expression of SNARE proteins in adipose and muscle tissue in rats with type 2 diabetes. Nanoscale Res Lett. 2019; 14 (1): 227.

[14] Piazzini V , Micheli L , Luceri C , et al. Nanostructured lipid carriers for oral delivery of silymarin: improving its absorption and in vivo efficacy in type 2 diabetes and metabolic syndrome model. Int J Pharm. 2019; 572: 118838.

[15] Amjadi S , Mesgari Abbasi M , Shokouhi B , Ghorbani M , Hamishehkar H . Enhancement of therapeutic efficacy of betanin for diabetes treatment by liposomal nanocarriers. J Funct Foods. 2019; 59: 119- 128.

[16] Suzuki K , Kim KS , Bae YH . Long-term oral administration of Exendin-4 to control type 2 diabetes in a rat model. J Contr Release. 28;294:259-267..

[17] Gouda W , Hafiz NA , Mageed L , Alazzouni AS , Khalil WKB , Abdelmaksoud MDE . Effects of nano-curcumin on gene expression of insulin and insulin receptor. Bull Natl Res Cent. 2019; 43: 128.

[18] Zhao X , Wang W , Zu Y , et al. Preparation and characterization of betulin nanoparticles for oral hypoglycemic drug by antisolvent precipitation. Drug Deliv. 2014; 21 (6): 467- 479.

[19] Mamatha T , Zubair M , Begum S , Muneera T . Various emerging trends in insulin drug delivery systems. Br J Pharmaceut Res. 2015; 5 (5): 294- 308.

[20] Anhalt H , Bohannon NJ . Insulin patch pump: their development and future in closedloop systems. Diabetes Technol Ther. 2010;12(s1):5–51.

[21] Ali Asad , Ahmad Usama . Nanoemulsion as a vehicle in transdermal drug delivery. Insights Biomed. 2018; 3: 2572- 5610.

[22] Rastogi V , Yadav P . Transdermal drug delivery system: an overview. Asian J Pharm. 2014; 6 (3): 16.

[23] Alkilani AZ , McCrudden MT , Donnelly RF . Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015; 7 (4): 438- 470.

[24] Naik A , Kalia YN , Guy RH . Transdermal drug delivery: overcoming the skin's barrier function. Pharm Sci Technol Today. 2000; 3 (9): 318- 326.

[25] Keleb E , Sharma RK , Mosa EB , Aljahwi AA . Transdermal drug delivery system design and evaluation. Int J Adv Pharm. 2010;1(3).

[26] Shariq M , Mahmood T , Kushwaha P , et al. Fabrication of nanoformulation containing carvedilol and silk protein sericin against doxorubicin induced cardiac damage in rats. Pharmaceuticals. 2023; 16: 561.

[27] Zielińska A , Carreiró F , Oliveira AM , et al. Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology. Molecules. 2020; 25 (16): 3731.

[28] Behin SR , Punitha IS , Saju F . Development of matrix dispersion transdermal therapeutic system containing glipizide. Der Pharm Lett. 2013; 5 (3): 278- 286.

[29] Jaimini M , Tiwari R , Sharma SK , Chauhan BS , Mohan S . Formulation and in-vitro evaluation of transdermal film of gliclazide for type II diabetes mellitus. Int J Pharm Sci. 2013; 4 (2): 339- 343.

[30] Zhang Y , Jiang G , Hong W , et al. Polymeric microneedles integrated with metforminloaded and PDA/LA-Coated hollow mesoporous SiO2 for NIR-triggered transdermal delivery on diabetic rats. ACS Appl Bio Mater. 2018; 1 (6): 1906- 1917.

[31] Verma P , Pathak K . Therapeutic and cosmeceutical potential of ethosomes: an overview. J Adv Pharm Technol Res. 2010; 1 (3): 274- 282, 3.

[32] Bodade SS , Shaikh KS , Kamble MS , Chaudhari PD . A study on ethosomes as mode for transdermal delivery of an antidiabetic drug. Drug Deliv. 2013; 20 (1): 40- 46.

[33] Tiwari A , Mishra MK , Shukla A . Formulation and evaluation of anti-diabetic ethosome. Br J Biomed. 2018; 2: 289- 299.

[34] Wahid AA , Ravouru N . Development, characterization and in-vitro evaluation of ethosomal gel for transdermal delivery of saxagliptin. J Glob Trends Pharm Sci. 2017; 8 (4): 4429- 4437.

[35] Aouta EK , Patra CN . Design, optimization and characterization of combined ethosomal transdermal patch of glimepiride and duloxetine drug regimen for diabetes and associated neuropathic pain management. Curr Drug Ther. 2022; 17 (5): 359- 368.

[36] Chauhan I , Yasir M , Verma M , Singh AP . Nanostructured lipid carriers: a groundbreaking approach for transdermal drug delivery. Adv Pharm Bull. 2020: 150- 165.

[37] Sohrab A , Mohammed A , Khan A , et al. Nanostructured lipid carriers of pioglitazone for transdermal application: from experimental design to bioactivity detail. Drug Deliv. 2016; 23 (2): 601- 609.

[38] Kesharwani R , Patel D , Yadav PK . Bioavailability enhancement of repaglinide using nano lipid carrier: preparation characterization and in vivo evaluation. Int J Appl Pharm. 2022; 14 (5): 181- 189.

[39] Jahan S , Aqil M , Ahad A , et al. Nanostructured lipid carrier for transdermal gliclazide delivery: development and optimization by box-behnken design. Inorg Nano-Met Chem. 2022;(2):1556–2470.

[40] Mehnert W , Mader K . Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2–3):165–196.

[41] Sharma RK , Sharma N , Rana S , Shivkumar HG . Solid lipid nanoparticles as a carrier of metformin for transdermal delivery. Int J Drug Deliv. 5(2):137–145..

[42] Vijayan V , Jayachandran E , Anburaj J , Rao DS , Vijayan KJK . Transdermal delivery of repaglinide from solid lipid nanoparticles in diabetic rats: in vitro and in vivo studies. J Pharm Sci Res. 2011; 3 (3): 1077- 1081.

[43] Jahan L , Ferdaus R , Shaheen SM , Sultan MZ , Mazid MA . In vitro transdermal delivery of metformin from an HPMC/PVA based TDS-patch at different pH. J Sci Res. 2011; 3 (3): 651- 657.

[44] Elbahwy IA , Ibrahim HM , Ismael HR , Kasem AA . Enhancing bioavailability and controlling the release of glibenclamide from optimized solid lipid nanoparticles. J Drug Deliv Sci Technol. 2017; 38: 78- 89.

[45] Vidya S , Sejal V . Formulation and evaluation of microemulsion-based hydrogel for topical delivery. Int J Pharm Investig. 2012; 2 (3): 140- 149, 3.

[46] Singh MK , Chandel V , Gupta V , Ramteke S . Formulation development and characterization of microemulsion for topical delivery of glipizide. Der Pharm Lett. 2010; 2 (3): 33- 42.

[47] Shinde UA , Modani SH , Singh KH . Design and development of repaglinide microemulsion gel for transdermal delivery. AAPS PharmSciTech. 2018;(1):315–325.

[48] Madikattu K , Kalamata VN , Srisailam K . Enhanced bioavailability of glimepiride through microemulsion based transdermal gels. Int J Pharm Sci Res. 2016; 7 (12): 5052- 5055.

[49] Islam MR , Uddin S , Chowdhury MR , Wakabayashi R , Moniruzzaman M , Goto M . Insulin transdermal delivery system for diabetes treatment using a biocompatible ionic liquid-based microemulsion. ACS Appl Mater Interfaces. 2021; 13 (36): 42461- 42472.

[50] Claudia Z , Sandro M . Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape. Drug Deliv. 2016; 9: 1- 11.

[51] Joshi S , Hussain MT , Roces CB , et al. Microfluidics based manufacture of liposomes simultaneously entrapping hydrophilic and lipophilic drugs. Int J Pharm. 2016; 514(1).

[52] Mohamed B , Nadia A , Basmah A , Ahlam A , Amal E . Transdermal glipizide delivery system based on chitosan-coated deformable liposomes: development, ex vivo, and in vivo studies. Pharmaceutics. 2022; 14 (4): 826.

[53] Ahmed OAA , Kurakula M , Banjar ZM , Afouna MI , Zidan AS . Quality by design coupled with near infrared in formulation of transdermal glimepiride liposomal films. J Pharm Sci. 2015; 104 (6): 2062- 2075.

[54] Kazi KM , Mandal AS , Biswas N , et al. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010;(4):374–380.

[55] 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; 8: 1254- 1264.

[56] Prasad PS , Imam SS , Sultana Y , Ali A . QbD-based Carbopol transgel formulation: characterization, pharmacokinetic assessment and therapeutic efficacy in diabetes. Drug Deliv. 2016; 23 (3): 1057- 1066.

[57] El-Ridy MS , Yehia SA , El-Sayed I , Younis MM , Rahman RFA , El-Gamil MA . Metformin hydrochloride and wound healing: from nanoformulation to pharmacological evaluation. J Liposome Res. 2019; 29 (4): 343- 356.

[58] Shehata TM , Nair AB , Al-Dhubiab BE , et al. Vesicular emulgel based system for transdermal delivery of insulin: factorial design and in vivo evaluation. Appl Sci. 2020; 10 (15): 5341.

[59] Jaiswal M , Dudhe R , Sharma PK . Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2015; 5 (2): 123- 127.

[60] Akhtar J , Siddiqui HH , Fareed S , Badruddeen Khalid M , Aqil M . Nanoemulsion: for improved oral delivery of repaglinide. Drug Deliv. 2016; 23 (6): 2026- 2034.

[61] Razzaq FA , Asif M , Asghar S , et al. Glimepiride-loaded nanoemulgel; development, in vitro characterization, ex vivo permeation and in vivo antidiabetic evaluation. Cells. 2021; 10 (9): 2404.

[62] Ali FR , Shoaib MH , Ali SA , et al. A nanoemulsion based transdermal delivery of insulin: formulation development, optimization, in-vitro permeation across Strat-M® membrane and its pharmacokinetic/pharmacodynamic evaluation. J Drug Deliv Sci Technol. 2022; 71: 103338.

[63] Mostafa DM , El-Alim SHA , Asfour MH , Al-Okbi SY , Mohamed DA , Awad G . Transdermal nanoemulsions of Foeniculum vulgare mill. Essential oil: preparation,Characterization and evaluation of antidiabetic potential. J Drug Deliv Sci Technol. 2015;29:99–106.

[64] Mishra KK , Kaur CD , Verma S , Sahu AK , Dash DK , Kashyap P , Mishra SP . Transethosomes and Nanoethosomes: Recent Approach on Transdermal Drug Delivery System. IntechOpen.. https://doi.org/10.5772/intechopen.81152.

[65] Mishra KK , Kaur CD . Development of BBN-hcl loaded transethosomes for enhanced transdermal delivery. Thai J Pharm Sci. 2022; 46 (2): 191- 202.

[66] Opatha SAT , Titapiwatanakun V , Chutoprapat R . Transfersomes: a promising nanoencapsulation technique for transdermal drug delivery. Pharmaceutics. 2020; 12 (9): 855.

[67] Chauhan MK , Gulati A . Aggrandized transdermal delivery of glimepiride via transfersomes: formulation, evaluation and statistical optimization. J Drug Deliv Ther. 2016; 6 (4): 48- 54.

[68] Ramkanth S , Anitha P , Gayathri R , Mohan S , Babu D . Formulation and design optimization of nano-transferosomes using pioglitazone and eprosartan mesylate for concomitant therapy against diabetes and hypertension. Eur J Pharm Sci. 2021; 162: 105811.

[69] Malakar J , Sen SO , Nayak AK , Sen KK . Formulation, optimization and evaluation of transferosomal gel for transdermal insulin delivery. Saudi Pharm J. 2012; 20 (4): 355- 363.

[70] Abdallah MH , Abu Lila AS , Shawky SM , et al. Experimental design and optimization of nano-transfersomal gel to enhance the hypoglycaemic activity of silymarin. Polymers. 2022; 14 (3): 508.

[71] Thirunavukkarasu A , Nithya R , Jeyanthi J . Transdermal drug delivery systems for the effective management of type 2 diabetes mellitus. Diabetes Res Clin Pract. 2022; 194: 109996.

[72] Islam MR , Uddin S , Chowdhury MR , Wakabayashi R , Moniruzzaman M , Goto M . Insulin transdermal delivery system for diabetes treatment using a biocompatible ionic liquid-based microemulsion. ACS Appl Mater Interfaces. 2021; 13 (36): 42461- 42472.

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