Author(s): Chakraborty. T, Gupta. S, Saini. V


DOI: 10.5958/0974-360X.2020.00727.1   

Address: Chakraborty. T1, Gupta. S1*, Saini. V2
1Department of Pharmaceutical Science, M M College of Pharmacy, , Maharishi Markandeshwar University (Deemed to be University), Mullana, Ambala, Haryana 133207, India.
2Department of Pharmaceutical and Medical Sciences, Maharishi Markandeshwar University, Solan, Laddo, Himachal Pradesh 173229, India.
*Corresponding Author

Published In:   Volume - 13,      Issue - 9,     Year - 2020

Insulin is useful for the treatment of diabetes mellitus. Because of its high molecular weight, it is difficult to permeate through transdermal routes. There is no existing formulation available for the dermatologic manifestation of diabetes. Thus an attempt was made to prepare insulin-loaded microemulsion topical gel with aloe vera. The insulin-loaded microemulsion was prepared using 3 square factorial design, using oleic acid as oil phase, tween-80 as the surfactant and poly ethylene glycol-400 as co-surfactant. Physical stability studies performed and amongst all of them, the best three formulations selected for ex vivo insulin permeation study. The batch with the best permeation was selected to prepare the topical gel with and without aloe vera. Post evaluation parameters of topical gel with skin irritation study and in vivo study performed. In vivo study results revealed that the groups of diabetes Wistar albino rats with skin infections; by the treatment of topical gel of insulin-loaded microemulsion with aloe vera gel was found to reduce the blood glucose level and skin infection as compared to one without aloe vera gel. It was concluded that insulin loaded microemulsion topical gel with aloe vera can be used as dermatologic manifestation of diabetes significantly.

Cite this article:
Chakraborty. T, Gupta. S, Saini. V. In vivo Study of Insulin-loaded Microemulsion Topical gel with Aloe vera for the Treatment of Dermatologic Manifestation of Diabetes. Research J. Pharm. and Tech 2020; 13(9):4115-4124. doi: 10.5958/0974-360X.2020.00727.1

Chakraborty. T, Gupta. S, Saini. V. In vivo Study of Insulin-loaded Microemulsion Topical gel with Aloe vera for the Treatment of Dermatologic Manifestation of Diabetes. Research J. Pharm. and Tech 2020; 13(9):4115-4124. doi: 10.5958/0974-360X.2020.00727.1   Available on:

1.    Brugler A, Thompson S, Turner S, Ngo B, and Rendell M. Skin blood flow abnormalities in diabetic dermopathy. J. Am. Acad. Dermatol. 2011: 65(3); 559–563.
2.    Abdollahi A, Daneshpazhooh M, Amirchaghmaghi E, Sheikhi S, Eshrati B, and Bastanhagh MH. Dermopathy and retinopathy in diabetes: Is there an association? Dermatology .2007: 214(2); 133–136.
3.    Mahmood T and Bari AU. Cutaneous Manifestations of Diabetes Mellitus. Antimicrob. Agents Chemother. 2014; 58(12): 7250–7.
4.    Morgan AJ and Schwartz RA. Diabetic dermopathy: A subtle sign with grave implications. J. Am. Acad. Dermatol. 2008: 58(3); 447–451.
5.    Emre S, Cakır B, Arman A, Demirseren DD, Metin A, Arpacı D, et al. Relationship Between Skin Diseases and Extracutaneous Complications of Diabetes Mellitus: Clinical Analysis of 750 Patients. Am. J. Clin. Dermatol. 2013: 15(1); 65–70.
6.    Bustan RS, Wasim D, Yderstræde KB, and Bygum A. Specific skin signs as a cutaneous marker of diabetes mellitus and the prediabetic state - A systematic review. Dan. Med. J. 2017: 64(1); 1–9.
7.    McCash S and Emanuel PO. Defining diabetic dermopathy. J. Dermatol. 2011: 38(10); 988–992.
8.    Finucane KA and Archer CB. Recent advances in diabetology: Diabetic dermopathy, autoantibodies in the prediction of the development of type 1 diabetes, and islet cell transplantation and inhaled insulin as treatment for diabetes. Clin. Exp. Dermatol. 2006: 31(6); 837–840.
9.    Jain S, Agrawal AK, Rai VK, Yadav NP, and Mishra N. Novel drug delivery system: an immense hope for diabetics. Drug Deliv. 2014: 23(5); 7544: 1–20.
10.    Copenhaver M and Hoffman RP. Type 1 diabetes: where are we in 2017? Transl. Pediatr. 2017; 6(4): 359–364.
11.    Rotella CM, Pala L, and Mannucci E. Role of insulin in the type 2 diabetes therapy: Past, present and Future. Int. J. Endocrinol. Metab. 2013: 11(3); 137–144.
12.    Siddiqui AA, Siddiqui SA, Ahmad S, Siddiqui S, Ahsan I, and Sahu K. Diabetes: Mechanism, pathophysiology and management-A review. Int. J. Drug Dev. Res. 2013: 5(2); 1–23.
13.    Prasad A, Thomas AA, and Mahadevan DSA. To Study The Efficacy of Topical Insulin Vs Conventional Dressing on Wound Healing In Diabetic Foot Ulcers. 2018: 17(4); 33–38.
14.    Tambuwala MM, El-Tanani M, Abdelkader DH, Faheem AM, Mitchell CA, McCarron PA, et al. Enhanced cutaneous wound healing in rats following topical delivery of insulin-loaded nanoparticles embedded in poly(vinyl alcohol)-borate hydrogels. Drug Deliv. Transl. Res. 2018: 8(5); 1053–1065.
15.    Negrini J, Mozos E, Escamilla A, Pérez J, Lucena R, Guerra R, et al. Effects of topical insulin on second-intention wound healing in the red-eared slider turtle (Trachemys scripta elegans) - a controlled study. BMC Vet. Res. 2017: 13(1); 1–10.
16.    Lipsky BA and Hoey C. Topical Antimicrobial Therapy for Treating Chronic Wounds. Clin. Infect. Dis. 2009; 49(10): 1541–1549.
17.    Chang R-K, Raw A, Lionberger R, and Yu L. Erratum to: Generic Development of Topical Dermatologic Products: Formulation Development, Process Development, and Testing of Topical Dermatologic Products. AAPS J. 2015: 17(6); 1522–1522.
18.    Hong Y, Wu Y, Lin Q, Lin L, Zhu X, and Zhang X.  Preparation and evaluation of dl -praeruptorin A microemulsion based hydrogel for dermal delivery . Drug Deliv. 2014; 22(6): 757–764.
19.    Negi P, Singh B, Sharma G, Beg S, Raza K, and Katare OP. Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation. Drug Deliv. 2016: 23(3); 951–967.
20.    Pillai AB, Nair J V., Gupta NK, and Gupta S. Microemulsion-loaded hydrogel formulation of butenafine hydrochloride for improved topical delivery. Arch. Dermatol. Res. 2015; 307(7): 625–633.
21.    Kogan A and Garti N. Microemulsions as transdermal drug delivery vehicles. Adv. Colloid Interface Sci. 2006: 123–126 (16); 369–385.
22.    Nastiti CMRR, Ponto T, Abd E, Grice JE, Benson HAE, and Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics. 2017: 9(4); 1–25.
23.    Guo X and Mei N. Aloe vera: A review of toxicity and adverse clinical effects. J. Environ. Sci. Heal. - Part C Environ. Carcinog. Ecotoxicol. Rev. 2016: 34(2); 77–96.
24.    Andersen FA. Final report on the safety assessment of aloe andongensis extract, aloe andongensis leaf juice, aloe arborescens leaf extract, aloe arborescens leaf juice, aloe arborescens leaf protoplasts, aloe barbadensis flower extract, aloe barbadensis leaf, aloe bar. Int. J. Toxicol. 2007: 26(2); 1–50.
25.    Habeeb F, Shakir E, Bradbury F, Cameron P, Taravati MR, Drummond AJ, et al. Screening methods used to determine the anti-microbial properties of Aloe vera inner gel. Methods. 2007: 42(4); 315–320.
26.    Stabenau J, Ko F, Broemeling LD, Ph D, Robson MC, Winters WD, et al. Beneficial Effect of Aloe on Wound Healing in an Excisional Wound Model. J Altern Complement Med. 1996: 2(2);271–277.
27.    Chithra P, Sajithlal GB, and Chandrakasan G. Influence of Aloe 6 era on the glycosaminoglycans in the matrix of healing dermal wounds in rats. Journal of Ethnopharmacology. 1998: 59(3); 179–186.
28.    Talmadge J, Chavez J, Jacobs L, Munger C, Chinnah T, Chow JT, et al. Fractionation of Aloe vera L . inner gel , purification and molecular profiling of activity. Int Immunopharmacol. 2004: 4(14); 1757–1773.
29.    Reynolds T and Dweck AC. Aloe vera leaf gel : a review update. J Ethnopharmacol. 1999: 68(1-3); 3–37.
30.    Hamman JH. Composition and Applications of Aloe vera Leaf Gel. Molecules. 2008: 13(8);1599–1616.
31.    Surjushe A, Vasani R, and Saple D. Aloe vera: A short review. Indian J. Dermatol. 2008: 53(4); 163–166.
32.    Wheeler BJ and Taylor BJ. Successful management of allergy to the insulin excipient metacresol in a child with type 1 diabetes: A case report. J. Med. Case Rep. 2012: 6(1); 1–4.
33.    Weber C, Kammerer D, Streit B, and Licht AH. Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release. Toxicol. Reports. 2015: 6(2); 194–202.
34.    Rajpar SF, Foulds IS, Abdullah A, and Maheshwari M. Severe adverse cutaneous reaction to insulin due to cresol sensitivity. Contact Dermatitis. 2006: 55(2); 119–120.
35.    Abdul Wadood Khan, Sabna Kotta, Shahid Hussain Ansari, Rakesh Kumar Sharma, Amit Kumar JA. Formulation development, optimization and evaluation of aloe vera gel for wound healing. Eur. J. Pharm. Biopharm. 2013; 9(36): 6–10.
36.    Malakar J, Sen SO, Nayak AK, and Sen KK. Development and Evaluation of Microemulsions for Transdermal Delivery of Insulin. ISRN Pharm. 2011: 2011(7); 1–7.
37.    Pal T, Rajan Ds, Gowda Kv, Mandal U, Ganesan M, Bose A and Sarkar A. Development of RP-HPLC for analysis of human insulin. Indian J. Pharm. Sci. 2006: 68(5); 662-665.
38.    Pavlovic M, Malesevic M, Nikolic K, and Agbaba D. Development and Validation of Hplc Method for Determination of Human Insulin in Pharmaceutical Preparation. J. AOAC Int. 2010: 94(3); 713–722.
39.    Hamishehkar H, Khoshbakht M, Jouyban A, and Ghanbarzadeh S. The relationship between solubility and transdermal absorption of tadalafil. Adv. Pharm. Bull. 2015: 5(3); 411–417.
40.    Stout EI and McKessor A. Glycerin-Based Hydrogel for Infection Control. Adv. Wound Care. 2012: 1(1); 48–51.
41.    Amenabar I, Poly S, Nuansing W, Hubrich EH, Govyadinov AA, Huth F, et al. Structural analysis and mapping of individual protein complexes by infrared nanospectroscopy. Nat. Commun. 2013: 4(2890); 1–9.
42.    Prusty AK and Sahu SK. Development and Evaluation of Insulin Incorporated Nanoparticles for Oral Administration. ISRN Nanotechnol. 2013: 6; 1–6.
43.    Manoharan C and Singh J. Addition of zinc improves the physical stability of insulin in the primary emulsification step of the poly(lactide-co-glycolide) microsphere preparation process. Polymers (Basel). 2015: 7(5); 836–850.
44.    Vij NN and Saudagar RB. Formulation, development and evaluation of film-forming gel for prolonged dermal delivery of terbinafine hydrochloride. Int. J. Pharma Sci. Res. 2014: 5(9); 537–554.
45.    Rowe RC, Sheskey PJ and Quinn ME. Handbook of Pharmaceutical Excipients. Pharmaceutical Press and American Pharmacists Association, USA. 2009: pp. 110, 262, 298, 466, 517, 549.
46.    Pool H, Quintanar D, Figueroa JDD, Marinho Mano C, Bechara JEH, Godínez LA, et al. Antioxidant effects of quercetin and catechin encapsulated into PLGA nanoparticles. J. Nanomater. 2012: 7;1-12.
47.    Piérard GE, Seité S, Hermanns-Lê T, Delvenne P, Scheen A, and Piérard-Franchimont C. The skin landscape in diabetes mellitus. Focus on dermocosmetic management. Clin. Cosmet. Investig. Dermatol. 2013:15(6); 127–135.
48.    Narbutt J, Bednarski IA, and Lesiak A. The effect of an emollient with benfothiamine   and Biolin prebiotic on the improvement of epidermal skin function. Postep. Dermatologii i Alergol. 2016: 33(3); 224–231.

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