Enhanced glycemic control and organ protection with empagliflozin microemulsion in alloxan-induced diabetic mice
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20261957Keywords:
Diabetes mellitus, Alloxan, Hypoglycemic activity, Empagliflozin, MicroemulsionAbstract
Background: Diabetes mellitus (DM) is a serious challenge for worldwide health and is predominant in most populations living with type 2 diabetes (T2DM), thus new drug strategies must be created to enhance drug delivery and use. Empagliflozin is also a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has high solubility and low intestinal permeability, thereby making its bioavailability in traditional formulations is limited. To overcome these drawbacks, we have formulated an empagliflozin microemulsion, which we expect to enhance permeability and therapeutic efficacy.
Methods: The microemulsion was formulated according to a double emulsion technique with olive oil, Tween 80, ethanol, and xanthan gum, and followed by analysis on physical properties, stability, and drug release kinetics. The microemulsion was compared to the empagliflozin tablet for glycemic control and protection of organs in alloxan-induced diabetic Swiss albino mice.
Results: The formulation yielded spherical droplets (0.2-0.3 µm), high encapsulation efficiency (EE) (84.9%), and sustained in vitro release (76% after 12 h). The in vivo findings indicated the microemulsion was more effective, with 63.50% reduction in blood glucose levels vs. 55.70% for the tablet, and a significant recovery of body weight (30.16 g vs. 28.93 g). Histopathological examination of microemulsion group revealed restored pancreatic islets and normal renal structures in contrast to significant destruction in diabetic controls.
Conclusions: These results emphasize the ability of the microemulsion to enhance the pharmacodynamic profile of empagliflozin and can be considered as a new alternative to classical drugs in diabetes treatment. This study highlights significance of the above therapeutic benefits including patient compliance in a novel phase of drug delivery systems.
References
Rama Rao T, Tejomurtula GN. Diabetes Mellitus: A Review. Int. J. Med. Sci. Pharma Res. 2024;10(2):5-9.
Shah N, Abdalla MA, Deshmukh H, Sathyapalan T. Therapeutics for type-2 diabetes mellitus: a glance at the recentinclusions and novel agents under development for use in clinicalpractice. Ther Adv Endocrinol Metab. 2021;12(1):204201882110421.
Forycka J, Hajdys J, Krzemińska J, Wilczopolski P, Wronka M, Młynarska E, et al. New Insights into the Use of Empagliflozin-A Comprehensive Review. Biomedicines. 2022;10(12):3294.
Yadav J, Ahsan F, Panda P, Mahmood T, Ansari VA, Shamim A. Empagliflozin-A Sodium Glucose Co-transporter-2 Inhibitor: Overview of its Chemistry, Pharmacology, and Toxicology. Curr Diabetes Rev. 2024;20(10):e230124226010.
Niguram P, Polaka SN, Rathod R, Kalia K, Kate AS. Update on compatibility assessment of empagliflozin with the selected pharmaceutical excipients employed in solid dosage forms by thermal, spectroscopic and chromatographic techniques. Drug Dev Ind Pharm. 2020;46(2):209-18.
He CX, He ZG, Gao JQ. Microemulsions as drug delivery systems to improve the solubility and the bioavailability of poorly water-soluble drugs. Expert Opin. Drug Deliv. 2010;7(4):445-60.
Abdelrahim ME, Abdelbary A, Ghorab M. Formulation and evaluation of medicated microemulsion for topical application. Int J Clin Med Res. 2024;2(3):73-7.
Areses-Huete T, Cordoba-Diaz D, Torres-Suárez AI, Cordoba-Diaz M. Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration. Pharmaceutics. 2024;16(6):705.
Yang J, Xu H, Wu S, Ju B, Zhu D, Yan Y, et al. Preparation and evaluation of microemulsion based transdermal delivery of Cistanche tubulosa phenylethanoid glycosides. Mol Med Rep. 2017;15(3):1109-16.
Masmoudi H, Piccerelle P, Le Dréau Y, Kister J. A Rheological Method to Evaluate the Physical Stability of Highly Viscous Pharmaceutical Oil-in-Water Emulsions. Pharm Res. 2006;23(8):1937-47.
Abbot M, Yin F, Piskunov M, Roisman IV, Hussong J. Elucidating on the drop impact dynamics of water-in-oil microemulsions via advanced rheometry. Colloids Surf. A: Physicochem. Eng Asp. 2025;720:136952.
Li L, Qu J, Liu W, Peng B, Cong S, Yu H, et al. Advancements in Characterization Techniques for Microemulsions: From Molecular Insights to Macroscopic Phenomena. Molecules. 2024;29(12):2901.
Kumar PM; Ghosh A. Development and evaluation of silver sulphadiazine loaded microsponge based gel for partial thickness (Second degree) burn wounds. Eur J Pharm Sci. 2017;96:243-54.
Gómez-Lázaro L, Martín-Sabroso C, Aparicio-Blanco J, Torres-Suárez AI. Assessment of In Vitro Release Testing Methods for Colloidal Drug Carriers: The Lack of Standardized Protocols. Pharmaceutics. 2024;16(1):103.
Bhonge A, Bakade BV. Design, Development and Evaluation of Microemulsion for Topical Drug Delivery System Using Model Drug. J Drug Des Res. 2024;11(1):1097.
Oshkondali STM, Mahmoudy E, Samira F, Alacrouk A, Abu KM, Rashed A, et al. Alloxan Dose Optimization to Induce Diabetes in Albino Mice and the Determination of the Induced Diabetes Type. Saudi J Med Pharm Sci. 2019;05(10):913-16.
Olenovych O, Boychuk T, Davydenko I, Davydenko O. Histomorphological peculiarities of the pancreatic parenchyma in rats with alloxan-induced diabetes of different duration. Neonatol Surg Perinat Med. 2024;142(52):100-7.
Hassan SF, Asghar S, Ullah Khan I, Munir R, Khalid SH. Curcumin Encapsulation in Geranium Oil Microemulsion Elevates Its Antibacterial, Antioxidant, Anti-Inflammatory, and Anticancer Activities. ACS Omega. 2024;9(5):5624-36.
Zhang J, Wang Z, Liao M, Li S, Feng Q, Cao X. Curcumin-laden amphiphilic chitosan microemulsion with enhanced transdermal delivery, skin compatibility and anti-arthritic activity. J Drug Deliv Sci Technol. 2022;78:103997.
Hu L, Wu H, Niu F, Yan C, Yang X, Jia Y. Design of fenofibrate microemulsion for improved bioavailability. Int J Pharm. 2011;420(2):251-5.
Patel RB, Patel MR, Bhatt KK, Patel BG, Gaikwad RV. Evaluation of brain targeting efficiency of intranasal microemulsion containing olanzapine: pharmacodynamic and pharmacokinetic consideration. Drug Deliv. 2016;23(1):307-15.
Mehta SK, Kaur G, Bhasin KK. Analysis of Tween based microemulsion in the presence of TB drug rifampicin. Colloids Surf B Biointerfaces. 2007;60(1):95-104.
Hu L, Yang J, Liu W, Li L. Preparation and evaluation of ibuprofen-loaded microemulsion for improvement of oral bioavailability. Drug Deliv. 2011;18(1):90-5.
Rogerio AP, Dora CL, Andrade EL, Chaves JS, Silva LF, Lemos-Senna E, et al. Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice. Pharmacol Res. 2010;61(4):288-97.
Wang Y, Wu KC, Zhao BX, Zhao X, Wang X, Chen S, et al. A novel paclitaxel microemulsion containing a reduced amount of Cremophor EL: pharmacokinetics, biodistribution, and in vivo antitumor efficacy and safety. J Biomed Biotechnol. 2011;2011:854872.
Kang BK, Chon SK, Kim SH, Jeong SY, Kim MS, Cho SH, et al. Controlled release of paclitaxel from microemulsion containing PLGA and evaluation of anti-tumor activity in vitro and in vivo. Int J Pharm. 2004;286(1-2):147-56.
Alkhaldi M, Sengupta S, Keck CM. Curcumin Microemulsions: Influence of Compositions on the Dermal Penetration Efficacy. Pharmaceutics. 2025;17(3):301.
Patel V, Kukadiya H, Mashru R, Surti N, Mandal S. Development of microemulsion for solubility enhancement of clopidogrel. Iran J Pharm Res. 2010;9(4):327-34.
Hong SS, Lee SH, Lee YJ, Chung SJ, Lee MH, Shim CK. Accelerated oral absorption of gliclazide in human subjects from a soft gelatin capsule containing a PEG 400 suspension of gliclazide. J Control Release. 1998;51(2-3):185-92.
Sharma G, Wilson K, van der Walle CF, Sattar N, Petrie JR, Ravi Kumar MN. Microemulsions for oral delivery of insulin: design, development and evaluation in streptozotocin induced diabetic rats. Eur J Pharm Biopharm. 2010;76(2):159-6.
Eid RK, Arafa MF, El Maghraby GM. Water in nigella oil microemulsion for enhanced oral bioavailability of linagliptin. Drug Deliv Transl Res. 2025;15(2):596-608.
Soetikno V, Watanabe K, Sari FR, Harima M, Thandavarayan RA, Veeraveedu PT, et al. Curcumin attenuates diabetic nephropathy by inhibiting PKC-α and PKC-β1 activity in streptozotocin-induced type I diabetic rats. Mol Nutr Food Res. 2011;55(11):1655-65.
Naseeb M, Albajri E, Almasaudi A, Alamri T, Niyazi HA, Aljaouni S, et al. Rutin Promotes Wound Healing by Inhibiting Oxidative Stress and Inflammation in Metformin-Controlled Diabetes in Rats. ACS Omega. 2024;9(30):32394-406.
Hagiya H, Miyawaki K, Yamamoto N, Yoshida H, Kitagawa A, Asaoka T, et al. Ceftriaxone-induced Neurotoxicity in a Patient after Pancreas-Kidney Transplantation. Intern Med. 2017;56(22):3103-7.
Kadowaki D, Anraku M, Tasaki Y, Taguchi K, Shimoishi K, Seo H, et al. Evaluation for antioxidant and renoprotective activity of olmesartan using nephrectomy rats. Biol Pharm Bull. 2009;32(12):2041-5.
Xue S, Li YX, Lu XX, Tang W. Dapagliflozin can alleviate renal fibrosis in rats with streptozotocin induced type 2 diabetes mellitus. Exp Ther Med. 2023;26(6):572.
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