Ionic Liquid-Mediated Transdermal Delivery of Organogel Containing Cyclosporine A for the Effective Treatment of Psoriasis

Deepanjan Datta; Sony Priyanka Bandi; Venkata Vamsi Krishna Venuganti

doi:10.1021/acsomega.4c05346

Ionic Liquid-Mediated Transdermal Delivery of Organogel Containing Cyclosporine A for the Effective Treatment of Psoriasis

ACS Omega. 2024 Sep 25;9(40):41565-41582. doi: 10.1021/acsomega.4c05346. eCollection 2024 Oct 8.

Authors

Deepanjan Datta^{1

2}, Sony Priyanka Bandi^{1

3}, Venkata Vamsi Krishna Venuganti¹

Affiliations

¹ Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad, Telangana State 500078, India.
² Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka State 576104, India.
³ Loka Laboratories Private Limited, Technology Business Incubator, BITS Pilani Hyderabad Campus, Jawahar Nagar, Medchal, Telangana 500078, India.

Abstract

The dermal delivery of peptide therapeutics that are of high molecular weight is a challenge. Cyclosporine A (CsA) is a cyclic undecapeptide with poor aqueous solubility and high molecular weight (1202 Da) indicated for psoriasis. The objective of the study was to evaluate the effect of ionic liquids mixed with the Pluronic F127 matrix in skin permeation of CsA and its efficacy in psoriasis treatment. Choline and geranic acid (CAGE) ionic liquids in a 1:2 molar ratio were mixed with Pluronic F127 (22.7%) and PEG 400 (45%) to prepare an organogel formulation. The CsA-loaded CAGE (CsA-CAGE) and CAGE-Pluronic F127 gels (CsA-CAGE-P gel) were characterized for physical and rheological characteristics. The skin transport studies showed that free CsA did not permeate across the excised porcine skin after 48 h. The amount of CsA permeated across the oleic acid (0.25% v/v) and palmitic acid (0.25% w/v) cotreated skin was found to be 244 ± 4 and 1236 ± 17 μg/cm², respectively. The application of CsA-CAGE and CsA-CAGE-P gel enhanced CsA flux by 110- and 135-fold, respectively, compared with the control. The thermal analysis and biophysical studies changed the barrier property of the skin significantly (p < 0.05) after incubation with CAGE and CAGE-P gel. The pharmacokinetic studies in the rat model showed that topical application of CsA-CAGE-P gel provided 2.6- and 1.9-fold greater C _max and AUC_0-t, respectively, compared to the control group. In vitro-in vivo level A correlations were established with R ² values of 0.991 and 0.992 for both linear and polynomial equations for the CsA-CAGE-P gel formulation using the Wagner-Nelson method. The topical application of CsA-CAGE-P gel (10 mg/kg) on an imiquimod-induced plaque psoriatic model reduced the area of the psoriasis and severity index (PASI) score significantly for erythema and scaling, reversing the changes to skin thickness, blood flow rate, and transepidermal water loss. Together, CAGE-Pluronic F127 organogel was developed as an effective topical formulation for the local and systemic delivery of CsA for the treatment of psoriasis.