(T1230-01-04) Iontophoretic Transdermal Delivery of a Bioactive Molecule: Comparison of Nanoliposomal Platforms with Passive Delivery

Purpose: Asenapine maleate (ASP) is an antipsychotic agent clinically utilized for the treatment of schizophrena and bipolar disorder. Due to extensive metabolism in the liver, its oral bioavailability is < 2%, necessitating alternative routes of administration. The objective of this work was to investigate transdermal route of delivery of ASP using iontophoresis, with both nanoparticulate carriers (nanoliposomes) and plain drug in solution form.

Methods: ASP nanoliposomes were prepared by thin film hydration, followed by size reduction using ultrasonication. Particle size (and size distribution), surface charge (zeta potential) and drug entrapment efficiency were identified and optimized as the output variables. Optimized liposomes were conjugated with a novel in-house synthesized peptide. Ex vivo permeation studies of the developed formulation along with application of iontophoresis was compared with passive delivery and with iontophoresis using plain drug alone, on male Sprague Dawley rat skin for 6 h (n=3).

Results: The amount of drug permeated in 6 h (Q₆) with pH 7.4 phosphate buffer was found to be 22.48±2.6 µg/cm² and 25.27±3.45 µg/cm², with passive diffusion and iontophoresis, respectively, with the difference not being statistically significant. The developed formulation (positively charged) subjected to anodic iontophoresis displayed significantly (p < 0.05) higher permeation of ASP compared to both passive diffusion of ASP and to iontophoretic permeation of plain ASP in buffer. The highest values of Q₆, flux (J_ss) and enhancement ratio (ER) were observed with (anodic) iontophoresis of one batch of optimized formulation (Q₆: 783.41±25.03 µg/cm²; J_ss: 138.57±18.16 µg/cm²/h, 38.66±5.07).

Conclusion: The iontophoretic transdermal delivery of nanoliposome-based formulation of ASP was investigated in vitro and ex vivo and was found to be a promising drug delivery strategy in the treatment of schizophrenia and bipolar disorder.

References: 1. Manikkath J, Parekh HS, Mutalik S. Surface-engineered nanoliposomes with lipidated and non-lipidated peptide-dendrimeric scaffold for efficient transdermal delivery of a therapeutic agent: Development, characterization, toxicological and preclinical performance analyses. Eur J Pharm Biopharm. 2020, 156:97-113
2. Zoghi A, Khosravi-Darani K, Omri A. Process Variables and Design of Experiments in Liposome and Nanoliposome Research. Mini-Reviews Med. 2018, Chem. 18(4):324-344