Formulation and Evaluation of Isotretinoin Nano Sponges-Loaded Transdermal Patch: A Review

Isotretinoin, an oral retinoid derived from vitamin A, remains one of the most effective agents available for the management of moderate-to-severe and treatment-resistant acne vulgaris because it simultaneously addresses sebum overproduction, follicular hyper keratinization, Cuti bacterium acnes proliferation, and inflammation. However, its clinical use by the oral route is limited by teratogenicity, mucocutaneous dryness, hyperlipidemia, hepatotoxicity, and musculoskeletal and psychiatric adverse effects, while conventional topical isotretinoin formulations suffer from poor aqueous solubility, photo instability, and marked skin irritation. Nano sponge technology, comprising hyper-cross-linked polymeric or cyclodextrin-based three-dimensional networks capable of entrapping lipophilic and poorly soluble drugs within nanosized cavities, offers a promising platform to improve isotretinoin's solubility, stability, and localized skin delivery while minimizing systemic exposure. Incorporating isotretinoin-loaded nano sponges into a transdermal patch further combines the sustained- and controlled-release advantages of matrix-type transdermal drug delivery systems with the solubilization and targeting benefits of nano sponges. This review compiles and synthesizes the current literature on the pharmacology and limitations of isotretinoin, the design and preparation methods of nano sponges, transdermal patch technology, and the physic ochemical, in vitro, ex vivo, and stability evaluation parameters relevant to the formulation and evaluation of an isotretinoin nano sponge-loaded transdermal patch, and it outlines the advantages, challenges, and future prospects of this delivery approach.