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Abstract

Doxycycline hyclate is a broad-spectrum tetracycline- class antibacterial agent. It is available in 75 mg, 100 mg, and 150 mg delayed-release tablets for oral use, and widely prescribed in dermatology for treatment of acne vulgaris. Despite the favorable long-term track record of safety, the prolonged oral therapy usually applied in acne vulgaris is associated with side effects such as gastrointestinal side effects (i.e., esophagitis) and dose-related photosensitivity. To this end, it is essential to develop a topical formulation as an alternative to oral dosage forms. The purpose of this study is to formulate chitosan/hyaluronic acid nanogels for the topical delivery of doxycycline hyclate for the first time. The selected nanogel formula exhibited a hydrodynamic diameter and polydispersity index (PDI) of 196.25±1.65 nm and 0.168±0.016, respectively. In addition, it exhibited a positive surface charge (44±2.2 mV), which indicates adequate physical stability. With respect to ex vivo permeation, limited drug permeation was noticed within the first 12 hours of application onto mouse skin. Findings from antibacterial activity revealed an enhanced antibacterial effectiveness of doxycycline hyclate against S. epidermidis upon encapsulation of doxycycline hyclate into chitosan/hyaluronic acid nanogel. The selected formula exhibited excellent biocompatibility, maintaining cell viability above 90% across all tested concentrations, with no significant concentration-dependent cytotoxicity. Accordingly, doxycycline-loaded chitosan/hyaluronic acid nanogels appear to be promising for topical delivery and a potential alternative to the conventional tablet formulations‎.

Keywords: Doxycycline hyclate, Nanogels, Acne vulgaris, Antibacterial activity, Energy-dispersive X-ray

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