Proniosome Gel for Chikungunya: Integrating Novel Drug Delivery with PBPK Modeling for Enhanced Therapeutic Outcomes

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Introduction: Chikungunya Virus (CHIKV), a mosquito-borne alphavirus, poses a persistent global health challenge due to the lack of effective antiviral therapies or vaccines. The infection manifests with acute fever and chronic arthralgia, often resulting in prolonged disability and economic burden. This study investigates proniosome-based drug delivery systems as a nov-el therapeutic platform to alleviate inflammation and viral progression associated with CHIKV infection. Methods: An extensive literature review and preclinical evaluations were conducted to assess proniosomal formulations. Proniosomes were prepared using surfactants, cholesterol, and stabi-lizers, followed by analysis of physicochemical characteristics, encapsulation efficiency, and drug release profiles. Antiviral efficacy was evaluated using Vero, HeLa, and macrophage cell lines infected with CHIKV, and in vivo assessments were performed in CHIKV-infected murine models. Results: Proniosomal formulations exhibited high encapsulation efficiency, sustained drug re-lease, and potent antiviral activity. Myricetin- and ribavirin-loaded proniosomes markedly inhib-ited CHIKV replication with minimal cytotoxicity in vitro. In vivo studies demonstrated reduced viral load, improved survival rates, attenuated inflammatory markers, and enhanced antiviral an-tibody production. The formulations displayed strong biocompatibility and low systemic toxicity. Discussion: The findings underscore the therapeutic promise of proniosomal carriers in enhanc-ing antiviral drug stability, bioavailability, and targeted delivery. The system’s controlled release and low toxicity profile position it as a viable alternative to conventional delivery methods. However, further pharmacokinetic and clinical studies are essential to confirm its translational relevance. Conclusion: Proniosome-based systems offer an innovative, safe, and cost-effective approach to CHIKV management, potentially guiding future antiviral therapy development.

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