Gaikwad Mahesh, George Amal, Sivadas Aparna, Karunakaran Kavitha, N Sudheesh, Byradeddy Siddappa N, Mukhopadhyay Chiranjay, Mudgal Piya Paul, Kulkarni Madhur
SCES's Indira College of Pharmacy, New Mumbai Pune Highway, Tathawade, Pune, India.
Manipal Institute of Virology, Manipal Academy of Higher Education, Manipal, India.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar;398(3):3103-3117. doi: 10.1007/s00210-024-03468-y. Epub 2024 Sep 30.
Herpes simplex virus type 2 (HSV-2) treatment faces challenges due to antiviral resistance and systemic side effects of oral therapies. Local delivery of antiviral agents, such as tenofovir (TDF) and zinc acetate dihydrate (ZAD), may offer improved efficacy and reduced systemic toxicity. This study's objective is to develop and evaluate local unit dose formulations of TDF and ZAD combination for local treatment of HSV-2 infection and exploring their individual and combinatory effects in vitro. The study involved the development of immediate-release film and pessary formulations containing TDF and ZAD. These formulations were characterized for physicochemical properties and in vitro drug release profiles. Cytotoxicity and antiviral activity assays were conducted to evaluate the individual and combinatory effects of TDF and ZAD. Film formulations released over 90% of the drugs within 1 h, and pessary formulations within 90 min, ensuring effective local drug delivery. ZAD showed moderate antiviral activity while TDF exhibited significant antiviral activity at non-cytotoxic concentrations. The combination of TDF and ZAD demonstrated synergistic effects in co-infection treatments, reducing the concentration required for 50% inhibition of HSV-2. Developed film and pessary formulations offer consistent and predictable local drug delivery, enhancing antiviral efficacy while minimizing systemic side effects. The combination of TDF and ZAD showed potential synergy against HSV-2, particularly in co-infection treatments. Further preclinical studies on pharmacokinetics, safety, and efficacy are necessary to advance these formulations toward clinical application.
由于抗病毒耐药性和口服疗法的全身副作用，单纯疱疹病毒2型（HSV-2）的治疗面临挑战。局部递送抗病毒药物，如替诺福韦（TDF）和二水合醋酸锌（ZAD），可能会提高疗效并降低全身毒性。本研究的目的是开发和评估TDF和ZAD组合的局部单位剂量制剂，用于局部治疗HSV-2感染，并在体外探索它们的单独和联合作用。该研究涉及开发含有TDF和ZAD的速释薄膜和阴道栓剂制剂。对这些制剂的理化性质和体外药物释放曲线进行了表征。进行了细胞毒性和抗病毒活性测定，以评估TDF和ZAD的单独和联合作用。薄膜制剂在1小时内释放了超过90%的药物，阴道栓剂制剂在90分钟内释放，确保了有效的局部药物递送。ZAD显示出中等抗病毒活性，而TDF在非细胞毒性浓度下表现出显著的抗病毒活性。TDF和ZAD的组合在共感染治疗中显示出协同作用，降低了抑制HSV-2 50%所需的浓度。开发的薄膜和阴道栓剂制剂提供了一致且可预测的局部药物递送，提高了抗病毒疗效，同时将全身副作用降至最低。TDF和ZAD的组合对HSV-2显示出潜在的协同作用，特别是在共感染治疗中。有必要对这些制剂进行进一步的药代动力学、安全性和疗效的临床前研究，以推动其临床应用。
