更昔洛韦原位凝胶眼给药系统的体内和体外研究。

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Susanta Paul, Subhabrota Majumdar, Mainak Chakraborty, Swarupananda Mukherjee, Nilanjan Sarkar, Bhupendra Prajapati, Nemat Ali, Abdullah F AlAsmari, Shamama Nishat
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引用次数: 0

摘要

由于眼睛独特的解剖和生理结构限制了药物的吸收和分布,眼部给药具有挑战性。滴眼液等传统方法的生物利用度很差,通常需要频繁给药。原位凝胶系统是一种液体配方,在与生理条件(pH值、温度或泪液中的离子)接触后转化为凝胶,为眼部药物输送提供了几个优势。将更昔洛韦掺入热反应原位凝胶基中。采用3²全因子设计,采用冷法制备了9个配方。考察了更昔洛韦凝胶的物理性质,包括清晰度、pH值、粘度、凝胶温度和凝胶时间。采用透析膜法评估体外药物释放,并在家兔模型中评估眼毒性。用波洛沙姆407和HPMC E-50 LV制备凝胶,采用3²因子设计分析不同浓度对凝胶粘度、凝胶温度和凝胶时间的影响。优化后的原位凝胶配方(Batch B5)含有15% w/v的poloxam407和1% w/v的HPMC E-50 LV,凝胶粘度为64.81 cPs,凝胶温度为39.0℃,凝胶时间为183 s。该制剂比商业制剂具有更好的渗透性和更昔洛韦的持续释放。眼毒性研究证实该制剂无刺激性且耐受性良好。总体而言,该凝胶具有良好的物理性能,持续释放时间超过12 h,具有显著的提高药物生物利用度和治疗眼部感染疗效的潜力。这些结果证实,优化后的更昔洛韦原位凝胶制剂提高了眼透性,延长了眼滞留时间,从而提高了其治疗效果。它的持续释放和延长的滞留时间使其成为传统滴眼液的有希望的替代品,提供更好的患者依从性和疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In-situ gel bases ocular delivery system of Ganciclovir, in-vivo and in-vitro investigation.

Ocular drug delivery is challenging due to the eye's unique anatomy and physiology, which limit drug absorption and distribution. Traditional methods like eye drops have poor bioavailability and often require frequent dosing. In-situ gel systems, liquid formulations that transform into a gel upon contact with physiological conditions (pH, temperature, or ions in tear fluid), offer several advantages for ocular drug delivery. Ganciclovir was incorporated into a thermoresponsive in situ gel base. Nine formulations were prepared using the cold technique and a 3² full factorial design. The physical properties of ganciclovir gel, including clarity, pH, viscosity, gelation temperature, and gelation time, were scrutinized. In vitro drug release was assessed using a dialysis membrane method, and ocular toxicity was evaluated in a rabbit model. Poloxamer 407 and HPMC E-50 LV were used to prepare the gel, with the 3² factorial design analyzing the effects of varying concentrations on the gel's viscosity, gelation temperature, and gelation time. The optimized in-situ gel formulation (Batch B5) contained 15% w/v poloxamer 407 and 1% w/v HPMC E-50 LV, achieving a viscosity of 64.81 cPs, with a gelation temperature of 39.0 °C and a gelation time of 183 s. This formulation demonstrated better permeability and sustained ganciclovir release than a commercial formulation. Ocular toxicity studies confirmed that the formulation was non-irritating and well-tolerated. Overall, the gel showed suitable physical properties, sustained drug release over 12 h, and significant potential for enhancing drug bioavailability and treatment efficacy for ocular infections. These findings confirm that the optimized ganciclovir in situ gel preparation improves eye permeation and prolongs ocular retention time, thus enhancing its therapeutic efficacy. Its sustained release and prolonged retention time make it a promising alternative to conventional eye drops, offering better patient compliance and efficacy.

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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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