Rahbar Nadereh, Darvish Sarah, Farrahi Fereydoun, Kouchak Maryam
Nanotechnology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Drug Deliv Transl Res. 2025 Apr;15(4):1210-1220. doi: 10.1007/s13346-024-01663-1. Epub 2024 Jul 8.
Due to the small capacity of the eye cavity and the rapid drainage of liquid into the nasolacrimal duct, patients must frequently administer the drops. Nanoparticles (NPs) and in situ gel systems have each proven their ability to achieve eye retention independently. In this study, timolol-loaded chitosan-carbomer NPs were prepared using the polyelectrolyte complexation method, and incorporated into a pH-responsive in situ gel system made of carbomer. The rheological behavior of NPs-laden in situ gel was examined at room and physiological conditions. Characteristics such as zeta potential, surface tension, refractive index, mucoadhesive properties, drug release, transcorneal permeability, and intra-ocular pressure (IOP) lowering activity were investigated on NPS and NPs-laden in situ gel formulations. The optimum gained NPs system had an encapsulation efficiency of about 69% with a particle size of 196 nm. The zeta potential of the NP and NPs-laden in situ gel were - 16 and + 11 mV respectively. NPs-laden in situ gel presented enhanced viscosity at physiological pH. All physicochemical properties were acceptable for both formulations. NPs and NPs-laden in situ gel systems proved to sustain drug release. They showed mucoadhesive properties which were greater for NPs-laden in situ gel. IOP reduction by NPs-laden in situ gel was significantly higher and more long-lasting than the timolol solution and NPs. In conclusion, the developed NPs-laden in situ gel is a promising carrier for ocular drug delivery due to the slow release of drug from nanoparticles, its mucoadhesive properties, and high viscosity acquisition in contact with precorneal film, which lead to improved therapeutic efficacy.
由于眼腔容量小且液体迅速排入鼻泪管，患者必须频繁滴眼。纳米颗粒（NPs）和原位凝胶系统已各自证明了其独立实现眼内滞留的能力。在本研究中，采用聚电解质络合法制备了载有噻吗洛尔的壳聚糖 - 卡波姆纳米颗粒，并将其纳入由卡波姆制成的pH响应原位凝胶系统中。在室温和生理条件下研究了载有纳米颗粒的原位凝胶的流变行为。对纳米颗粒和载有纳米颗粒的原位凝胶制剂研究了诸如zeta电位、表面张力、折射率、粘膜粘附特性、药物释放、角膜透过性和降低眼内压（IOP）活性等特性。所获得的最佳纳米颗粒系统的包封率约为69%，粒径为196nm。纳米颗粒和载有纳米颗粒的原位凝胶的zeta电位分别为 - 16和 + 11mV。载有纳米颗粒的原位凝胶在生理pH下表现出增强的粘度。两种制剂的所有物理化学性质均可接受。纳米颗粒和载有纳米颗粒的原位凝胶系统被证明能够持续释放药物。它们表现出粘膜粘附特性，载有纳米颗粒的原位凝胶的粘膜粘附特性更强。载有纳米颗粒的原位凝胶降低眼内压的效果明显高于噻吗洛尔溶液和纳米颗粒，且更持久。总之，所开发的载有纳米颗粒的原位凝胶是一种有前途的眼部药物递送载体，因为药物从纳米颗粒中缓慢释放，其具有粘膜粘附特性，并且与角膜前膜接触时获得高粘度，从而提高了治疗效果。
