The present research work was designed to develop dorzolamide-loaded chitosan-coated polycaprolactone nanoparticles (DRZ-CS-PCL-NPs) for improved ocular delivery. The nanoparticles were prepared by single-step emulsification technique and optimized using the three-factor three-level Box-Behnken design. The optimized DRZ-CS-PCL-NPs prepared with the composition of polycaprolactone (60 mg), chitosan (0.6%) and polyvinyl alcohol (1.5%). The particle size, polydispersity index, zeta potential and encapsulation efficiency of optimized DRZ-CS-PCL-NPs were found to be 192.38 ± 6.42 nm, 0.18 ± 0.04, +5.21 ± 1.24 mV, and 72.48 ± 5.62%, respectively. The dependent and independent response variables showed excellent correlation and signifying the rationality of the optimized DRZ-CS-PCL-NPs. The DRZ release from CS-PCL-NPs showed biphasic behaviour with initial burst release for 2 h after that sustained-release up to 12 h of study. The corneal flux experiment showed many fold enhancement in permeation across goat cornea. DRZ-CS-PCL-NPs exhibited 3.7 fold higher mucoadhesive strength compared to the control. Furthermore, the histopathological assessment and HET-CAM study revealed that the DRZ-CS-PCL-NPs were non-irritant and safe for ocular administration. Therefore, from the present study, it can be concluded that the optimized DRZ-CS-PCL-NPs are safe and have the potential for successful ocular delivery and improved therapeutic efficacy.

本研究工作旨在开发负载多佐胺的壳聚糖涂层聚己内酯纳米颗粒（DRZ-CS-PCL-NPs），以改善眼部输送。通过单步乳化技术制备纳米颗粒，并使用三因素三级Box-Behnken设计对其进行优化。以聚己内酯（60 mg），壳聚糖（0.6％）和聚乙烯醇（1.5％）的组成制备的优化DRZ-CS-PCL-NP。优化的DRZ-CS-PCL-NP的粒径，多分散指数，ζ电位和包封效率分别为192.38±6.42 nm，0.18±0.04，+ 5.21±1.24 mV和72.48±5.62％。相关和独立响应变量显示出极好的相关性，并表明优化的DRZ-CS-PCL-NP的合理性。从CS-PCL-NPs释放的DRZ表现出双相行为，在持续释放长达12h的研究后2h首次爆发释放。角膜通量实验显示，跨山羊角膜的渗透性提高了许多倍。与对照相比，DRZ-CS-PCL-NPs的粘膜粘附强度高3.7倍。此外，组织病理学评估和HET-CAM研究表明，DRZ-CS-PCL-NP对眼部给药无刺激性和安全性。因此，从本研究中可以得出结论，优化的DRZ-CS-PCL-NP是安全的，并且具有成功进行眼部递送和改善治疗效果的潜力。与对照相比，粘膜黏附强度高7倍。此外，组织病理学评估和HET-CAM研究表明，DRZ-CS-PCL-NP对眼部给药无刺激性和安全性。因此，从本研究中可以得出结论，优化的DRZ-CS-PCL-NP是安全的，并且具有成功进行眼部递送和改善治疗效果的潜力。与对照相比，粘膜黏附强度高7倍。此外，组织病理学评估和HET-CAM研究表明，DRZ-CS-PCL-NP对眼部给药无刺激性和安全性。因此，从本研究中可以得出结论，优化的DRZ-CS-PCL-NP是安全的，并且具有成功进行眼部递送和改善治疗效果的潜力。