Drug Delivery Research Laboratory, Centre of relevance and Excellence in NDDS, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
Drug Delivery Research Laboratory, Centre of relevance and Excellence in NDDS, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Donor's Plaza, Fatehgunj, Vadodara 390002, India.
Mater Sci Eng C Mater Biol Appl. 2017 Feb 1;71:529-540. doi: 10.1016/j.msec.2016.10.017. Epub 2016 Oct 15.
The present investigation was carried out to demonstrate with the help of in vitro and in vivo studies that nanoparticles impregnated ocular inserts effectively delivers significant concentration of drug to the posterior segment of eye after topical administration for treatment of glaucoma. Drug loaded Nanoparticles and their ocular insert have been reported to reduce side effects of orally administered Acetazolamide. Eudragit NPs were prepared by the solvent diffusion nanoprecipitation technique. The prepared NPs were evaluated for various parameters such as particle size, zeta potential, % entrapment efficiency, % drug loading, DSC, FTIR, TEM and stability studies. Ocular inserts of NPs were prepared by solvent casting method. The prepared ocular inserts were evaluated for thickness, content uniformity, folding endurance, disintegration time, morphology and stability study. The NPs and ocular inserts were evaluated for in-vitro drug diffusion study, ex-vivo trans-corneal permeability study, in-vivo ocular tolerability and intra ocular pressure (IOP) reduction study. The optimized batch was stable for a period of 3months in lyophilized form. The optimized formulations had size range of 367nm±8nm, zeta potential around +7mV±1.3mV and 51.61%±3.84% entrapment efficiency with 19%±1.40% drug loading. The ex-vivo trans-corneal study showed higher cumulative corneal permeation, flux across corneal tissue (2.460±0.028μg/ml) and apparent corneal permeability (3.926×10cm/s & 3.863×10cm/s) from drug loaded Eudragit NPs and Ocular inserts as compared to drug solution (0.671±0.020μg/ml & 3.166×10cm/s). In-vivo study showed the Eudragit NPs and ocular insert produced significant (P<0.001) lowering in intra ocular pressure compared with the solution of free drug after 3h of topical ocular administration. Plain Eudragit NPs caused no inflammation and/or discomfort in rabbit eyes and neither affected the intra ocular pressure establishing their safety and non irritancy.
本研究通过体外和体内研究证明，经眼部给药后，载药纳米粒眼用植入剂可有效将药物递送至眼后段，用于治疗青光眼。载药纳米粒及其眼用植入剂已被报道可降低乙酰唑胺口服给药的副作用。采用溶剂扩散沉淀法制备 Eudragit NPs。对所制备的 NPs 进行了各种参数的评价，如粒径、zeta 电位、%包封效率、%载药量、差示扫描量热法（DSC）、傅里叶变换红外光谱（FTIR）、透射电子显微镜（TEM）和稳定性研究。采用溶剂浇铸法制备 NPs 眼用植入剂。对所制备的眼用植入剂进行了厚度、含量均匀度、耐折性、崩解时间、形态和稳定性研究。对 NPs 和眼用植入剂进行了体外药物扩散研究、离体角膜透过性研究、体内眼耐受性和眼内压（IOP）降低研究。优化批在冻干形式下稳定 3 个月。优化的配方粒径范围为 367nm±8nm，zeta 电位约为+7mV±1.3mV，包封效率为 51.61%±3.84%，载药量为 19%±1.40%。离体角膜透过性研究显示，与药物溶液（0.671±0.020μg/ml 和 3.166×10cm/s）相比，载药 Eudragit NPs 和眼用植入剂具有更高的累积角膜透过率、跨角膜组织通量（2.460±0.028μg/ml）和表观角膜透过性（3.926×10cm/s 和 3.863×10cm/s）。体内研究表明，与游离药物溶液相比，Eudragit NPs 和眼用植入剂在眼部给药 3 小时后可显著（P<0.001）降低眼内压。普通 Eudragit NPs 不会引起兔眼炎症和/或不适，也不会影响眼内压，证明其安全性和非刺激性。
