Mathure Dyandevi, Ranpise Hemantkumar, Awasthi Rajendra, Pawar Atmaram
Bharati Vidyappeth's Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India.
Abhinav Education Society's College of Pharmacy, Pune, Maharashtra, India.
Assay Drug Dev Technol. 2022 Jul;20(5):211-224. doi: 10.1089/adt.2022.044. Epub 2022 Jun 30.
Intranasal route provides large surface area, avoids first-pass metabolism, and results in improved drug absorption. Intranasal delivery targets the drug to the brain for treatment of central nervous diseases viz migraine. The objective of the study was to formulate in situ nasal gel containing rizatriptan benzoate (RB)-loaded nanostructured lipid carriers (NLCs). NLCs were prepared by melt-emulsification ultrasonication method and optimized using 3 factorial design. Optimized NLCs were spherical with particle size of 189 nm, high drug encapsulation efficiency (84.5%), and 83.9% drug release at the end of 24 h. RB-loaded NLCs were incorporated into the liquid Carbopol 934P and Poloxamer 407 liquid gelling system to obtain in situ gel formation. The resultant product was assessed for gelling capacity, viscosity, and mucoadhesive strength. In vivo pharmacokinetic studies revealed significant therapeutic concentration of drug in the brain following intranasal administration with value of 5.1 ng/mL and area under the curve value of 829 ng/(min·mL). Significantly higher values of nose to brain targeting parameters, namely, drug targeting index (2.76) and nose to brain drug direct transport (63.69%) for RB-NLCs in situ nasal gel, confirmed drug targeting to brain through nasal route. The ex vivo nasal toxicity study showed no sign of toxicity to the nasal mucosa. Thus, the application of lipid carrier-loaded in situ gel proved potential for intranasal delivery of RB over the conventional gel formulations for efficient brain targeting.
鼻内给药途径具有较大的表面积，可避免首过代谢，并能提高药物吸收。鼻内给药可将药物靶向输送至脑部，用于治疗中枢神经系统疾病，如偏头痛。本研究的目的是制备含苯甲酸利扎曲普坦（RB）的纳米结构脂质载体（NLCs）的原位鼻用凝胶。通过熔融乳化超声法制备NLCs，并采用三因素设计进行优化。优化后的NLCs呈球形，粒径为189 nm，药物包封率高（84.5%），24小时结束时药物释放率为83.9%。将载有RB的NLCs加入液态卡波姆934P和泊洛沙姆407液体胶凝系统中，以形成原位凝胶。对所得产品的胶凝能力、粘度和粘膜粘附强度进行了评估。体内药代动力学研究表明，鼻内给药后脑中药物浓度达到显著治疗浓度，其值为5.1 ng/mL，曲线下面积值为829 ng/(min·mL)。RB-NLCs原位鼻用凝胶的鼻脑靶向参数，即药物靶向指数（2.76）和鼻脑药物直接转运率（63.69%）显著更高，证实了药物可通过鼻内途径靶向输送至脑部。体外鼻毒性研究表明对鼻黏膜无毒性迹象。因此，与传统凝胶制剂相比，脂质载体负载的原位凝胶在鼻内递送RB以实现高效脑靶向方面具有潜在应用价值。
