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 3² 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 C_max 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.

中文翻译：

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用于脑靶向的利扎曲坦苯甲酸酯原位鼻凝胶纳米结构脂质载体的制备和表征

鼻内途径提供大表面积，避免首过代谢，并导致药物吸收改善。鼻内给药将药物靶向大脑，用于治疗偏头痛等中枢神经疾病。该研究的目的是配制含有苯甲酸利扎曲坦 (RB) 负载的纳米结构脂质载体 (NLC) 的原位鼻凝胶。采用熔融乳化超声法制备 NLCs，并使用 3 ^2优化因子设计。优化后的 NLC 呈球形，粒径为 189 nm，药物包封率高（84.5%），24 小时后药物释放率为 83.9%。将负载 RB 的 NLC 掺入液体 Carbopol 934P 和 Poloxamer 407 液体胶凝系统中以获得原位凝胶形成。评估所得产品的胶凝能力、粘度和粘膜粘附强度。体内药代动力学研究显示，在C _max鼻内给药后，大脑中药物的显着治疗浓度值为5.1 ng/mL，曲线下面积值为829 ng/(min·mL)。RB-NLCs原位鼻凝胶的鼻到脑靶向参数值显着较高，即药物靶向指数（2.76）和鼻到脑药物直接转运（63.69%），证实了药物通过鼻途径靶向脑。体外鼻毒性研究显示对鼻粘膜没有毒性迹象。因此，与常规凝胶制剂相比，负载脂质载体的原位凝胶的应用证明了在鼻内递送RB的潜力，以实现有效的脑靶向。