苯甲酸利扎曲坦原位鼻凝胶纳米结构脂质载体的制备与表征。

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Assay and drug development technologies Pub Date : 2022-07-01 Epub Date: 2022-06-30 DOI:10.1089/adt.2022.044
Dyandevi Mathure, Hemantkumar Ranpise, Rajendra Awasthi, Atmaram Pawar
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引用次数: 7

摘要

鼻内途径提供大的表面积,避免第一过代谢,并导致改善药物吸收。鼻内给药的目标是药物到大脑治疗中枢神经疾病,如偏头痛。本研究的目的是制备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,并采用32因子设计优化。优化后的NLCs为球形,粒径为189 nm,包封率为84.5%,24 h释药率为83.9%。将负载rb的NLCs纳入液体Carbopol 934P和Poloxamer 407凝胶体系中,以获得原位凝胶形成。对所得产品进行了胶凝能力、粘度和粘接强度的评估。体内药代动力学研究显示,经鼻给药后脑内药物浓度显著升高,Cmax值为5.1 ng/mL,曲线下面积为829 ng/(min·mL)。RB-NLCs原位鼻腔凝胶的鼻到脑靶向参数,即药物靶向指数(2.76)和鼻到脑药物直接转运(63.69%)均显著升高,证实了药物经鼻途径靶向脑。体外鼻毒性研究未显示对鼻黏膜有毒性。因此,脂质载体原位凝胶的应用证明了鼻内递送RB的潜力,而不是传统的凝胶配方,可以有效地靶向大脑。
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Formulation and Characterization of Nanostructured Lipid Carriers of Rizatriptan Benzoate-Loaded In Situ Nasal Gel for Brain Targeting.

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 Cmax 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.

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来源期刊
Assay and drug development technologies
Assay and drug development technologies 医学-生化研究方法
CiteScore
3.60
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts
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