Intranasal Delivery of Cetrorelix Via Lipid Liquid Crystal Nanoparticles: Characterization and Pharmacokinetic Studies in Rats.

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Soheil Tafazzoli Mehrjardi, Mohsen Tafaghodi, Saba Malek, Davood Yari, Amir Hooshang Mohammadpour, Hossein Kamali, Ali Nokhodchi
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引用次数: 0

Abstract

Nasal sprays are extensively researched due to their rapid absorption, high bioavailability, and low side effects. Lipid liquid crystal nanoparticles (LLCNs) are being considered as potential carriers for intranasal delivery. LLCs loaded with cetrorelix (GnRH antagonist) were utilized for intranasal drug delivery to enhance brain targeting while minimizing systemic exposure. A single-phase formulation incorporating HPMC as a mucoadhesive was developed to extend nasal residence time. Following intranasal administration of cetrorelix in rats, its distribution in various brain regions and serum was assessed using LC-MS-MS. In the LLC formulation, the particle diameter, PDI, and Zeta potential were measured as 204.92 ± 0.89 nm, 0.188 ± 0.019, and -21.63 ± 1.72 mV, respectively. A monomodal distribution and low polydispersity index were observed, along with a negative zeta potential. Cetrorelix was released from the LLC in a biphasic profile, with an initial burst release of 30%, followed by a gradual and sustained release phase. The LLCs containing cetrorelix exhibited lower cytotoxicity compared to the LLC base. The nasal administration of cetrorelix via LLCs presents a promising advancement for nose-to-brain drug transport. The pharmacokinetic data demonstrated that the AUC0-360min for brain tissue analysis, following nasal administration of the single-phase formulation, was 3.104 ng/ml.min. The value was 7.104 ng/ml.min for LLC nasal administration and 6.104 ng/ml.min for subcutaneous injection. The maximum concentration (Cmax) values for brain tissue analysis indicated a significant increase with LLC nasal administration (238 ± 6. 2 ng/ml) in comparison to the single-phase formulation (202.5 ± 6.3 ng/ml) and subcutaneous injection (218.2 ± 3. 1 ng/ml). In serum analysis, the Cmax values were significantly elevated, with subcutaneous injection achieving (4983.3 ± 2.5 ng/ml), followed by LLC nasal administration at (93.1 ± 6.2 ng/ml), and the single-phase formulation at (43.7 ± 2.2 ng/ml). This innovative method aims to target the brain directly, eliminating the need for needles, and reducing adverse effects, hence offering new hope for brain-targeted drug delivery. This study introduces, for the first time, a cetrorelix-loaded lipid liquid crystal (LLC) nanoparticle formulation for intranasal nose-to-brain delivery. The LLC system achieved enhanced brain targeting efficiency while reducing systemic exposure compared to conventional subcutaneous injections and simple nasal formulations, representing a promising advancement in GnRH drug delivery strategies.

脂质液晶纳米颗粒经鼻给药头孢瑞克:表征和大鼠药代动力学研究。
鼻腔喷雾剂因其吸收快、生物利用度高、副作用小而被广泛研究。脂质液晶纳米颗粒(LLCNs)被认为是鼻内给药的潜在载体。装载cetrorelix (GnRH拮抗剂)的llc用于鼻内给药,以增强脑靶向性,同时最大限度地减少全身暴露。研制了一种以HPMC为黏合剂的单相配方,以延长鼻腔停留时间。大鼠经鼻给药后,采用液相色谱-质谱联用技术(LC-MS-MS)测定其在各脑区和血清中的分布。在LLC配方中,粒径为204.92±0.89 nm, PDI为0.188±0.019,Zeta电位为-21.63±1.72 mV。观察到单峰分布和低多分散指数,以及负zeta电位。Cetrorelix以双相释放方式从LLC释放,初始释放量为30%,随后是一个逐渐持续的释放阶段。与含有cetrorelix的LLC碱相比,含有cetrorelix的LLC碱表现出较低的细胞毒性。通过llc鼻部给药cetrorelix为鼻到脑药物运输提供了一个有前途的进展。药代动力学数据显示,经鼻腔给药后,脑组织分析的AUC0-360min为3.104 ng/ml.min。值为7.104 ng/ml。最小剂量为6.104 ng/ml。皮下注射最小。脑组织分析的最大浓度(Cmax)值显示,LLC鼻给药显著增加(238±6)。2 ng/ml),而单相制剂(202.5±6.3 ng/ml)和皮下注射(218.2±3 ng/ml)。1 ng / ml)。在血清分析中,Cmax值显著升高,皮下注射达到(4983.3±2.5 ng/ml),其次是有限责任公司鼻腔给药为(93.1±6.2 ng/ml),单相给药为(43.7±2.2 ng/ml)。这种创新的方法旨在直接针对大脑,消除了对针头的需求,减少了副作用,从而为脑靶向药物递送提供了新的希望。本研究首次介绍了一种负载cetrorelix的脂质液晶(LLC)纳米颗粒配方,用于经鼻至脑给药。与传统的皮下注射和简单的鼻腔配方相比,LLC系统实现了增强的脑靶向效率,同时减少了全身暴露,代表了GnRH药物递送策略的有希望的进步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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