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脂质体干粉制剂的最新进展:制备与评价

Recent advances in liposomal dry powder formulations: preparation and evaluation.

作者信息

Misra Ambikanandan, Jinturkar Kaustubh, Patel Deepa, Lalani Jigar, Chougule Mahavir

机构信息

The Maharaja Sayajirao University of Baroda, Department of Pharmacy, Kalabhavan, Vadodara, Gujarat State, India.

出版信息

Expert Opin Drug Deliv. 2009 Jan;6(1):71-89. doi: 10.1517/17425240802652309.

Abstract

Liposomal drug dry powder formulations have shown many promising features for pulmonary drug administration, such as selective localization of drug within the lung, controlled drug release, reduced local and systemic toxicities, propellant-free nature, patient compliance, high dose carrying capacity, stability and patent protection. Critical review of the recent developments will provide a balanced view on benefits of liposomal encapsulation while developing dry powder formulations and will help researchers to update themselves and focus their research in more relevant areas. In liposomal dry powder formulations (LDPF), drug encapsulated liposomes are homogenized, dispersed into the carrier and converted into dry powder form by using freeze drying, spray drying and spray freeze drying. Alternatively, LDPF can also be formulated by supercritical fluid technologies. On inhalation with a suitable inhalation device, drug encapsulated liposomes get rehydrated in the lung and release the drug over a period of time. The prepared LDPF are evaluated in vitro and in vivo for lung deposition behavior and drug disposition in the lung using a suitable inhaler device. The most commonly used liposomes are composed of lung surfactants and synthetic lipids. Delivery of anticancer agents for lung cancer, corticosteroids for asthma, immunosuppressants for avoiding lung transplantation rejection, antifungal drugs for lung fungal infections, antibiotics for local pulmonary infections and cystic fibrosis and opioid analgesics for pain management using liposome technology are a few examples. Many liposomal formulations have reached the stage of clinical trials for the treatment of pulmonary distress, cystic fibrosis, lung fungal infection and lung cancer. These formulations have given very promising results in both in vitro and in vivo studies. However, modifications to new therapies for respiratory diseases and systemic delivery will provide new challenges in conducting well-designed inhalation toxicology studies to support these products, especially for chronic diseases.

摘要

脂质体药物干粉制剂在肺部给药方面展现出许多有前景的特性,例如药物在肺内的选择性定位、可控的药物释放、局部和全身毒性的降低、无推进剂特性、患者依从性、高剂量承载能力、稳定性以及专利保护。对近期进展进行批判性综述将在开发干粉制剂时对脂质体包封的益处提供一个平衡的观点,并有助于研究人员更新知识,将研究重点聚焦于更相关的领域。在脂质体干粉制剂(LDPF)中,药物包封的脂质体被均质化,分散到载体中,并通过冷冻干燥、喷雾干燥和喷雾冷冻干燥转化为干粉形式。另外,LDPF也可以通过超临界流体技术来制备。使用合适的吸入装置吸入时,药物包封的脂质体在肺中重新水化,并在一段时间内释放药物。所制备的LDPF使用合适的吸入器装置在体外和体内评估其肺部沉积行为和肺内药物处置情况。最常用的脂质体由肺表面活性剂和合成脂质组成。使用脂质体技术递送用于肺癌的抗癌药物、用于哮喘的皮质类固醇、用于避免肺移植排斥的免疫抑制剂、用于肺部真菌感染的抗真菌药物、用于局部肺部感染和囊性纤维化的抗生素以及用于疼痛管理的阿片类镇痛药等就是一些例子。许多脂质体制剂已进入治疗肺部窘迫、囊性纤维化、肺部真菌感染和肺癌的临床试验阶段。这些制剂在体外和体内研究中都给出了非常有前景的结果。然而,对呼吸系统疾病新疗法和全身给药的改进将在开展精心设计的吸入毒理学研究以支持这些产品方面带来新挑战,尤其是对于慢性病。

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