Kadir F, Eling W M, Abrahams D, Zuidema J, Crommelin D J
Department of Pharmaceutics, The Netherlands, University of Utrecht.
Int J Clin Pharmacol Ther Toxicol. 1992 Oct;30(10):374-82.
Liposomes are effective carrier systems for prolonged drug release. As all other drug formulations for parenteral use, the safety of liposomal formulations should be established before clinical application. In this study, some safety aspects of intramuscularly injected (single dose) "gel-state" type liposomes and the ability of liposome encapsulation to diminish irritating effects of intramuscularly applied drugs were studied by histopathological analysis over a period of 14 days in mice. Injection of saline solution showed no tissue reaction at the injection site. Intramuscular injection of liposomes alone showed an infiltrative reaction consisting of a population of macrophages. Within this population fat cells were present. In time, the population of macrophages present at the injection site was largely replaced by loose connective tissue. Novaminsulfon (NS) injected intramuscularly in "free" form is a strongly irritating drug, causing hemorrhage, cell necrosis, inflammatory reactions and eventually fibrosis. However, NS being encapsulated in liposomes was hardly more irritating than liposomes alone. The same was true for liposome-encapsulated chloroquine and free chloroquine. When sustained-release of a drug is therapeutically desirable, the parenteral application of a liposome-encapsulated formulation can be considered for drugs, in particular for those drugs causing tissue injury at the injection site.
脂质体是用于延长药物释放的有效载体系统。与所有其他用于肠胃外给药的药物制剂一样，脂质体制剂的安全性应在临床应用前确定。在本研究中，通过组织病理学分析，在14天的时间里研究了肌肉注射（单剂量）“凝胶态”型脂质体的一些安全性方面，以及脂质体包封减少肌肉注射药物刺激性作用的能力。注射生理盐水在注射部位未显示组织反应。单独肌肉注射脂质体显示出由一群巨噬细胞组成的浸润性反应。在这群细胞中存在脂肪细胞。随着时间的推移，注射部位的巨噬细胞群体大部分被疏松结缔组织取代。以“游离”形式肌肉注射的新胂凡纳明（NS）是一种强刺激性药物，会导致出血、细胞坏死、炎症反应并最终形成纤维化。然而，包封在脂质体中的NS几乎不比单独的脂质体更具刺激性。脂质体包封的氯喹和游离氯喹也是如此。当药物的缓释在治疗上是可取的时，对于那些在注射部位会引起组织损伤的药物，可考虑肠胃外应用脂质体包封制剂。
