Luppi Barbara, Bigucci Federica, Cerchiara Teresa, Mandrioli Roberto, Di Pietra Anna Maria, Zecchi Vittorio
Department of Pharmaceutical Sciences, University of Bologna, Via S. Donato 19/2, Bologna, Italy.
Int J Pharm. 2008 Jun 24;358(1-2):44-9. doi: 10.1016/j.ijpharm.2008.02.009. Epub 2008 Feb 16.
Nano and micro preparative technologies for the realization of pharmaceutical carriers represent an actual strategy for reaching the therapeutic success of drugs, particularly in the case of peptidic drugs. Vancomycin is here entrapped in carriers composed by a swellable, mucoadhesive and biodegradable albumin core, coated with fatty acids able to improve a colon-specific release. Bovine serum albumin nanospheres (core) were prepared from protein solutions using a coacervation method followed by thermal cross-linking at different temperature, or from protein solutions at different pHs using a coacervation method followed by thermal cross-linking at 75 degrees C. Solid nanospheres were collected by freeze-drying, loaded by soaking from solutions of vancomycin and subsequently coated with myristic, palmitic or stearic acid by spray-drying technique obtaining microcapsules. Nanosphere dimensions and polydispersity, drug loading capacity, swelling ability and mucoadhesion properties were evaluated, as well as in vitro release behaviour. The results indicated that nanospheres present an adequate loading capacity, a great swelling tendency and good mucoadhesion ability. Moreover, albumin cores showed a pH-dependent release according to the structure of thermally denaturated protein in different experimental conditions, while microcapsules showed a pH-dependent release according to the different fatty acids solubility in acidic and alkaline media.
用于实现药物载体的纳米和微米制备技术是实现药物治疗成功的一种切实可行的策略，尤其是对于肽类药物而言。在此，万古霉素被包裹于由可溶胀、粘膜粘附且可生物降解的白蛋白核心组成的载体中，该核心涂覆有能够改善结肠特异性释放的脂肪酸。牛血清白蛋白纳米球（核心）由蛋白质溶液通过凝聚法制备，随后在不同温度下进行热交联，或者由处于不同pH值的蛋白质溶液通过凝聚法制备，随后在75℃下进行热交联。通过冷冻干燥收集固体纳米球，通过从万古霉素溶液中浸泡进行负载，随后通过喷雾干燥技术用肉豆蔻酸、棕榈酸或硬脂酸进行包衣，从而获得微胶囊。评估了纳米球尺寸和多分散性、载药量、溶胀能力和粘膜粘附特性以及体外释放行为。结果表明，纳米球具有足够的载药量、较大的溶胀趋势和良好的粘膜粘附能力。此外，在不同实验条件下，白蛋白核心根据热变性蛋白质的结构呈现出pH依赖性释放，而微胶囊则根据不同脂肪酸在酸性和碱性介质中的溶解度呈现出pH依赖性释放。
