Department of Pharmaceutical Sciences, Bologna University, Via San Donato 19/2, Bologna, Italy.
Eur J Pharm Sci. 2011 Nov 20;44(4):559-65. doi: 10.1016/j.ejps.2011.10.002. Epub 2011 Oct 8.
Peroral administration of tacrine, the first acetylcholinestearse inhibitor licensed for the treatment of Alzheimer's disease, is associated with low bioavailability, due to an extended first-pass methabolism, short elimination half-life and hepatotoxicity. Nasal drug delivery may reduce the degree of these problems. Tacrine hydrochloride nasal delivery is here investigated by means of albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin). Bovine serum albumin nanoparticles were obtained using a coacervation method, followed by thermal cross-linking, starting from protein solution at alkaline pH. After preparation, nanoparticles were loaded by soaking from solutions of tacrine hydrochloride and lyophilised. Thermal analysis (differential scanning calorimetry and thermogravimetric analysis) supported by Fourier Transform Infrared Spectroscopy were performed in order to confirm protein cross-linking in nanosphere structure and possible drug/carrier interaction occurred after the loading process. Moreover, size, polydispersity, zeta potential and morphology of the nanoparticles were investigated as well as drug loading, mucoadhesion properties and ex-vivo drug permeation ability. Results indicate that all the nanoparticles presented a mean size and a polydispersity lower than 300nm and 0.33nm, respectively, were spherical shaped and negatively charged even after drug loading. Moreover, the presence of the different beta cyclodextrins in the polymeric network affected drug loading and could differently modulate nanoparticle mucoadhesiveness and drug permeation behaviour.
他克林（一种用于治疗老年痴呆症的乙酰胆碱酯酶抑制剂）经口给药的生物利用度低，这是由于其首过代谢延长、消除半衰期短和肝毒性所致。鼻腔给药可能会降低这些问题的严重程度。本研究采用载有β-环糊精和两种不同β-环糊精衍生物（羟丙基β-环糊精和磺丁基醚β-环糊精）的白蛋白纳米粒来研究盐酸他克林的鼻腔给药。牛血清白蛋白纳米粒通过共凝聚法，在碱性 pH 值的蛋白溶液中进行热交联来制备。制备后，通过从盐酸他克林溶液中浸泡和冷冻干燥来负载纳米粒。通过傅里叶变换红外光谱对热分析（差示扫描量热法和热重分析）进行支持，以确认纳米球结构中的蛋白质交联以及负载过程后可能发生的药物/载体相互作用。此外，还研究了纳米粒的粒径、多分散性、Zeta 电位和形态，以及载药量、黏膜黏附特性和体外药物渗透能力。结果表明，所有纳米粒的平均粒径和多分散性均低于 300nm 和 0.33nm，呈球形且带负电荷，即使在负载药物后也是如此。此外，聚合物网络中不同β-环糊精的存在会影响药物载药量，并可不同程度地调节纳米粒的黏膜黏附性和药物渗透行为。
