Teixeira Maribel, Alonso Maria J, Pinto Madalena M M, Barbosa Carlos M
Centro de Estudos de Química Orgânica, Fitoquímica e Farmacologia da Universidade do Porto-Faculdade de Farmácia do Porto, Porto, Portugal.
Eur J Pharm Biopharm. 2005 Apr;59(3):491-500. doi: 10.1016/j.ejpb.2004.09.002.
The aim of the present work was to develop and characterize two different nanosystems, nanospheres and nanocapsules, containing either xanthone (XAN) or 3-methoxyxanthone (3-MeOXAN), with the final goal of improving the delivery of these poorly water-soluble compounds. The xanthones-loaded nanospheres (nanomatrix systems) and nanocapsules (nanoreservoir systems), made of poly(DL-lactide-co-glycolide) (PLGA), were prepared by the solvent displacement technique. The following characteristics of nanoparticle formulations were determined: particle size and morphology, zeta potential, incorporation efficiency, thermal behaviour, in vitro release profiles and physical stability at 4 degrees C. The nanospheres had a mean diameter <170 nm, a narrow size distribution (polydispersity index <0.1), and a negative surface charge (zeta potential <-36 mV). Their incorporation efficiencies were 33% for XAN and 42% for 3-MeOXAN. The presence of the xanthones did not affect the nanospheres size and zeta potential. DSC studies indicated that XAN and 3-MeOXAN were dispersed at a molecular level within the polymeric nanomatrix. Nanocapsules were also nanometric (mean size <300 nm) and exhibited a negative charge (zeta potential <-36 mV). Their incorporation efficiency values (>77%) were higher than those corresponding to nanospheres for both xanthones. The release of 3-MeOXAN from nanocapsules was similar to that observed for the correspondent nanoemulsion, indicating that drug release is mainly governed by its partition between the oil core and the external aqueous medium. In contrast, the release of XAN from nanocapsules was significantly slower than from the nanoemulsion, a behaviour that suggests an interaction of the drug with the polymer. Nanocapsule formulations exhibited good physical stability at 4 degrees C during a 4-month period for XAN and during a 3-month period for 3-MeOXAN.
本研究的目的是开发和表征两种不同的纳米系统，即纳米球和纳米囊，它们分别含有呫吨酮（XAN）或3-甲氧基呫吨酮（3-MeOXAN），最终目标是改善这些难溶性化合物的递送。由聚（DL-丙交酯-共-乙交酯）（PLGA）制成的负载呫吨酮的纳米球（纳米基质系统）和纳米囊（纳米储库系统）通过溶剂置换技术制备。测定了纳米颗粒制剂的以下特性：粒径和形态、zeta电位、包封率、热行为、体外释放曲线以及在４℃下的物理稳定性。纳米球的平均直径＜170nm，粒径分布窄（多分散指数＜0.1），表面带负电荷（zeta电位＜-36mV）。它们对XAN的包封率为33%，对3-MeOXAN的包封率为42%。呫吨酮的存在不影响纳米球的大小和zeta电位。差示扫描量热法（DSC）研究表明，XAN和3-MeOXAN在分子水平上分散在聚合物纳米基质中。纳米囊也是纳米级的（平均大小＜300nm），并带有负电荷（zeta电位＜-36mV）。两种呫吨酮在纳米囊中的包封率值（＞77%）均高于纳米球。纳米囊中3-MeOXAN的释放与相应纳米乳剂的释放相似，表明药物释放主要受其在油核与外部水相介质之间分配的控制。相比之下，纳米囊中XAN的释放明显慢于纳米乳剂，这种行为表明药物与聚合物之间存在相互作用。纳米囊制剂在4℃下对XAN有4个月的良好物理稳定性，对3-MeOXAN有3个月的良好物理稳定性。
