Leo Eliana, Scatturin Angelo, Vighi Eleonora, Dalpiaz Alessandro
Dipartimento di Scienze Farmaceutiche, Modena and Reggio Emilia University, via G. Campi 183, I-41100 Modena, Italy.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):3070-9. doi: 10.1166/jnn.2006.408.
We report a study evaluating the encapsulation and release modalities from poly(D,L lactic acid) (PLA) or poly(D,L-lactide-co-glicolide) (PLGA) micro- and nano-particles of the antiischemic drug N6-cyclopentyladenosine (CPA) and bovine serum albumin (BSA), chosen as protein model. The results obtained by classical preparation methods (nanoprecipitation, single or double emulsion/solvent evaporation) of the particles were compared with those obtained by their formulation with a novel method, employing a thermosensible gel of Pluronic F-127, whose aqueous solutions can be liquid when refrigerated, but gel upon warming. Our results indicate that CPA-loaded nanoparticles, obtained by classical methods, drastically reduce their drug content showing, moreover, any control of the drug release with respect to CPA-loaded microparticles. The novel preparation method allowed us to obtain, instead, CPA encapsulation values in nanoparticles similar to those obtained for microparticles, achieving also a weak control of the drug release. Any drastic reduction of BSA particle content was obtained by decreasing their size from micro- to nano-scales, independently on the employment of classical or novel preparation methods. Moreover, the size reduction induced only a weak increase of the BSA release rate. The patterns of protein released from micro- and nano-particles obtained by the same formulation method were similar. In particular, the micro- and nano-spheres prepared by double emulsion technique showed an incomplete BSA release, characterized by an elevated burst effect followed by a very slow phase. On the other hand, the release from micro- and nano-particles obtained by the novel method was complete and quite regular, being characterized by a little burst release followed by a fast phase. These results have been related to the strong BSA distribution (observed by confocal laser scanning microscope) in the surface or in the core of microparticles obtained by the classical or novel methods, respectively.
我们报告了一项研究，该研究评估了抗缺血药物N6-环戊基腺苷（CPA）和作为蛋白质模型的牛血清白蛋白（BSA）从聚（D，L-乳酸）（PLA）或聚（D，L-丙交酯-共-乙交酯）（PLGA）微米和纳米颗粒中的包封及释放方式。将通过颗粒的经典制备方法（纳米沉淀法、单乳液或双乳液/溶剂蒸发法）获得的结果与通过采用一种新方法（使用普朗尼克F-127热敏凝胶，其水溶液在冷藏时为液体，但加热后会凝胶化）进行配方制备获得的结果进行了比较。我们的结果表明，通过经典方法获得的载CPA纳米颗粒大幅降低了其药物含量，此外，与载CPA微米颗粒相比，对药物释放没有任何控制。相反，新的制备方法使我们能够在纳米颗粒中获得与微米颗粒相似的CPA包封值，同时也实现了对药物释放的微弱控制。通过将BSA颗粒尺寸从微米级减小到纳米级，无论采用经典还是新的制备方法，都能使BSA颗粒含量大幅降低。此外，尺寸减小仅使BSA释放速率略有增加。通过相同配方方法获得的微米和纳米颗粒释放蛋白质的模式相似。特别是，通过双乳液技术制备的微米和纳米球显示出BSA释放不完全，其特征是有较高的突释效应，随后是非常缓慢的阶段。另一方面，通过新方法获得的微米和纳米颗粒的释放是完全且相当规律的，其特征是有少量突释，随后是快速阶段。这些结果与分别通过经典或新方法获得的微米颗粒表面或核心中强烈的BSA分布（通过共聚焦激光扫描显微镜观察）有关。
