Faisalina A F, Sonvico Fabio, Colombo Paolo, Amirul A A, Wahab H A, Majid Mohamed Isa Abdul
Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), National Institute of Biotechnology Malaysia (NIBM), Ministry of Science, Technology and Innovation (MOSTI), Penang 11800, Malaysia.
Food and Drug Department, University of Parma, 43124 (PR) Parma, Italy.
Nanomaterials (Basel). 2020 Oct 26;10(11):2123. doi: 10.3390/nano10112123.
Polyhydroxyalkanoate (PHA) copolymers show a relatively higher in vivo degradation rate compared to other PHAs, thus, they receive a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water-soluble anticancer drug docetaxel (DCX) were produced using poly(3-hydroxybutyrate--4-hydroxybutyrate), P(3HB--4HB), copolymers biosynthesised from USMAA1020 isolated from the Malaysian environment. Three copolymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB--4HB). Blank and DCX-loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Preformulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in terms of average particle size around 150 nm and narrow particle size distribution (polydispersity index (PDI) below 0.100). The encapsulation efficiency result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX; DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticle system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug-to-polymer ratio while for the 30% and 40% drug-to-polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.
与其他聚羟基脂肪酸酯（PHA）相比，聚羟基脂肪酸酯共聚物（PHA）在体内的降解速率相对较高，因此，它们在广泛的医学应用中受到了大量关注。使用从马来西亚环境中分离出的USMAA1020生物合成的聚（3-羟基丁酸酯-4-羟基丁酸酯）[P（3HB-4HB）]共聚物制备了负载难溶性抗癌药物多西他赛（DCX）的纳米颗粒（NP）。使用了三种具有不同4-羟基丁酸酯（4HB）摩尔比例的共聚物：含16%（PHB16）、30%（PHB30）和70%（PHB70）4HB的P（3HB-4HB）。然后对空白纳米颗粒和负载DCX的纳米颗粒的尺寸和尺寸分布、表面电荷、包封率和药物释放进行了表征。处方前研究表明，通过乳化/溶剂蒸发法，使用PHB70并添加1.0%的聚乙烯醇（PVA）作为稳定剂和0.03%的维生素E-TPGS作为表面活性剂，可以实现优化的制剂。负载DCX的PHB70纳米颗粒（DCX-PHB70）在平均粒径约为150 nm且粒径分布窄（多分散指数（PDI）低于0.100）方面给出了所需的粒径分布。包封率结果表明，在药物与聚合物比例为30%w/w时：DCX-PHB16纳米颗粒能够包封高达42%的DCX；DCX-PHB30纳米颗粒包封高达46%的DCX，DCX-PHB70纳米颗粒在纳米颗粒系统中包封高达50%的DCX。对于5%、10%和20%的药物与聚合物比例，约60%的DCX在7天内从DCX-PHB70纳米颗粒中释放，而对于30%和40%的药物与聚合物比例，在孵育7天后观察到几乎完全的药物释放（98%）。
