Charoongchit Pimchanok, Suksiriworapong Jiraphong, Sripha Kittisak, Mao Shirui, Sapin-Minet Anne, Maincent Philippe, Junyaprasert Varaporn Buraphacheep
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand; Center of Excellence in Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Mater Sci Eng C Mater Biol Appl. 2017 Mar 1;72:444-455. doi: 10.1016/j.msec.2016.11.043. Epub 2016 Nov 15.
Cationic copolymers have been attractive to investigate due to their potential to complexation with anionic drugs and expected to use in the pharmaceutical application. In this study, the modified poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers (P(CL)-PEG) were successfully synthesized by click reaction. The amount of small molecular cationic ligand, propargyltrimethyl ammonium iodide, was varied and grafted onto various mole ratios of P(CL) to PEG. The effects of P(CL) chain length and amount of the grafting cationic ligand on physicochemical properties of polymers and particles were studied. The number-average molecular weights of the copolymers grafted with cationic ligand were found ranging between 10,000 and 23,000g/mol as investigated by NMR. From DSC study, the results showed that the grafting ligand affected thermal behaviors of the copolymers by increasing the glass transition temperature and decreasing the melting temperature of the copolymers. Furthermore, these cationic copolymers could self-aggregate with their critical aggregation concentration depending on mole ratios of hydrophilic to hydrophobic portions. The particles containing higher amounts of the cationic ligand tended to aggregate in both acidic and basic pH environment and at high salt concentration. Additionally, particle size, size distribution (PdI), and morphology of self-assembling particles varied depending on P(CL) chain length and the amount of the grafting cationic ligand. The synthesized cationic copolymer showed a capability to encapsulate a high negatively charged drug, enoxaparin, with an encapsulation efficiency of 87%. After drug incorporation, the particles substantially changed in size, shape, PdI, and zeta potential to become more suitable for drug delivery. These cationic copolymers with flexible properties will be the candidate for further development as carriers for the delivery of negatively charged drugs.
阳离子共聚物因其与阴离子药物络合的潜力而备受研究关注，并有望应用于制药领域。在本研究中，通过点击反应成功合成了改性聚（ε-己内酯）-聚（乙二醇）共聚物（P(CL)-PEG）。改变小分子阳离子配体炔丙基三甲基碘化铵的用量，并将其接枝到不同摩尔比的P(CL)与PEG上。研究了P(CL)链长和接枝阳离子配体的量对聚合物和颗粒物理化学性质的影响。通过核磁共振研究发现，接枝阳离子配体的共聚物的数均分子量在10,000至23,000g/mol之间。差示扫描量热法研究结果表明，接枝配体通过提高共聚物的玻璃化转变温度和降低其熔点来影响共聚物的热行为。此外，这些阳离子共聚物能够以其临界聚集浓度自聚集，这取决于亲水部分与疏水部分的摩尔比。含有较高量阳离子配体的颗粒在酸性和碱性pH环境以及高盐浓度下都倾向于聚集。此外，自组装颗粒的粒径、粒径分布（PdI）和形态因P(CL)链长和接枝阳离子配体的量而异。合成的阳离子共聚物显示出能够包封高负电荷药物依诺肝素的能力，包封效率为87%。药物包封后，颗粒在尺寸、形状、PdI和zeta电位方面发生了显著变化，使其更适合药物递送。这些具有灵活性质的阳离子共聚物将成为进一步开发用于递送负电荷药物的载体的候选材料。
