School of Pharmacy and Bioengineering, Keele University, Keele ST5 5BG, UK; College of Dentistry, University of Basrah, Basrah 61004, Iraq.
School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
Int J Pharm. 2021 May 15;601:120570. doi: 10.1016/j.ijpharm.2021.120570. Epub 2021 Apr 2.
Thermally active polymers, can respond structurally to temperature changes, making them interesting as potential drug delivery vehicles. Polymers of N-(3-aminopropyl) methacrylamide hydrochloride (APMA) are cationic with primary amine groups in their structure, which have been explored in biomedical applications via post-polymerisation modifications. In this work, we synthesised amphiphilic APMA monomers using hydrophobic pendant groups via conjugation onto their primary amine group. The pendant groups chosen in this study were palmitoyl, dansyl and cholesteryl moieties. The amphiphilic monomers were subsequently copolymerized with N-(2-hydroxypropyl)methacrylamide (HPMA) using varied monomer feed ratios resulting in a thermo-responsive system. The ability of the resultant aggregates in aqueous solution to encapsulate and liberate model drugs (e.g., propofol, griseofulvin and prednisolone) was then determined. Our data showed that the HPMA based formulations were capable of loading the model drug molecules inside their lipophilic core; HPMA-co-(APMA-Dansyl 2%) exhibited the largest drug encapsulation ability. Subsequently, poly(ethylene glycol) (PEG) was incorporated into the intrinsic polymer structure. This resulted in a more rapid drug release profile, whereby 100% of griseofulvin and prednisolone were liberated after only 4 h, which was only 5% and 10% before the PEG inclusion, respectively. Similarly, propofol showed 70% liberation from the polymer aggregate after 24 h, compared with only 30% liberation pre-PEGylation. These studies give an insight into the potential of the HMPA based amphiphiles as thermally responsive cargo carrier/release systems which could be exploited in the delivery of poorly soluble drugs.
热活性聚合物可以对温度变化做出结构响应，因此它们作为潜在的药物输送载体很有吸引力。N-(3-氨丙基)甲基丙烯酰胺盐酸盐（APMA）的聚合物在其结构中具有伯胺基团，这些基团已通过聚合后修饰在生物医学应用中得到了探索。在这项工作中，我们通过与伯胺基团共轭，使用疏水性侧基合成了两亲性的 APMA 单体。本研究中选择的侧基是棕榈酰基、丹磺酰基和胆甾基。随后，将两亲性单体与 N-(2-羟丙基)甲基丙烯酰胺（HPMA）共聚，采用不同的单体进料比，得到热敏性体系。然后确定所得水相中的聚集物包封和释放模型药物（例如丙泊酚、灰黄霉素和泼尼松龙）的能力。我们的数据表明，基于 HPMA 的制剂能够将模型药物分子包封在其亲脂性核心内；HPMA-co-(APMA-Dansyl 2%)表现出最大的药物包封能力。随后，将聚乙二醇（PEG）掺入到固有聚合物结构中。这导致了更快速的药物释放曲线，其中只有 4 小时后，100%的灰黄霉素和泼尼松龙被释放，而在包含 PEG 之前，分别为 5%和 10%。同样，丙泊酚在 24 小时后从聚合物聚集体中释放了 70%，而在 PEG 化之前仅释放了 30%。这些研究深入了解了基于 HMPA 的两亲体作为热敏性货物载体/释放系统的潜力，这些系统可用于输送难溶性药物。
