Bostanudin Mohammad F, Barbu Eugen, Liew Kai Bin
College of Pharmacy, Al Ain University, Abu Dhabi 112612, United Arab Emirates.
School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, Portsmouth PO1 2DT, UK.
Polymers (Basel). 2021 Aug 25;13(17):2852. doi: 10.3390/polym13172852.
Polymeric colloidal nanocarriers formulated from hydrophobically grafted carbohydrates have been the subject of intensive research due to their potential to increase the percutaneous penetration of hydrophilic actives. To this goal, a series of hydrophobically grafted pullulan (BMO-PUL) derivatives with varying degree of grafting (5-64%) was prepared through functionalisation with 2-(butoxymethyl)oxirane. The results demonstrated that monodispersed BMO-PUL nanocarriers (size range 125-185 nm) could be easily prepared via nanoprecipitation; they exhibit close-to-spherical morphology and adequate stability at physiologically relevant pH. The critical micellar concentration of BMO-PUL was found to be inversely proportional to their molecular weight (Mw) and degree of grafting (DG), with values of 60 mg/L and 40 mg/L for DG of 12.6% and 33.8%, respectively. The polymeric nanocarriers were loaded with the low Mw hydrophilic active α-arbutin (16% loading), and the release of this active was studied at varying pH values (5 and 7), with a slightly faster release observed in acidic conditions; the release profiles can be best described by a first-order kinetic model. In vitro investigations of BMO-PUL nanocarriers (concentration range 0.1-4 mg/mL) using immortalised skin human keratinocytes cells (HaCaT) evidenced their lack of toxicity, with more than 85% cell viability after 24 h. A four-fold enhance in arbutin permeation through HaCaT monolayers was recorded when the active was encapsulated within the BMO-PUL nanocarriers. Altogether, the results obtained from the in vitro studies highlighted the potential of BMO-PUL nanocarriers for percutaneous delivery applications, which would warrant further investigation in vivo.
由疏水接枝碳水化合物制备的聚合物胶体纳米载体因其具有提高亲水性活性成分经皮渗透的潜力而成为深入研究的对象。为实现这一目标，通过用2-(丁氧基甲基)环氧乙烷进行功能化反应，制备了一系列接枝度不同（5-64%）的疏水接枝普鲁兰多糖（BMO-PUL）衍生物。结果表明，通过纳米沉淀法可轻松制备单分散的BMO-PUL纳米载体（尺寸范围为125-185 nm）；它们呈现接近球形的形态，在生理相关pH值下具有足够的稳定性。发现BMO-PUL的临界胶束浓度与它们的分子量（Mw）和接枝度（DG）成反比，接枝度为12.6%和33.8%时，临界胶束浓度分别为60 mg/L和40 mg/L。聚合物纳米载体负载了低Mw的亲水性活性成分α-熊果苷（负载量为16%），并在不同pH值（5和7）下研究了该活性成分的释放情况，在酸性条件下观察到释放速度稍快；释放曲线可用一级动力学模型最好地描述。使用永生化的人皮肤角质形成细胞（HaCaT）对BMO-PUL纳米载体（浓度范围为0.1-4 mg/mL）进行的体外研究证明它们没有毒性，24小时后细胞活力超过85%。当活性成分被封装在BMO-PUL纳米载体内时，通过HaCaT单层的熊果苷渗透增强了四倍。总之，体外研究获得的结果突出了BMO-PUL纳米载体在经皮给药应用中的潜力，这值得在体内进行进一步研究。
