Singla Pankaj, Singh Onkar, Sharma Shagun, Betlem Kai, Aswal Vinod K, Peeters Marloes, Mahajan Rakesh Kumar
Department of Chemistry, UGC-Centre for Advanced Studies-I, Guru Nanak Dev University, Amritsar 143005, India.
Faculty of Science and Engineering, Division of Chemistry and Environmental Sciences, Manchester Metropolitan University, John Dalton Building, Chester Street, Manchester M15 6BH, U.K.
ACS Omega. 2019 Jun 28;4(6):11251-11262. doi: 10.1021/acsomega.9b00939. eCollection 2019 Jun 30.
Pluronics (tri-block copolymers) have a significant role in the pharmaceutical industry and are being used to enhance the solubility and delivery of hydrophobic drugs in different marketed formulations. However, instability and unsatisfactory drug-loading capacity are the major weak spots of these pluronic micelles. The present research work is designed to solve the existing issues by the solubilization study of hydrophobic drugs in different pluronic micelles at variable temperatures. The solubilization of the hydrophobic antiepileptic drug lamotrigine (LAM) in five different pluronic micelles viz. P84, P85, F127, F108, and F68 was studied at different temperatures, 37, 47, and 57 °C, using UV-visible spectroscopy. The solubilization of LAM in pluronic micelles increased with the increase in temperature. Small-angle neutron scattering (SANS) measurements were used to observe the morphological and structural changes taking place in pluronics by increasing the temperature. The SANS results showed the morphological changes of spherical P84 micelles to prolate ellipsoidal micelles at 57 °C due to remarkable increase in the aggregation number. This morphological conversion was further confirmed by the heat transfer method (HTM) and dynamic light scattering (DLS) measurements. DLS measurements confirmed that LAM-loaded micelles showed a greater hydrodynamic diameter ( ) compared to unloaded micelles, assuring LAM solubilization in the pluronic micelles. The rate of controlled release of LAM from five different pluronic micelles was accessed by using different kinetic models to evaluate the in vitro release profile. This is the first report in which HTM measurements are established for the analysis of morphological changes in the thermoresponsive pluronic micelles in real time. The present work corroborates how we can control the drug-loading capacity, morphological structure of the drug carrier, as well as drug release by simply changing the temperature of pluronic micellar media.
普朗尼克（三嵌段共聚物）在制药行业中发挥着重要作用，正被用于提高不同市售制剂中疏水性药物的溶解度和递送效率。然而，不稳定性和不理想的载药量是这些普朗尼克胶束的主要弱点。本研究旨在通过研究不同普朗尼克胶束在不同温度下对疏水性药物的增溶作用来解决现有问题。使用紫外可见光谱法，研究了疏水性抗癫痫药物拉莫三嗪（LAM）在五种不同的普朗尼克胶束，即P84、P85、F127、F108和F68中，于37、47和57°C不同温度下的增溶情况。LAM在普朗尼克胶束中的增溶作用随温度升高而增强。利用小角中子散射（SANS）测量来观察随着温度升高普朗尼克胶束中发生的形态和结构变化。SANS结果表明，由于聚集数显著增加，球形P84胶束在57°C时转变为长椭球形胶束。这种形态转变通过传热法（HTM）和动态光散射（DLS）测量得到进一步证实。DLS测量证实，与未载药胶束相比，载有LAM的胶束表现出更大的流体动力学直径（ ），确保了LAM在普朗尼克胶束中的增溶。通过使用不同的动力学模型评估体外释放曲线，研究了LAM从五种不同普朗尼克胶束中的控释速率。这是首次建立HTM测量用于实时分析热响应性普朗尼克胶束形态变化的报告。本研究证实了我们如何能够通过简单改变普朗尼克胶束介质的温度来控制载药量、药物载体的形态结构以及药物释放。
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