Habib Rukhshanda, Azad Abul Kalam, Akhlaq Muhammad, Al-Joufi Fakhria A, Shahnaz Gul, Mohamed Hanan R H, Naeem Muhammad, Almalki Abdulraheem S A, Asghar Junaid, Jalil Aamir, Abdel-Daim Mohamed M
Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan.
Department of Pharmacology, University of Oxford, Mansfield Rd., Oxford OX1 3QT, UK.
Polymers (Basel). 2022 Jan 20;14(3):415. doi: 10.3390/polym14030415.
In this study, a first attempt has been made to deliver levosulpiride transdermally through a thiolated chitosan microneedle patch (TC-MNP). Levosulpiride is slowly and weakly absorbed from the gastrointestinal tract with an oral bioavailability of less than 25% and short half-life of about 6 h. In order to enhance its bioavailability, levosulpiride-loaded thiolated chitosan microneedle patches (LS-TC-MNPs) were fabricated. Firstly, thiolated chitosan was synthesized and characterized by nuclear magnetic resonance (HNMR) spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Thiolated chitosan has been used in different drug delivery systems; herein, thiolated chitosan has been used for the transdermal delivery of LS. LS-TC-MNPs were fabricated from different concentrations of thiolated chitosan solution. Furthermore, the levosulpiride-loaded thiolated chitosan microneedle patch (LS-TC-MNP) was characterized by FTIR spectroscopic analysis, scanning electron microscopy (SEM) study, penetration ability, tensile strength, moisture content, patch thickness, and elongation test. LS-TC-MNP fabricated with 3% thiolated chitosan solution was found to have the best tensile strength, moisture content, patch thickness, elongation, drug-loading efficiency, and drug content. Thiolated chitosan is biodegradable, nontoxic and has good absorption and swelling in the skin. LS-TC-MNP-3 consists of 100 needles in 10 rows each with 10 needles. The length of each microneedle was 575 μm; they were pyramidal in shape, with sharp pointed ends and a base diameter of 200 µm. The microneedle patch (LS-TC-MNP-3) resulted in-vitro drug release of 65% up to 48 h, ex vivo permeation of 63.6%, with good skin biocompatibility and enhanced in-vivo pharmacokinetics (AUC = 986 µg/mL·h, Cmax = 24.5 µg/mL) as compared to oral LS dispersion (AUC = 3.2 µg/mL·h, Cmax = 0.5 µg/mL). Based on the above results, LS-TC-MNP-3 seems to be a promising strategy for enhancing the bioavailability of levosulpiride.
在本研究中，首次尝试通过硫醇化壳聚糖微针贴剂（TC-MNP）经皮递送左舒必利。左舒必利从胃肠道吸收缓慢且微弱，口服生物利用度低于25%，半衰期约为6小时。为提高其生物利用度，制备了载左舒必利的硫醇化壳聚糖微针贴剂（LS-TC-MNPs）。首先，通过核磁共振（HNMR）光谱、衰减全反射傅里叶变换红外（ATR-FTIR）光谱、差示扫描量热法（DSC）和X射线衍射（XRD）对合成的硫醇化壳聚糖进行表征。硫醇化壳聚糖已用于不同的药物递送系统；在此，硫醇化壳聚糖用于左舒必利的经皮递送。由不同浓度的硫醇化壳聚糖溶液制备LS-TC-MNPs。此外，通过FTIR光谱分析、扫描电子显微镜（SEM）研究、渗透能力、拉伸强度、水分含量、贴剂厚度和伸长率测试对载左舒必利的硫醇化壳聚糖微针贴剂（LS-TC-MNP）进行表征。发现用3%硫醇化壳聚糖溶液制备的LS-TC-MNP具有最佳的拉伸强度、水分含量、贴剂厚度、伸长率、载药效率和药物含量。硫醇化壳聚糖可生物降解、无毒，在皮肤中具有良好的吸收和溶胀性。LS-TC-MNP-3由10排共100根针组成，每根微针长度为575μm；它们呈金字塔形，尖端尖锐，基部直径为200μm。微针贴剂（LS-TC-MNP-3）在48小时内的体外药物释放率为65%，离体渗透率为63.6%，具有良好的皮肤生物相容性，与口服左舒必利分散体相比（AUC = 3.2μg/mL·h，Cmax = 0.5μg/mL），体内药代动力学得到改善（AUC = 986μg/mL·h，Cmax = 24.5μg/mL）。基于上述结果，LS-TC-MNP-3似乎是提高左舒必利生物利用度的一种有前景的策略。
