Naltrexone (NTX) hydrochloride is a potent opioid antagonist with significant first-pass metabolism and notable untoward effects when administered orally or intramuscularly. Microneedle (MN)-assisted transdermal delivery is an attractive alternative that can improve therapeutic delivery to deeper skin layers. In this study, chitosan-NTX microspheres were developed via spray-drying, and their potential for transdermal NTX delivery in association with MN skin treatment was assessed. A quality-by-design approach was used to evaluate the impact of key input variables (chitosan molecular weight, concentration, chitosan-NTX ratio, and feed flow rate) on microsphere physical characteristics, encapsulation efficiency, and drug-loading capacity. Formulated microspheres had high encapsulation efficiencies (70%–87%), with drug-loading capacities ranging from 10%–43%. NTX flux through MN-treated skin was 11.6 ± 2.2 µg/cm²·h from chitosan-NTX microspheres, which was significantly higher than flux across intact skin. Combining MN-assisted delivery with the chitosan microsphere formulation enabled NTX delivery across the skin barrier, while controlling the dose released to the skin.

中文翻译：

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喷雾干燥的壳聚糖-纳曲酮微球用于微针辅助透皮给药的设计和表征。

盐酸纳曲酮（NTX）是一种有效的阿片类药物拮抗剂，具有明显的首过代谢，在口服或肌内给药时具有明显的不良作用。微针（MN）辅助的透皮递送是一种有吸引力的替代方法，可以改善对深层皮肤的治疗性递送。在这项研究中，通过喷雾干燥开发了壳聚糖-NTX微球，并评估了其与MN皮肤治疗相关的经皮NTX递送的潜力。通过设计质量方法来评估关键输入变量（壳聚糖分子量，浓度，壳聚糖-NTX比和进料流速）对微球物理特性，包封效率和载药量的影响。配制的微球具有很高的封装效率（70％–87％），载药量为10％–43％。通过MN处理的皮肤的NTX通量为11.6±2.2 µg / cm壳聚糖-NTX微球² h，明显高于完整皮肤的通量。将MN辅助递送与壳聚糖微球制剂结合使用，可使NTX跨皮肤屏障递送，同时控制释放至皮肤的剂量。