Bhattaccharjee Sonalika, Beck-Broichsitter Moritz, Banga Ajay K
Center for Drug Delivery and Research, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA.
MilliporeSigma a Business of Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany.
Pharmaceutics. 2020 May 21;12(5):472. doi: 10.3390/pharmaceutics12050472.
Although used widely in cosmetic formulations, topical delivery of niacinamide (LogP = -0.35) is unfavorable by conventional means. Poly(lactide--glycolide) (PLGA) formulations, can undergo a sol-gel transition triggered by solvent exchange, entrapping molecules and sustaining their release. The current study aims to exploit the ability of PLGA to gel in situ and enhance the topical delivery of niacinamide in microporated skin. In vitro drug permeation studies were performed using vertical Franz diffusion cells. Microporation was performed using Dr. Pen Ultima A6, where pre-treatment with a 1 mm needle-length for 10 s and a 0.5 mm needle-length for 5 s, both at 13,000 insertions/min were compared. The effect of different grades of PLGA, EXPANSORB DLG 50-2A ("low" molecular weight), and EXPANSORB DLG 50-8A ("high" molecular weight) on topical delivery was also determined. Formulations containing PLGA resulted in successful gelation in situ on application over microporated skin. A significantly higher amount of drug was found in the skin with the 0.5 mm treatment for 5 s (892 ± 36 µg/cm) than with 1 mm for 10 s (167 ± 16 µg/cm). Hence, the different grades of PLGA were evaluated with 0.5 mm, 5 s treatment, and a significantly larger amount was seen in skin with the higher rather than the lower molecular weight polymer (172 ± 53 µg/cm).
尽管烟酰胺（LogP = -0.35）在化妆品配方中广泛使用，但通过传统方式进行局部给药并不理想。聚（丙交酯-乙交酯）（PLGA）制剂可通过溶剂交换引发溶胶-凝胶转变，从而包裹分子并持续释放它们。本研究旨在利用PLGA原位凝胶化的能力，增强烟酰胺在微孔皮肤中的局部给药效果。使用垂直式Franz扩散池进行体外药物渗透研究。使用Dr. Pen Ultima A6进行微孔化处理，比较了在13,000次插入/分钟的速度下，分别用1毫米针长处理10秒和0.5毫米针长处理5秒的预处理效果。还测定了不同等级的PLGA，即EXPANSORB DLG 50-2A（“低”分子量）和EXPANSORB DLG 50-8A（“高”分子量）对局部给药的影响。含有PLGA的制剂在应用于微孔皮肤时成功实现了原位凝胶化。发现用0.5毫米处理5秒的皮肤中药物含量（892±36微克/平方厘米）明显高于用1毫米处理10秒的皮肤（167±16微克/平方厘米）。因此，对不同等级的PLGA进行了0.5毫米、5秒处理的评估，并且在使用较高分子量聚合物的皮肤中观察到的药物量明显大于较低分子量聚合物（172±53微克/平方厘米）。
