Raghunath Indu, Koland Marina, Saoji Suprit D, Bukke Sarad Pawar Naik, Deshpande N Shridhar, Augustin Varsha, Rarokar Nilesh, Thalluri Chandrashekar
Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Mangalore, Karnataka, 575018, India.
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, 440033, India.
Sci Rep. 2025 Jul 2;15(1):22771. doi: 10.1038/s41598-025-05137-3.
The oral administration of insulin offers significant clinical benefits due to its simplicity. This study evaluated piperine's efficacy in improving insulin's intestinal absorption in Wistar rats. Confocal microscopy demonstrated that prolonged retention of insulin-loaded chitosan-coated solid lipid nanoparticles (Ch-In-SLNs) on intestinal mucosa was due to chitosan's mucoadhesive properties. These studies also revealed Ch-In-SLNs permeation in rat intestinal segments. Piperine enhanced the permeation of insulin-loaded nanoparticles, with more particles transported into deeper intestinal layers. The study assessed Ch-In-SLNs with piperine administered orally to diabetic rats. The formulated SLN's effectiveness was evaluated in vivo in overnight-fasted Wistar rats. Male Wistar rats (n = 5) were divided into 8 groups, with the first as diabetic control, and others receiving various treatments, including blank SLN, oral insulin solution (25 IU/kg), subcutaneous (SC) insulin (5 IU/kg), and insulin nanoformulations (25 IU/kg and 50 IU/kg with and without piperine, respectively). Ch-In-SLN with piperine showed a statistically significant reduction (p < 0.05) in blood glucose levels in streptozotocin-induced (STZ) diabetic rats compared to SLNs without piperine and SC insulin. The Ch-In-SLN with piperine formulation demonstrated a noteworthy correlation between pharmacokinetics (PK) and pharmacodynamics (PD). This approach could replace traditional insulin injections and mitigate associated side effects, simplifying insulin therapy.
口服胰岛素因其简便性而具有显著的临床益处。本研究评估了胡椒碱在改善Wistar大鼠肠道对胰岛素吸收方面的功效。共聚焦显微镜显示，负载胰岛素的壳聚糖包被固体脂质纳米粒（Ch-In-SLNs）在肠黏膜上的保留时间延长是由于壳聚糖的黏膜黏附特性。这些研究还揭示了Ch-In-SLNs在大鼠肠段的渗透情况。胡椒碱增强了负载胰岛素纳米粒的渗透，使更多颗粒转运至肠道更深层。该研究评估了口服给予糖尿病大鼠含胡椒碱的Ch-In-SLNs。在禁食过夜的Wistar大鼠体内评估了所制备纳米粒的有效性。将雄性Wistar大鼠（n = 5）分为8组，第一组作为糖尿病对照组，其他组接受各种治疗，包括空白纳米粒、口服胰岛素溶液（25 IU/kg）、皮下注射（SC）胰岛素（5 IU/kg）以及胰岛素纳米制剂（分别含或不含胡椒碱，剂量为25 IU/kg和50 IU/kg）。与不含胡椒碱的纳米粒和皮下注射胰岛素相比，含胡椒碱的Ch-In-SLN使链脲佐菌素诱导（STZ）的糖尿病大鼠血糖水平有统计学意义的降低（p < 0.05）。含胡椒碱的Ch-In-SLN制剂在药代动力学（PK）和药效学（PD）之间显示出显著相关性。这种方法可替代传统胰岛素注射并减轻相关副作用，简化胰岛素治疗。
