Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats

Abstract 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 so...

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Main Authors: Indu Raghunath, Marina Koland, Suprit D. Saoji, Sarad Pawar Naik Bukke, N. Shridhar Deshpande, Varsha Augustin, Nilesh Rarokar, Chandrashekar Thalluri
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05137-3
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author Indu Raghunath
Marina Koland
Suprit D. Saoji
Sarad Pawar Naik Bukke
N. Shridhar Deshpande
Varsha Augustin
Nilesh Rarokar
Chandrashekar Thalluri
author_facet Indu Raghunath
Marina Koland
Suprit D. Saoji
Sarad Pawar Naik Bukke
N. Shridhar Deshpande
Varsha Augustin
Nilesh Rarokar
Chandrashekar Thalluri
author_sort Indu Raghunath
collection DOAJ
description Abstract 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.
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spelling doaj-art-9a4c1b9328a24cac92d01e5bb04ccbe82025-08-20T03:03:40ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-05137-3Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in ratsIndu Raghunath0Marina Koland1Suprit D. Saoji2Sarad Pawar Naik Bukke3N. Shridhar Deshpande4Varsha Augustin5Nilesh Rarokar6Chandrashekar Thalluri7Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University)Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University)Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur UniversityDepartment of Pharmaceutics and Pharmaceutical Technology, Kampala International UniversityDepartment of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University) NGSM Institute of Pharmaceutical Sciences, NUCARE, Nitte (Deemed to be University)Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Faculty of Pharmaceutical Science, Assam down town University (AdtU)Abstract 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.https://doi.org/10.1038/s41598-025-05137-3StreptozotocinWistar ratsInsulinSolid lipid nanoparticlesIn vivoDiabetes
spellingShingle Indu Raghunath
Marina Koland
Suprit D. Saoji
Sarad Pawar Naik Bukke
N. Shridhar Deshpande
Varsha Augustin
Nilesh Rarokar
Chandrashekar Thalluri
Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats
Scientific Reports
Streptozotocin
Wistar rats
Insulin
Solid lipid nanoparticles
In vivo
Diabetes
title Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats
title_full Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats
title_fullStr Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats
title_full_unstemmed Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats
title_short Effects of piperine on intestinal permeation, pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats
title_sort effects of piperine on intestinal permeation pharmacodynamics and pharmacokinetics of insulin loaded chitosan coated solid lipid nanoparticles in rats
topic Streptozotocin
Wistar rats
Insulin
Solid lipid nanoparticles
In vivo
Diabetes
url https://doi.org/10.1038/s41598-025-05137-3
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