# Protective effects of berberine-loaded chitosan/solid lipid nanoparticles in streptozotocin-induced gestational diabetes mellitus rats

## TL;DR

This study shows that encapsulating berberine in chitosan-coated nanoparticles improves its effectiveness in treating gestational diabetes in rats.

## Contribution

The novel contribution is the development of chitosan-coated solid lipid nanoparticles to enhance berberine's bioavailability and therapeutic effects in gestational diabetes.

## Key findings

- Berberine-loaded nanoparticles significantly improved glycemic indices and antioxidant balance in GDM rats.
- Nanoparticle formulation provided higher oral bioavailability and sustained release of berberine compared to free berberine.
- Chitosan-coated SLNs showed high stability, encapsulation efficiency, and therapeutic impact in STZ-induced GDM models.

## Abstract

Berberine, known as an antioxidant agent, can improve glycemic indices in animal models of diabetes; however, it is clinically limited by poor bioavailability. Nanoparticles show the desirable capacity as delivery platforms for improving the bioavailability of medicinal agents. Here, we aimed to enhance the bioavailability and therapeutic impacts of berberine in streptozotocin (STZ)-induced gestational diabetes mellitus (GDM) rats by its encapsulation into the chitosan-coated solid lipid nanoparticles (SLNs) formulation. Berberine-loaded chitosan/SLN nanoparticles were formulated by the solvent-injection approach followed by a homogenization operation. The particle size, surface charge, and polydispersity index, as well as encapsulation efficiency percent (EE%), in vitro stability and berberine release, and in vivo pharmacokinetics were studied. Glycemic indices, such as fasting glucose and insulin, oral glucose tolerance, insulin tolerance, and homeostasis model of insulin resistance (HOMA-IR) scores, as well as the activity level of liver antioxidant and pro-oxidant enzymes, were evaluated in STZ-induced GDM rats. The particle size of berberine-loaded chitosan/SLN formulation was detected in the nano-range with high stability and high EE% as well as a sustained-release profile. Berberine nanoparticle treatment could provide a significantly higher oral bioavailability of berberine in experimental rats. Berberine nanoparticles remarkably reversed the altered glycemic indices, body weight, and pro-oxidant/antioxidant balance in STZ-induced GDM rats, with significantly higher effects than free berberine. In conclusion, chitosan-coated SLN nanoparticles firmly enhanced the therapeutic impacts of berberine on STZ-induced GDM, suggesting chitosan-coated SLN nanoparticles as an efficient oral delivery system for enhancing the bioavailability of berberine and, thus, improving its pharmacological impacts.

Preparation and evaluation process of berberine-loaded chitosan/solid lipid nanoparticles. Includes molecular structures, an in vivo study depiction with a rat, and various bar graphs showing the concentration and activity levels of different enzymes and indices such as NO, MDA, MPO, and glutathione, along with fasting blood glucose and plasma insulin levels across different treatment groups. Statistical significance values are indicated.