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

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.

Materials and methods

Manufacturing berberine-loaded chitosan/SLN nanoparticles

Berberine-loaded chitosan/SLN nanoformulation was prepared using a previously described solvent-injection method followed by a high-pressure homogenization process. Briefly, berberine (50 mg) and the solid lipid Witepsol 85E (40 mg) were dissolved at 75 °C in 1 mL of a mixed solution (acetone and ethanol in an equal ratio (1:1 v/v)) until a homogenous dispersion appeared. To construct berberine-loaded chitosan-coated SLN nanoparticles, prepared solid lipid/berberine mix was injected into hot double-distilled water (75 °C) containing chitosan (0.5 mg/mL) and a stabilizing surfactant (Pluronic, 2.5 mg/mL). The prepared solution was emulsified by high agitation (25,000 rpm for 4 min at 70 °C) and then homogenized at the same temperature through employing nine homogenization cycles at 750 bars by a high-pressure homogenizer. Immediately after homogenization, the obtained suspension was cooled in an ice-water bath to keep the structure of berberine-loaded chitosan/SLN nanoparticles stable. Finally, the prepared nanoformulation was filtered by a 400 nm filter and then freeze-dried.

Liu Y, Hussain SA, Yue H. Protective effects of berberine-loaded chitosan/solid lipid nanoparticles in streptozotocin-induced gestational diabetes mellitus rats. Exp Biol Med (Maywood). 2025 Dec 12;250:10749. doi: 10.3389/ebm.2025.10749. PMID: 41488874; PMCID: PMC12757692.

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