Gentiopicroside PLGA Nanospheres: Fabrication, in vitro Characterization, Antimicrobial Action, and in vivo Effect for Enhancing Wound Healing in Diabetic Rats

Purpose: Gentiopicroside (GPS), an adequate bioactive candidate, has a promising approach for enhancing wound healing due to its antioxidant and antimicrobial properties. Its poor aqueous solubility negatively affects oral absorption accompanied by low bioavailability due to intestinal/hepatic first-pass metabolism. Our aim in this study is to fabricate GPS into appropriate nanocarriers (PLGA nanospheres, NSs) to enhance its solubility and hence its oral absorption would be improved. Methods: Normal and ODS silica gel together with Sephadex LH20 column used for isolation of GPS from Gentiana lutea roots. Crude GPS would be further processed for nanospheres fabrication using a single o/w emulsion solvent evaporation technique followed by in vitro optimization study to examine the effect of two formulation variables: polymer (PLGA) and stabilizer (PVA) concentrations on the physical characterizations of prepared NSs. Possible GPS-PLGA chemical and physical interactions have been analyzed using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The optimum GPS-PLGA NSs have been chosen for antimicrobial study to investigate its inhibitory action on Staphylococcus aureus compared with unloaded GPS NSs. Also, a well-designed in vivo study on streptozotocin-induced diabetic rats has been performed to examine the wound healing effect of GPSPLGA NSs followed by histological examination of wound incisions at different day intervals throughout the study. Results: The optimum GPS PLGA NSs (F5) with well-controlled particle size (250.10 +/- 07.86 nm), relative high entrapment efficiency (83.35 +/- 5.71), and the highest % cumulative release (85.79 +/- 8.74) have increased the antimicrobial activity as it exhibited a higher inhibitory effect on bacterial growth than free GPS. F5 showed a greater enhancing impact on wound healing and a significant stimulating effect on the synthesis of collagen fibers compared with free GPS. Conclusion: These findings demonstrate that loading GPS into PLGA NSs is considered a promising strategy ensuring optimum GPS delivery for potential management of wounds.

Automated summary

The study aims to enhance the oral absorption and wound healing effect of gentiopicroside (GPS) by fabricating it into PLGA nanospheres. The optimized GPS-PLGA nanospheres show improved solubility, enhanced antimicrobial activity, and stimulating effect on collagen synthesis. These findings suggest that loading GPS into PLGA nanospheres is a promising strategy for wound management.