International Journal of Nanomedicine (Mar 2022)
Gentiopicroside PLGA Nanospheres: Fabrication, in vitro Characterization, Antimicrobial Action, and in vivo Effect for Enhancing Wound Healing in Diabetic Rats
Abstract
May Almukainzi,1 Thanaa A El-Masry,2 Walaa A Negm,3 Engy Elekhnawy,4 Asmaa Saleh,1,5 Ahmed E Sayed,6 Mohamed A Khattab,7 Dalia H Abdelkader8 1Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 2Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Pharmacognosy Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 4Pharmaceutical Microbiology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 5Department of Biochemistry, Faculty of Pharmacy, Al Azhar University, Cairo, Egypt; 6Faculty of Medicine, Tanta University, Tanta, Egypt; 7Department of Cytology and Histology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; 8Pharmaceutical Technology Department, Faculty of Pharmacy, Tanta University, Tanta, EgyptCorrespondence: Dalia H Abdelkader, Pharmaceutical Technology Department, Faculty of Pharmacy, Tanta University, Tanta, 31111, Egypt, Tel +20 40 3336007, Fax +20 40 3335466, Email [email protected]; [email protected]: 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 GPS-PLGA 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.Keywords: core/shell nanospheres, in-vitro optimization, sustained-release, Staphylococcus aureus, histological evaluation, collagen fibers
