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Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery
Takron Chantadee1, Wichai Santimaleeworagun2, Yaowaruk Phorom3
1Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Abstract:
In recent years, the world has faced the issue of antibiotic resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is a significant problem in various treatments and control of infections. Biocompatible materials with saturated fatty acids of different chain lengths (C8-C18) were studied as matrix formers of localized injectable vancomycin HCl (VCM)-loaded antisolvent-induced in situ forming matrices. The series of fatty acid-based in situ forming matrices showed a low viscosity (5.47-13.97 cPs) and pH value in the range of 5.16-6.78, with high injectability through a 27-G needle (1.55-3.12 N). The preparations exhibited low tolerance to high concentrations of KH2PO4 solution (1.88-5.42% v/v) and depicted an electrical potential change during phase transformation. Their phase transition and matrix formation at the microscopic and macroscopic levels depended on the chain length of fatty acids and solvent characteristics. The VCM release pattern depended on the nucleation/crystallization and solvent exchange behaviors of the delivery system. The 35% w/v of C12-C16 fatty acid-based in situ forming matrix prolonged the VCM release over seven days in which C12, C14, C16 -based formulation reached 56, 84, and 85% cumulative drug release at 7th day. The release data fitted well with Higuchi's model. The developed formulations presented efficient antimicrobial activities against standard S. aureus, MRSA, Escherichia coli, and Candida albicans. Hence, VCM-loaded antisolvent-induced fatty acid-based in situ forming matrix is a potential local delivery system for the treatment of local Gram-positive infection sites, such as joints, eyes, dermis of surgery sites, etc., in the future.
Insights
New fatty acid-based matrices effectively deliver vancomycin HCl (VCM) for treating antibiotic-resistant infections like MRSA. These injectable systems offer sustained VCM release and potent antimicrobial activity against various pathogens.
Area of Science:
- Biomaterials Science
- Pharmaceutical Sciences
- Infectious Diseases
Background:
- Antibiotic resistance, particularly Methicillin-resistant Staphylococcus aureus (MRSA), poses a significant global health challenge.
- Localized infections require effective drug delivery systems to combat resistant pathogens.
- Injectable in situ forming matrices offer potential for sustained drug release at infection sites.
Purpose of the Study:
- To develop and characterize biocompatible, injectable in situ forming matrices for localized delivery of vancomycin HCl (VCM).
- To evaluate the influence of fatty acid chain length on matrix properties, VCM release kinetics, and antimicrobial efficacy.
- To assess the potential of these novel matrices for treating local Gram-positive infections.
Main Methods:
- Synthesis and characterization of fatty acid-based (C8-C18) in situ forming matrices.
- Incorporation of vancomycin HCl (VCM) into the matrices.
- Evaluation of matrix physical properties (viscosity, pH, injectability), phase transformation, VCM release kinetics (Higuchi model), and antimicrobial activity against S. aureus, MRSA, E. coli, and C. albicans.
Main Results:
- Fatty acid-based matrices exhibited low viscosity, suitable pH, and high injectability.
- Matrices demonstrated controlled VCM release over seven days, with C12-C16 formulations showing prolonged release (56-85% cumulative release).
- Formulations displayed significant antimicrobial activity against tested bacterial and fungal strains, including MRSA.
Conclusions:
- Antisolvent-induced, fatty acid-based in situ forming matrices are effective for localized, sustained delivery of vancomycin HCl.
- The developed system shows promise as a potential local delivery strategy for treating Gram-positive infections.
- Further research could explore applications in treating localized infections in joints, eyes, and surgical sites.
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