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Using Fickian diffusion principles within an ANSYS-CFX computational fluid dynamic model, we validated the model against our <jats:italic>in vitro<\/jats:italic> vancomycin release and agar diffusion studies, as well as previously published <jats:italic>in vivo<\/jats:italic> data, confirming the reliability of the model. The model predictions demonstrated the effectiveness of the system in inhibiting bacterial growth in surrounding tissue with no observed toxicity, with a peak vancomycin concentration of 0.95 mg\/ml at 6 hours, followed by a decrease to levels that remained effective for antibacterial activity. Furthermore, a sensitivity analysis revealed that the model is particularly sensitive to the half-life of vancomycin, with a maximum sensitivity index of 0.8, indicating its greater impact on the prediction accuracy than the diffusion coefficient, which has a maximum sensitivity index of 0.5. Therefore, precise input of vancomycin\u2019s half-life is critical for accurate predictions. These findings offer substantial support for the efficacy of the local delivery system as a promising therapeutic approach against implant-associated infections.<\/jats:p>","DOI":"10.1371\/journal.pone.0311521","type":"journal-article","created":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T17:23:58Z","timestamp":1730481838000},"page":"e0311521","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mathematical modeling of vancomycin release from Poly-L-Lactic Acid-Coated implants"],"prefix":"10.1371","volume":"19","author":[{"given":"Papon","family":"Thamvasupong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-4526","authenticated-orcid":true,"given":"Kwanchanok","family":"Viravaidya-Pasuwat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,11,1]]},"reference":[{"key":"pone.0311521.ref001","doi-asserted-by":"crossref","first-page":"113973","DOI":"10.1016\/j.addr.2021.113973","article-title":"Challenges and solutions in polymer drug delivery for bacterial biofilm treatment: A tissue-by-tissue account","volume":"178","author":"K Kasza","year":"2021","journal-title":"Adv Drug Deliv Rev"},{"key":"pone.0311521.ref002","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jconrel.2020.12.025","article-title":"Local drug delivery systems for inflammatory diseases: Status quo, challenges, and opportunities","volume":"330","author":"YC Chen","year":"2021","journal-title":"J Contr Release"},{"key":"pone.0311521.ref003","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.addr.2017.09.015","article-title":"Nanoparticle-based local antimicrobial drug delivery","volume":"127","author":"W Gao","year":"2018","journal-title":"Adv Drug Deliv Rev"},{"issue":"8","key":"pone.0311521.ref004","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.3390\/polym14081611","article-title":"Polymeric Coatings and Antimicrobial Peptides as Efficient Systems for Treating Implantable Medical Devices Associated-Infections","volume":"14","author":"I Negut","year":"2022","journal-title":"Polymers"},{"issue":"12","key":"pone.0311521.ref005","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1007\/s10853-021-05776-7","article-title":"Polymeric approach to combat drug-resistant methicillin-resistant Staphylococcus aureus","volume":"56","author":"S Kanth","year":"2021","journal-title":"J Mater Sci"},{"key":"pone.0311521.ref006","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.3390\/ijms20112747","article-title":"Antimicrobial Polymers: The Potential Replacement of Existing Antibiotics?","volume":"20","author":"N Kamaruzzaman","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"17","key":"pone.0311521.ref007","doi-asserted-by":"crossref","DOI":"10.3390\/polym14173493","article-title":"Controlled Release Mechanism of Vancomycin from Double-Layer Poly-L-Lactic Acid-Coated Implants for Prevention of Bacterial Infection","volume":"14","author":"P Thamvasupong","year":"2022","journal-title":"Polymers"},{"key":"pone.0311521.ref008","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3389\/fphar.2014.00174","article-title":"Implementation of pharmacokinetic and pharmacodynamic strategies in early research phases of drug discovery and development at Novartis Institute of Biomedical Research","volume":"5","author":"T Tuntland","year":"2014","journal-title":"Front Pharmacol"},{"issue":"7","key":"pone.0311521.ref009","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacbts.2019.10.008","article-title":"Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Is it Time to Rethink Our Current Approach?","volume":"4","author":"GA Van Norman","year":"2019","journal-title":"JACC Basic Transl Sci"},{"issue":"4","key":"pone.0311521.ref010","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3390\/sci3040045","article-title":"Replacement Strategies for Animal Studies in Inhalation Testing","volume":"3","author":"E. 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