Vancomycin-Loaded Nano Bovine Hydroxyapatite-Poly(lactic-co-glycolic acid)-Polyethylene Glycol Nanofibers for Controlled Drug Delivery: Design, Characterization, and Kinetic Modeling
Keywords:
Electrospinning, Implant, Nanofiber, Osteomyelitis, Vancomycin
Abstract
Bone fractures and orthopedic surgical interventions are associated with an increased risk of osteomyelitis, necessitating effective antibiotic therapy. However, systemic antibiotic administration is often limited by poor drug penetration due to tissue devascularization at the fracture site and the formation of bacterial biofilms, which further contribute to antimicrobial resistance and systemic toxicity. Consequently, localized drug delivery systems have emerged as a promising strategy to overcome these limitations. This study aimed to fabricate vancomycin (VAN)-loaded nanofiber implants based on a nano bovine hydroxyapatite (NBHA)–poly(lactic-co-glycolic acid) (PLGA)–polyethylene glycol (PEG) matrix with optimized physicochemical properties and a sustained release profile over 28 days. The nanofibers were fabricated via electrospinning using an optimized formulation derived from a prior Design of Experiments (DoE) study. The resulting nanofibers exhibited uniform morphology, with an average fiber diameter of 91.42± 0.85 nm and a tensile strength of 2.152±0.289 MPa, indicating suitable mechanical properties. In vitro release studies demonstrated a sustained release profile with a dissolution efficiency of 67.74% over 28 days. The release kinetics were best described by the Peppas–Sahlin model during the initial phase and transitioned to the Higuchi model at later stages, suggesting a combination of diffusion- and polymer relaxation-controlled mechanisms. Overall, VAN-loaded NBHA–PLGA–PEG nanofiber implants demonstrate significant potential as a localized and controlled drug delivery platform for osteomyelitis therapy while concurrently supporting bone regeneration.
References
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21. Khatib, M. El, Mauro, A., Di Mattia, M., Wyrwa, R., Schweder, M., Ancora, M., Lazzaro, F., Berardinelli, P., Valbonetti, L., Di Giacinto, O., Polci, A., Cammà, C., Schnabelrauch, M., Barboni, B., & Russo, V. (2020). Electrospun PLGA fiber diameter and alignment of tendon biomimetic fleece potentiate tenogenic differentiation and immunomodulatory function of amniotic epithelial stem cells. Cells, 9(5), 1–26. https://doi.org/10.3390/cells9051207
22. Leonardi, D., Barrera, M. G., Lamas, M. C., & Salomón, C. J. (2007). Development of prednisone: Polyethylene glycol 6000 fast-release tablets from solid dispersions: Solid-state characterization, dissolution behavior, and formulation parameters. AAPS PharmSciTech, 8(4). https://doi.org/10.1208/pt0804108
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29. Rani, K. C., Imanto, T., Primaharinastiti, R., Hariyadi, D. M., & Hendradi, E. (2019). The effect of composite composition ratio on the physicochemical characteristics of bovine hydroxyapatite-chitosan-ciprofloxacin implant. Proceedings of the Pakistan Academy of Sciences: Part B, 56(4).
30. Rujitanapanich, S., Kumpapan, P., & Wanjanoi, P. (2014). Synthesis of hydroxyapatite from oyster shell via precipitation. Energy Procedia, 56(C), 112–117. https://doi.org/10.1016/j.egypro.2014.07.138
31. Sarwar, H., Martin, R. A., Coleman, H. M., & Courtenay, A. (2025). Antibiotic-Loaded Bioglass 45S5 for the Treatment and Prevention of Staphylococcus aureus Infections in Orthopaedic Surgery : A Novel Strategy Against Antimicrobial Resistance. 1–25.
32. Serri, A., Moghimi, H. R., Mahboubi, A., & Zarghi, A. (2017). Stability-indicating HPLC method for determination of vancomycin hydrochloride in the pharmaceutical dosage forms. Acta Poloniae Pharmaceutica - Drug Research, 74(1), 73–79.
33. Shi, C., Ye, J., Xu, R., Jin, W., Xu, S., Teng, F., & Lin, N. (2021). Effect of the vancomycin minimum inhibitory concentration on clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus bacteraemia: A systematic review and meta-analysis. BMJ Open, 11(1), 1–10. https://doi.org/10.1136/bmjopen-2020-040675
34. Sulistyani, M. (2018). Spektroskopi Fourier Transform Infra Red Metode Reflektansi (Atr-Ftir) Pada Optimasi Pengukuran Spektrum Vibrasi Vitamin C. Jurnal TEMAPELA, 1(2), 39–43. https://doi.org/10.25077/temapela.1.2.39-43.2018
35. Sun, H., Liu, C., Li, X., Liu, H., Zhang, W., Yang, H., Li, C., & Yang, L. (2020). A novel calcium phosphate–based nanocomposite for the augmentation of cement-injectable cannulated pedicle screws fixation: A cadaver and biomechanical study. Journal of Orthopaedic Translation, 20, 56–66. https://doi.org/https://doi.org/10.1016/j.jot.2019.08.001
36. Sun, H. W., Zhang, H., Zhen, Q., Wang, S. F., Hu, J. J., Cui, J. Q., & Qian, X. M. (2022). Large-scale preparation of polylactic acid/polyethylene glycol micro/nanofiber fabrics with aligned fibers via a post-drafting melt blown process. Journal of Polymer Research, 29(8). https://doi.org/10.1007/s10965-022-03184-2
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2. Aisah, N., Effendi, M. D., Setiawan, J., Tenaga, B., & Nasional, N. (2019). Synthesis and Characterizations of Hydroxyapatite from Bovine Bone Using Alkaline Hydrolysis Method. April 2018. https://doi.org/10.23960/ins.v3i1.124
3. Ajalloueian, F., Tavanai, H., Hilborn, J., Donzel-Gargand, O., Leifer, K., Wickham, A., & Arpanaei, A. (2014). Emulsion electrospinning as an approach to Fabricate PLGA/chitosan nanofibers for biomedical applications. BioMed Research International, 2014. https://doi.org/10.1155/2014/475280
4. Aldabib, J. M., & Ishak, Z. A. M. (2020). Effect of hydroxyapatite filler concentration on mechanical properties of poly (methyl methacrylate) denture base. SN Applied Sciences, 2(4), 1–14. https://doi.org/10.1007/s42452-020-2546-1
5. Alegrete, N., Sousa, S. R., Padrão, T., Carvalho, Â., Lucas, R., Canadas, R. F., Lavrador, C., Alexandre, N., Gärtner, F., Monteiro, F. J., & Gutierres, M. (2023). Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model. Bioengineering, 10(2), 1–19. https://doi.org/10.3390/bioengineering10020206
6. Alshaikh, R. A., Chullipalliyalil, K., Waeber, C., & Ryan, K. B. (2024). Extended siponimod release via low-porosity PLGA fibres: a comprehensive three-month in vitro evaluation for neovascular ocular diseases. Biomaterials Science, 12(18), 4823–4844. https://doi.org/10.1039/d4bm00339j
7. Badaraev, A. D., Tran, T. H., Drozd, A. G., Plotnikov, E. V., Dubinenko, G. E., Kozelskaya, A. I., Rutkowski, S., & Tverdokhlebov, S. I. (2023). Effect of PLGA Concentration in Electrospinning Solution on Biocompatibility, Morphology and Mechanical Properties of Nonwoven Scaffolds. Technologies, 11(5). https://doi.org/10.3390/technologies11050137
8. Cao, Z., Jiang, D., Yan, L., & Wu, J. (2016). In vitro and in vivo osteogenic activity of the novel vancomycin-loaded bone-like hydroxyapatite / poly ( amino acid ) scaffold. 30(1), 1566–1577. https://doi.org/10.1177/0885328215623735
9. CeCe, R., Jining, L., Islam, M., Korvink, J. G., & Sharma, B. (2024). An Overview of the Electrospinning of Polymeric Nanofibers for Biomedical Applications Related to Drug Delivery. Advanced Engineering Materials, 26(1). https://doi.org/10.1002/adem.202301297
10. Fathi, H. A., Abdelkader, A., AbdelKarim, M. S., Abdelaziz, A. A., El Mokhtar, M. A., Allam, A., Fetih, G., El Badry, M., & Elsabahy, M. (2020). Electrospun vancomycin-loaded nanofibers for management of methicillin-resistant Staphylococcus aureus-induced skin infections. International Journal of Pharmaceutics, 586(July), 119620. https://doi.org/10.1016/j.ijpharm.2020.119620
11. Fathi, M., Akbari, B., & Taheriazam, A. (2019). Antibiotics drug release controlling and osteoblast adhesion from Titania nanotubes arrays using silk fibroin coating. Materials Science & Engineering. C, Materials for Biological Applications, 103(December 2018), 109743. https://doi.org/10.1016/j.msec.2019.109743
12. Fathi, M., Akbari, B., Taheriazam, A., & Sodagar, A. (2022). Surface functionalization of Titania Nanotubes arrays and vancomycin controlled release using Silk Fibroin Nanofibers coating. Journal of Drug Delivery Science and Technology, 71(April), 103320. https://doi.org/https://doi.org/10.1016/j.jddst.2022.103320
13. Gama e Silva, G. L., Sato de Souza Bustamante Monteiro, M., dos Santos Matos, A. P., Santos-Oliveira, R., Kenechukwu, F. C., & Ricci-Júnior, E. (2022). Nanofibers in the treatment of osteomyelitis and bone regeneration. Journal of Drug Delivery Science and Technology, 67(November 2021), 102999. https://doi.org/10.1016/j.jddst.2021.102999
14. Gentile, P., Chiono, V., Carmagnola, I., & Hatton, P. V. (2014). An Overview of Poly ( lactic- co -glycolic ) Acid ( PLGA ) -Based Biomaterials for Bone Tissue Engineering. 3640–3659. https://doi.org/10.3390/ijms15033640
15. Haider, A., Gupta, K. C., & Kang, I. K. (2014). PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration. Nanoscale Research Letters, 9(1), 1–12. https://doi.org/10.1186/1556-276X-9-314
16. Imanto, T., Sambudi, N. S., Zai, K., Nanda, T., & Sulaiman, S. (2024). Advances in Antibiotic-Loaded Nanofibers for the Treatment of Bone Infections : 21(2), 161–175. https://doi.org/10.23917/pharmacon.v21i2.6986
17. Imanto, T., Sambudi, N. S., Zai, K., Nanda, T., & Sulaiman, S. (2025). Optimizing Temperature and Time in Bovine Bone Extraction : A Novel approach to Enhanced Hydroxyapatite Production for Advanced Bone Tissue Engineering Applications. 18(September), 4158–4166. https://doi.org/10.52711/0974-360X.2025.00598
18. Ito, T., Ohbuchi, A., Nakano, K., Sasai, T., & Xue, Z. (2019). Simple measurement of the major elemental composition with SEM-EDX and its application to a geological survey. Bunseki Kagaku, 68(6), 373–380. https://doi.org/10.2116/bunsekikagaku.68.373
19. Jiang, N., Wang, B., Chai, Y., Wu, X., Tang, P., Zhang, Y., & Yu, B. (2019). Chinese expert consensus on diagnosis and treatment of infection after fracture fixation. Injury, 50(11), 1952–1958. https://doi.org/https://doi.org/10.1016/j.injury.2019.08.002
20. Keshavarzi, F., Nadaraja, V., Alias, A., & Farrukh, M. J. (2022). Evaluation of Trough-Based Vancomycin Therapy in Achieving Targeted Area Under the Curve in Haemodialysis Cases. 33(3), 484–492.
21. Khatib, M. El, Mauro, A., Di Mattia, M., Wyrwa, R., Schweder, M., Ancora, M., Lazzaro, F., Berardinelli, P., Valbonetti, L., Di Giacinto, O., Polci, A., Cammà, C., Schnabelrauch, M., Barboni, B., & Russo, V. (2020). Electrospun PLGA fiber diameter and alignment of tendon biomimetic fleece potentiate tenogenic differentiation and immunomodulatory function of amniotic epithelial stem cells. Cells, 9(5), 1–26. https://doi.org/10.3390/cells9051207
22. Leonardi, D., Barrera, M. G., Lamas, M. C., & Salomón, C. J. (2007). Development of prednisone: Polyethylene glycol 6000 fast-release tablets from solid dispersions: Solid-state characterization, dissolution behavior, and formulation parameters. AAPS PharmSciTech, 8(4). https://doi.org/10.1208/pt0804108
23. Li, J. J. Y., Jian, T. F., & Li, Z. X. (2012). Vancomycin-loaded nano-hydroxyapatite pellets to treat MRSA-induced chronic osteomyelitis with bone defect in rabbits. 207–215. https://doi.org/10.1007/s00011-011-0402-x
24. Makadia, H. K., & Siegel, S. J. (2011). Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymers, 3(3), 1377–1397. https://doi.org/10.3390/polym3031377
25. Mills, H., Donnelly, L., & Platt, S. (2024). Locally Delivered Antibiotics in Fracture-Related Infection. Cureus, 16(11). https://doi.org/10.7759/cureus.73210
26. Pereira, E. D., Cerruti, R., Fernandes, E., Peña, L., Saez, V., Pinto, J. C., Ramón, J. A., Oliveira, G. E., & De Souza, F. G. (2016). Influence of PLGA and PLGA-PEG on the dissolution profile of oxaliplatin. Polimeros, 26(2), 137–143. https://doi.org/10.1590/0104-1428.2323
27. Persano, L., Camposeo, A., Tekmen, C., & Pisignano, D. (2013). Industrial upscaling of electrospinning and applications of polymer nanofibers: A review. Macromolecular Materials and Engineering, 298(5), 504–520. https://doi.org/10.1002/mame.201200290
28. Pirmoradian, A., Behshad, Y., Sharifi, F., Alipour, S., Jiang, L., & Sabzi, M. (2023). Development of Antibiotic Releasing Electrospun Nanofibrous Mats Based on Gelatin. Materials Chemistry Horizons, 2023(3), 185–193.
29. Rani, K. C., Imanto, T., Primaharinastiti, R., Hariyadi, D. M., & Hendradi, E. (2019). The effect of composite composition ratio on the physicochemical characteristics of bovine hydroxyapatite-chitosan-ciprofloxacin implant. Proceedings of the Pakistan Academy of Sciences: Part B, 56(4).
30. Rujitanapanich, S., Kumpapan, P., & Wanjanoi, P. (2014). Synthesis of hydroxyapatite from oyster shell via precipitation. Energy Procedia, 56(C), 112–117. https://doi.org/10.1016/j.egypro.2014.07.138
31. Sarwar, H., Martin, R. A., Coleman, H. M., & Courtenay, A. (2025). Antibiotic-Loaded Bioglass 45S5 for the Treatment and Prevention of Staphylococcus aureus Infections in Orthopaedic Surgery : A Novel Strategy Against Antimicrobial Resistance. 1–25.
32. Serri, A., Moghimi, H. R., Mahboubi, A., & Zarghi, A. (2017). Stability-indicating HPLC method for determination of vancomycin hydrochloride in the pharmaceutical dosage forms. Acta Poloniae Pharmaceutica - Drug Research, 74(1), 73–79.
33. Shi, C., Ye, J., Xu, R., Jin, W., Xu, S., Teng, F., & Lin, N. (2021). Effect of the vancomycin minimum inhibitory concentration on clinical outcomes in patients with methicillin-susceptible Staphylococcus aureus bacteraemia: A systematic review and meta-analysis. BMJ Open, 11(1), 1–10. https://doi.org/10.1136/bmjopen-2020-040675
34. Sulistyani, M. (2018). Spektroskopi Fourier Transform Infra Red Metode Reflektansi (Atr-Ftir) Pada Optimasi Pengukuran Spektrum Vibrasi Vitamin C. Jurnal TEMAPELA, 1(2), 39–43. https://doi.org/10.25077/temapela.1.2.39-43.2018
35. Sun, H., Liu, C., Li, X., Liu, H., Zhang, W., Yang, H., Li, C., & Yang, L. (2020). A novel calcium phosphate–based nanocomposite for the augmentation of cement-injectable cannulated pedicle screws fixation: A cadaver and biomechanical study. Journal of Orthopaedic Translation, 20, 56–66. https://doi.org/https://doi.org/10.1016/j.jot.2019.08.001
36. Sun, H. W., Zhang, H., Zhen, Q., Wang, S. F., Hu, J. J., Cui, J. Q., & Qian, X. M. (2022). Large-scale preparation of polylactic acid/polyethylene glycol micro/nanofiber fabrics with aligned fibers via a post-drafting melt blown process. Journal of Polymer Research, 29(8). https://doi.org/10.1007/s10965-022-03184-2
37. Tao, F., Ma, S., Tao, H., Jin, L., Luo, Y., Zheng, J., Xiang, W., & Deng, H. (2021). Chitosan-based drug delivery systems: From synthesis strategy to osteomyelitis treatment - A review. Carbohydrate Polymers, 251, 117063. https://doi.org/10.1016/j.carbpol.2020.117063
38. Unagolla, J. M., & Jayasuriya, A. C. (2018). Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system. European Journal of Pharmaceutical Sciences, 114(December 2017), 199–209. https://doi.org/10.1016/j.ejps.2017.12.012
39. Yang, J., Zeng, H., Luo, Y., Chen, Y., Wang, M., Wu, C., & Hu, P. (2024). Recent Applications of PLGA in Drug Delivery Systems. Polymers, 16(18), 1–25. https://doi.org/10.3390/polym16182606
40. Zapata, M. E. V., Tovar, C. D. G., & Hernandez, J. H. M. (2020). The Role of Chitosan and Graphene Oxide in Bioactive and Antibacterial Properties of Acrylic Bone Cements. Biomolecules, 10(12). https://doi.org/10.3390/biom10121616
41. Zhang, L., Yan, J., Yin, Z., Tang, C., Guo, Y., Li, D., Wei, B., Xu, Y., Gu, Q., & Wang, L. (2014). Electrospun vancomycin-loaded coating on titanium implants for the prevention of implant-associated infections. International Journal of Nanomedicine, 9(1), 3027–3036. https://doi.org/10.2147/IJN.S63991
Published
2026-05-06
How to Cite
Teguh Imanto, Nonni Soraya Sambudi, Khadijah Zai, & Teuku Nanda Saifullah Sulaiman. (2026). Vancomycin-Loaded Nano Bovine Hydroxyapatite-Poly(lactic-co-glycolic acid)-Polyethylene Glycol Nanofibers for Controlled Drug Delivery: Design, Characterization, and Kinetic Modeling. Indonesian Journal of Pharmacy, 37(2), 430–440. https://doi.org/10.22146/ijp.29578
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Research Article
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