Metronidazole delivery from electrospun poly(methyl methacrylate) (PMMA) nanofibers was investigated, the effect and relationship between fiber diameter and drug-release kinetics was clarified. PMMA solutions (4, 6 and 8 wt% in DMF) containing 5 wt% metronidazole was electrospun to produce three different morphologies (Fine, Medium, Thick) which means fiber diameters of 209 ± 18, 532 ± 66 and 685 ± 61 nm, respectively. Physical properties of web and its composition were characterized by SEM, FE-SEM/EDX mapping and XRD. SEM confirmed cylindrical fibers for 4–6 wt% PMMA and ribbon fibers at higher concentrations; EDX mapping revealed Nitrogen element at 3.47 wt%, uniformly distributed in the fibers, indicating homogeneous incorporation of metronidazole. XRD patterns exhibited a broad amorphous halo (2θ ≈ 10–25°), indicating an amorphous PMMA polymeric matrix. In vitro release in PBS (pH 7.4), monitored by UV–Vis spectroscopy over 288 h, showed a negligible initial burst (< 1%) and a clear dependence on fiber diameter: cumulative release at 288 h was 94.7%, 86.3% and 73.4% for the Fine, Medium and Thick samples, respectively. Kinetic analysis indicated that all samples were best described by a first-order, diffusion-controlled release model, with apparent rate constants: fine sample (K1 = 0.0097 h−1), medium and thick samples (K1 = 0.0075 and 0.0048 h−1). A strong empirical correlation between the kinetic constant and fiber diameter (linear fit, R2 = 0.9328) was found and is consistent with the mechanistic relation <InlineEquation ID="IEq1"> <EquationSource Format="TEX">$K \propto \frac{1}{d}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>K</mi> <mo>∝</mo> <mfrac> <mn>1</mn> <mi>d</mi> </mfrac> </mrow> </math></EquationSource> </InlineEquation> derived from a cylindrical mass-transfer model in dilute media. These results demonstrate that fiber diameter is an effective design parameter to tune metronidazole release from PMMA nanofibers and that release rates can be predicted from fiber geometry under the conditions studied. Graphical Abstract

Relating the Drug Release Kinetic Constant to Nanofiber Diameter: Tuning Metronidazole Release from PMMA Nanofibrous Web

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发表日期：

2026年4月8日

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Hanieh Saghafi,
Mohammad Amani Tehran,
Reza Mohammad Ali Malek

摘要

Metronidazole delivery from electrospun poly(methyl methacrylate) (PMMA) nanofibers was investigated, the effect and relationship between fiber diameter and drug-release kinetics was clarified. PMMA solutions (4, 6 and 8 wt% in DMF) containing 5 wt% metronidazole was electrospun to produce three different morphologies (Fine, Medium, Thick) which means fiber diameters of 209 ± 18, 532 ± 66 and 685 ± 61 nm, respectively. Physical properties of web and its composition were characterized by SEM, FE-SEM/EDX mapping and XRD. SEM confirmed cylindrical fibers for 4–6 wt% PMMA and ribbon fibers at higher concentrations; EDX mapping revealed Nitrogen element at 3.47 wt%, uniformly distributed in the fibers, indicating homogeneous incorporation of metronidazole. XRD patterns exhibited a broad amorphous halo (2θ ≈ 10–25°), indicating an amorphous PMMA polymeric matrix. In vitro release in PBS (pH 7.4), monitored by UV–Vis spectroscopy over 288 h, showed a negligible initial burst (< 1%) and a clear dependence on fiber diameter: cumulative release at 288 h was 94.7%, 86.3% and 73.4% for the Fine, Medium and Thick samples, respectively. Kinetic analysis indicated that all samples were best described by a first-order, diffusion-controlled release model, with apparent rate constants: fine sample (K₁ = 0.0097 h⁻¹), medium and thick samples (K₁ = 0.0075 and 0.0048 h⁻¹). A strong empirical correlation between the kinetic constant and fiber diameter (linear fit, R² = 0.9328) was found and is consistent with the mechanistic relation $K \propto \frac{1}{d}$ $K \propto \frac{1}{d}$ derived from a cylindrical mass-transfer model in dilute media. These results demonstrate that fiber diameter is an effective design parameter to tune metronidazole release from PMMA nanofibers and that release rates can be predicted from fiber geometry under the conditions studied.

Graphical Abstract