Tiny Carbopol Nanogels Deliver Metronidazole With Sustained Release and Strong Antimicrobial Punch

Researchers in India have engineered a family of metronidazole-loaded nanogels built on the polymer Carbopol 940, and their systematic comparison of three formulations has identified one clear winner. The study, published in Frontiers in Soft Matter, shows that the amount of polymer used in the formulation dramatically reshapes everything from particle size and swelling behavior to drug release kinetics and antimicrobial potency. The best-performing batch, designated F3, achieved an average particle size of just 143.4 nanometers and released 97.03 percent of its drug payload within eight hours, all while maintaining stable physicochemical properties across 60 days of storage under refrigerated, room-temperature, and accelerated conditions.

The work, led by Sanju Sarkar of BCDA College of Pharmacy & Technology in Kolkata and Bishal Sarkar of Mata Gujri College of Pharmacy in Bihar, addresses a persistent challenge in topical drug delivery. Conventional creams and gels containing metronidazole, a widely used nitroimidazole antimicrobial, often suffer from limited residence time at the application site, uncontrolled drug release, and the need for frequent reapplication. Nanogels offer a compelling alternative because their three-dimensional hydrated polymer networks can entrap drug molecules, control diffusion, and sustain release over extended periods, potentially improving therapeutic outcomes while minimizing systemic side effects.

Metronidazole itself is a well-characterized drug. Classified as a BCS Class I compound with a molecular weight of 171.15 grams per mole and a pKa of approximately 2.6, it is freely soluble in water and exhibits broad activity against obligate anaerobic bacteria and protozoa. Its mechanism of action relies on the intracellular reduction of its nitro group under anaerobic conditions, which generates reactive intermediates that damage microbial DNA and halt nucleic acid synthesis. This makes it a mainstay for treating dermatological, periodontal, gastrointestinal, and gynecological infections caused by anaerobic organisms, but its conventional topical formulations have not always delivered the sustained local concentrations clinicians would prefer.

Carbopol 940, a cross-linked poly(acrylic acid) polymer, was chosen as the nanogel scaffold because of its exceptional swelling capacity, bioadhesivity, biocompatibility, and gelling ability. When hydrated, it forms a three-dimensional network that absorbs water, modulates drug diffusion, and provides rheological properties well suited to topical application. The researchers hypothesized that varying the concentration of this polymer would alter the internal architecture of the gel matrix, and with it, the physicochemical characteristics, swelling behavior, particle size distribution, release kinetics, antimicrobial activity, and stability of the resulting nanogels.

To test this hypothesis, the team prepared three formulations, F1 through F3, using a homogenization-assisted polymer dispersion technique. Each contained 0.02 grams of metronidazole dissolved in propylene glycol, along with glycerol as a humectant and sodium benzoate as a preservative. The key variable was the amount of Carbopol 940: 0.01 grams in F1, 0.015 grams in F2, and 0.02 grams in F3. After dispersing the polymer in distilled water under magnetic stirring and allowing full hydration, the drug solution was added gradually, and the mixture was subjected to high-speed homogenization at 8000 revolutions per minute for one hour. Triethanolamine was then added dropwise to neutralize the formulation to the desired pH, and the nanogels were left overnight at room temperature to reach equilibrium.

Fourier transform infrared spectroscopy confirmed that metronidazole remained chemically compatible with Carbopol 940 throughout the formulation process. The spectra of the loaded nanogels retained the characteristic absorption peaks of both the drug and the polymer without any significant shifts, losses, or new peaks that would indicate chemical interaction or degradation. Peaks corresponding to aromatic C-H rocking vibrations, C-O stretching from the polyacrylic acid structure, and O-H stretching from the hydrated network all appeared as expected, providing strong evidence that the drug was successfully incorporated into the polymer matrix without structural compromise.

All three formulations emerged as homogeneous, smooth, pale yellow gels free of visible lumps, phase separation, and coarse particles. Their pH values ranged from 5.30 to 5.50, comfortably within the physiological range of approximately 4.5 to 6.5 for topical products, minimizing the risk of skin irritation. Drug content uniformity ranged from 94.70 percent in F1 to 99.94 percent in F3, with the higher polymer concentrations apparently enabling better drug entrapment within the hydrated network. Swelling indices followed a similar pattern, with F3 achieving the highest value at 33.00 percent, reflecting favorable interplay between polymer concentration and hydration of the cross-linked matrix.

Rheological testing revealed that all formulations exhibited pseudoplastic, shear-thinning behavior, meaning their viscosity decreased as shear force increased. This property is highly desirable for topical semisolids because it allows the product to flow easily during application yet maintain structural consistency at rest. At low rotational speeds, F1 and F3 showed viscosities of approximately 73,600 and 72,000 centipoise respectively, indicating robust polymer network formation. Dynamic light scattering measurements confirmed that F3 possessed the smallest average particle size at 143.4 nanometers, compared with 484.3 nanometers for F1 and 323.5 nanometers for F2, along with a zeta potential of −12.3 millivolts that suggested moderate electrostatic stability.

In vitro release studies conducted over eight hours using a diffusion cell with phosphate buffer at pH 7.4 revealed a biphasic profile for all three formulations. An initial burst release, attributed to drug molecules adsorbed on or near the surface of the hydrated matrix, was followed by a sustained release phase driven by diffusion through the swollen polymer network. F3 achieved the highest cumulative release of 97.03 percent at the eight-hour mark, outperforming F1 at 95.57 percent and F2 at 92.54 percent. Kinetic modeling showed that the zero-order model best described the release behavior, with F3 yielding the highest coefficient of determination at 0.997, indicating concentration-independent, controlled release. The Korsmeyer-Peppas model suggested anomalous, non-Fickian diffusion involving polymer chain relaxation and swelling effects.

Antimicrobial evaluation using the paper disc diffusion assay against Staphylococcus aureus and Escherichia coli produced strikingly asymmetric results. F3 generated significantly larger and more consistent zones of inhibition against S. aureus than the other formulations, while F1 produced no detectable zones at all under the experimental conditions. No formulation showed significant activity against E. coli, a result consistent with metronidazole’s known spectrum of activity against obligate anaerobes and the natural resistance of aerobic Gram-negative bacteria, whose outer membranes rich in lipopolysaccharides impede drug penetration. The researchers attribute F3’s superior performance against S. aureus to the synergistic effect of its small particle size, high swelling index, and sustained drug release, which together maintained prolonged local metronidazole concentrations near bacterial colonies during the agar diffusion test.

Subject of Research: Development and evaluation of metronidazole-loaded Carbopol 940 nanogels for topical antimicrobial drug delivery

Article Title: Carbopol 940-based metronidazole nanogels: formulation, physicochemical characterization, in vitro drug release, and antimicrobial evaluation

Article References: Sarkar, S., & Sarkar, B. (2026). Carbopol 940-based metronidazole nanogels: formulation, physicochemical characterization, in vitro drug release, and antimicrobial evaluation. Frontiers in Soft Matter, 6, Article 1912568. https://doi.org/10.3389/frsfm.2026.1912568

Image Credits: AI Generated

DOI: 10.3389/frsfm.2026.1912568

Keywords: metronidazole, Carbopol 940, nanogel, topical drug delivery, controlled release, antimicrobial activity, drug release kinetics, Staphylococcus aureus, polymeric network, pharmaceutical formulation, stability study, rheology