Design and Optimization of Colon-Targeted Multiparticulate Nanosponges of Metronidazole for Enhanced Release and Stability
Shubhangi B Khade*, Raosaheb S Shendge
Department of Pharmaceutics, Sanjivani College of Pharmaceutical Education and Research, Savitribai Phule Pune University, Sahajanand Nagar, Shingnapur, Kopargaon, Ahmednagar, Maharashtra-423603, India
Received: 16th Jun, 2025; Revised: 20th Jul, 2025; Accepted: 29th Jul, 2025; Available Online: 25th Sep, 2025
ABSTRACT
This work sought to formulate and optimize Metronidazole-loaded nanosponges to improve solubility, entrapment efficiency, and sustained release. Nanosponges were synthesized by the emulsion solvent evaporation technique and optimized utilizing a central composite design. Among 20 formulations, batch F9 demonstrated excellent results with a mean particle size of 200.78 nm, a zeta potential of −31.7 mV, and a polydispersity index of 0.205, signifying a uniform nanosized dispersion. The entrapment efficiency varied between 81.55% and 85.95%, with formulation F9 exhibiting the greatest efficiency at 85.95 ± 0.95% and a drug loading capacity of 79.53 ± 0.13%. In-vitro release tests indicated sustained drug release, with F9 attaining 95.15 ± 1.20% release within 12 hours, adhering to zero-order kinetics (R² = 0.9973) and a Higuchi diffusion-controlled mechanism (R² = 0.9217). Capsule formulation of the optimized batch showed consistent drug content (99.15 ± 0.02%) and stability over 90 days without significant changes in release profile (94.10 ± 0.01% at 3 months). These findings suggest that nanosponge-based delivery of Metronidazole offers improved solubility, entrapment, and sustained release with good stability, making it a promising approach for effective oral drug delivery.
Keywords: Metronidazole; Nanosponges; Central Composite Design; Entrapment Efficiency; Sustained Release; Drug Stability
How to cite this article: Shubhangi B Khade, Raosaheb S Shendge. Design and Optimization of Colon-Targeted Multiparticulate Nanosponges of Metronidazole for Enhanced Release and Stability. International Journal of Drug Delivery Technology. 2025;15(3):1187-97. doi: 10.25258/ijddt.15.3.38
REFERENCES
- Hakim LK, Yazdanian M, Alam M, Abbasi K, Tebyaniyan H, Tahmasebi E, et al. Biocompatible and Biomaterials Application in Drug Delivery System in Oral Cavity. Evid Based Complement Alternat Med. 2021;2021:9011226.
- Ouyang J, Zhang Z, Deng B, Liu J, Wang L, Liu H, et al. Oral Drug Delivery Platforms for Biomedical Applications. Mater Today. 2023;62:296–326.
- He H, Lu Y, Qi J, Zhu Q, Chen Z, Wu W. Adapting Liposomes for Oral Drug Delivery. Acta Pharm Sin B. 2019;9(1):36–48.
- Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in Oral Drug Delivery. Front Pharmacol. 2021;12:618411.
- Lou J, Duan H, Qin Q, Teng Z, Gan F, Zhou X, Zhou X. Advances in Oral Drug Delivery Systems: Challenges and Opportunities. Pharmaceutics. 2023;15(2):484.
- Dingsdag SA, Hunter N. Metronidazole: An Update on Metabolism, Structure-Cytotoxicity and Resistance Mechanisms. J Antimicrob Chemother. 2018;73(2):265–279.
- Ellis C, Odunayo A, Tolbert MK. The Use of Metronidazole in Acute Diarrhea in Dogs: A Narrative Review. Top Companion Anim Med. 2023;56–57:100824.
- Afzal A. Bal AM. Metronidazole. Compr Pharmacol Seven Vol. set. 2022;7(V7):313-V7:321.
- Wang YL, Gómez-Avilés A, Zhang S, Rodriguez JJ, Bedia J, Belver C. Metronidazole Photodegradation under Solar Light with UiO-66-NH2 Photocatalyst: Mechanisms, Pathway, and Toxicity Assessment. J Environ Chem Eng. 2023;11(3).
- Sørensen CG, Karlsson WK, Amin FM, Lindelof M. Metronidazole-Induced Encephalopathy: A Systematic Review. J Neurol. 2020;267(1):1–13.
- Hernández Ceruelos A, Romero-Quezada LC, Ruvalcaba Ledezma JC, López Contreras L. Therapeutic Uses of Metronidazole and Its Side Effects: An Update. Eur Rev Med Pharmacol Sci. 2019;23(1):397–401.
- Iravani S, Varma RS. Nanosponges for Drug Delivery and Cancer Therapy: Recent Advances. Nanomaterials (Basel). 2022;12(14):2440.
- Utzeri G, Matias PMC, Murtinho D, Valente AJM. Cyclodextrin-Based Nanosponges: Overview and Opportunities. Front Chem. 2022;10:859406.
- Iravani S, Varma RS. Nanosponges for Water Treatment: Progress and Challenges. Appl Sci. 2022;12(9).
- Zhang Q, Honko A, Zhou J, Gong H, Downs SN, Vasquez JH, et al. Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity. Nano Lett. 2020;20(7):5570–5574.
- Bhowmik H, Venkatesh DN, Kuila A, Kumar KH. Nanosponges: A Review. Int J Appl Pharm. 2018;10(4):1–5.
- J A, Girigoswami A, Girigoswami K. Versatile Applications of Nanosponges in Biomedical Field: A Glimpse on SARS-CoV-2 Management. BioNanoScience. 2022;12(3):1018–1031.
- Sherje AP, Dravyakar BR, Kadam D, Jadhav M. Cyclodextrin-Based Nanosponges: A Critical Review. Carbohydr Polym. 2017;173:37–49.
- Utomo SB, Prabawati SY, Wahyuni I, VH ES, Mulyani S, Setyowati WA, et al. Inhibition Profile of Calix (4) Resorcinarene against Formation of Calcium Sulfate. Adv J Chem. 2025;8(12)(A):1876–1889.
- Dullah AAM, Daud A, Mallongi A, Zakir M, Jafar N, Indar, et al. Microplastics in Marine Biota and Human Health Risk in the Coastal Area. Adv J Chem Sect A. 2025;8(8):1329–1343.
- Abed AA, Banimuslem HA, Hassoni MH. Preparation of Copper Oxide Nanoparticles and Measurement of Their Effect on Bacterial Biofilm Formation. Adv J Chem Sect A. 2025;8(6):1043–1054.
- Akib S, Faizan S, Ahmed A, Khan GJ. Development and Physicochemical Characterization of Solid Lipid Nanoparticles Containing Tinidazole. J PharmSci Comput Chem. 2023;1(3):88–95.
- Soumya P, Sofi SI, Vignanandam S, Aishwarya B, Kholi CB, Anusha K, et al. A Study to Assess the Efficacy of Various Therapeutic Strategies Used in the Treatment of Psoriasis. J PharmSci Comput Chem. 2025;1(1):38–49.
- Prohit PV, Pakhare PS, Pawar VB, Dandade SS, Waghmare MS, Shaikh FA, et al. Formulation and Comparative Evaluation of Naproxen-Based Transdermal Gels. J PharmSci Comput Chem. 2025;1(2):83–105.
- Gopalaiah SB, Jayaseelan K. Quality-by-Design Guided Development, Optimization and Characterization of Irbesartan-Loaded Chitosan Nanoparticles: A Novel Antihypertensive Drug Delivery System. J Med Pharm Chem Res. 2025;7(11):2574–2595.
- Reddy SH, Manimaran V. In-Vitro and in-Vivo Evaluation of Doxycycline Hyclate and Piroxicam Loaded Chitosan Nanoparticles into Transdermal Patch for Healing Diabetic Foot Ulcer. J Med Pharm Chem Res. 2025;7(3):357–383.
- Susanti G, Aldi Y, Handayani D, Ismed F, Setiawansyah A. Chemical and Pharmacological Potential of Ficus elastica Fractions for Anti-hyperlipidemia: An Integrative Analysis from Molecular Docking, In Vitro, and in Vivo Chem Methodol. 2025;9(8):691–701.
- Çakar E, Çakar S, Toibazarova A, Syzdykbayev M, Sydykova G, Appazov N, et al. Dye Sensitized Solar Cells Applications of Ruhemann’s Purple Metal Complexes. Chem Methodol. 2025;9:1143–1153.
- Bajaj H, Sobuj DR, Qureshi MS, Sharma N, Singh LP, Boggula N, et al. Green Extraction and in Vivo Screening of Myrica Nagi Bark for Antidepressant, Antidiabetic, and Analgesic Potentials. Asian J Green Chem. 2026;10:69–83.
- Shah PA, Syed HK, Sohail AR, Pervaiz A, Iqbal MS, Liew KB, et al. Comparison of Solvent Evaporation and Ultrasonic-Assisted Production Methods in the Development of Nimesulide Nanosponges and Their Characterization. Trop J Pharm Res. 2022;21(6):1139–1145.
- Pawar Y A, R. Jadhav K, Rao JB, Tapkir AD, Malpure PS, Bachhav RS. Development and Characterization of Griseofulvin Nanosponges to Enhance Bioavailability. Int J Life Sci Pharma Res. 2022;P99–111.
- Shaikh SS, Deshmukh SA, Satpute RB, Pawar VV, Gangurde HH. Formulation and Evaluation of Green Tea-Based Herbal Anti-aging Cream for Effective Skin Care. J PharmSci Comput Chem. 2025;1(2):69–82.