Formulation, optimization and characterization of apremilast-loaded nanosponges for potential topical wound management applications

Purnima Rai; Ajay Kumar Singh  Rawat

doi:10.69857/joapr.v14i4.2153

Authors

Purnima Rai Maharishi School of Pharmaceutical Sciences, Maharishi University of Information Technology, Lucknow, Uttar Pradesh, 226013, India
Ajay Kumar Singh Rawat Maharishi School of Pharmaceutical Sciences, Maharishi University of Information Technology, Lucknow, Uttar Pradesh, 226013, India

DOI:

https://doi.org/10.69857/joapr.v14i4.2153

Keywords:

Apremilast, Nanosponges, Wound management, Topical delivery, Sustained drug release, entrapment efficiency

Abstract

Background: Topical drug delivery systems provide site-specific therapy with reduced systemic exposure. Nanosponges have emerged as promising carriers owing to their porous structure, enabling improved drug stability, bioavailability, and sustained release. Apremilast, a phosphodiesterase-4 (PDE4) inhibitor with anti-inflammatory activity, has potential for topical wound management when formulated as a controlled-release delivery system. Methods: Apremilast-loaded nanosponges were prepared by the emulsion solvent diffusion method using Ethyl Cellulose (EC) and Polyvinyl Alcohol (PVA). A 3² factorial design was used to optimize the EC: PVA ratio and sonication time. Formulations were evaluated for particle size, entrapment efficiency, zeta potential, in vitro drug release, and surface morphology. Characterization included UV spectroscopy, FTIR, XRD, DSC, and SEM. Drug release kinetics were analyzed using mathematical models. Results: Preformulation studies confirmed drug purity and compatibility with excipients. The optimized formulation (NS8) exhibited a particle size of 213.85 nm, an entrapment efficiency of 82.75%, a zeta potential of −33.3 mV, and a sustained drug release of 95.85% over 24 h. SEM revealed spherical porous nanosponges, while FTIR, XRD, and DSC confirmed drug integrity and formulation stability. Response surface analysis demonstrated significant effects of formulation variables on performance. Drug release followed the Higuchi model (R² = 0.987), and the Korsmeyer–Peppas exponent (n = 0.58) indicated anomalous non-Fickian diffusion. Conclusion: Apremilast-loaded nanosponges demonstrated sustained drug release, excellent stability, and favorable physicochemical characteristics, indicating their potential as an effective topical delivery system for wound management. Further ex vivo, in vivo, and clinical studies are required to confirm therapeutic efficacy and safety.

Downloads

Download data is not yet available.

References

Sen CK. Human wound and its burden: Updated 2022 compendium of estimates. Adv. Wound Care (New Rochelle)., 12(12), 657–670 (2023) https://doi.org/10.1089/wound.2023.0150

Olsson M, Järbrink K, Divakar U, Bajpai R, Upton Z, Schmidtchen A, et al. The humanistic and economic burden of chronic wounds: A systematic review (update). Wound Repair Regen., 31(1), 1–13 (2023) https://doi.org/10.1111/wrr.13077

Wilkinson HN, Hardman MJ. Wound healing: Cellular mechanisms and pathological outcomes. Open Biol., 10(9), 200223 (2020) https://doi.org/10.1098/rsob.200223

Eming SA, Murray PJ, Pearce EJ. Metabolic orchestration of the wound healing response. Cell Metab., 33(9), 1726–1743 (2021) https://doi.org/10.1016/j.cmet.2021.07.017

Lambi AG, DeSante RJ, Patel PR, Hilliard BA, Popoff SN, Barbe MF. Blocking CCN2 reduces established palmar neuromuscular fibrosis and improves function following repetitive overuse injury. Int. J. Mol. Sci., 24(18), 13866 (2023) https://doi.org/10.3390/ijms241813866

Khanam S. A systematic review on wound healing and its promising medicinal plants. IP Int. J. Compr. Adv. Pharmacol., 5(3), 170–176 (2021) https://doi.org/10.18231/j.ijcap.2020.030

Benson HAE, Grice JE. Topical drug delivery: Principles and practice. Adv. Drug Deliv. Rev., 186, 114320 (2022) https://doi.org/10.1016/j.addr.2022.114320

Mohd Saeed, et al. Recent advances in topical drug delivery systems for skin disorders. Gels, 9(2), 123 (2023) https://doi.org/10.3390/gels9020123

Badran YAA, Kuntsche J, Fahr A. Skin penetration enhancement strategies in topical drug delivery. Pharmaceutics, 13(9), 1361 (2021) https://doi.org/10.3390/pharmaceutics13091361

Singh A, Verma A, Kumar P. Innovative nanostructured lipid carrier gel for enhanced topical delivery of roflumilast in psoriasis management. Journal of Applied Pharmaceutical Research, 13(4), 254-265 (2025) https://doi.org/10.69857/joapr.v13i4.1242

Swaminathan S, Vavia PR, Trotta F, Cavalli R. Nanosponges for drug delivery and biomedical applications: Recent progress. Gels, 9(3), 210 (2023) https://doi.org/10.3390/gels9030210

Shende PK, Gaud RS. Nanosponges: A potential nanocarrier for drug delivery. J. Drug Deliv. Sci. Technol., 53, 101187 (2019) https://doi.org/10.1016/j.jddst.2019.101187

Krishnamoorthy K, Mahalingam S. Nanosponges: A novel class of drug delivery system—Recent trends and advances. J. Drug Deliv. Sci. Technol., 68, 103043 (2022) https://doi.org/10.1016/j.jddst.2021.103043

Sakkas LI, Bogdanos DP. Apremilast: A novel PDE4 inhibitor for inflammatory diseases. Clin. Immunol., 226, 108730 (2021) https://doi.org/10.1016/j.clim.2021.108730

Papp K, Reich K, Paul C, et al. Apremilast in inflammatory dermatologic diseases: Updated clinical evidence. J. Am. Acad. Dermatol., 86(1), e1–e14 (2022) https://doi.org/10.1016/j.jaad.2021.05.067

Kaur IP, Aggarwal D, Singh H, Kakkar S. Nanosponges as a promising carrier for topical delivery of antifungal agents: Recent advances. J. Drug Deliv. Sci. Technol., 70, 103210 (2022) https://doi.org/10.1016/j.jddst.2022.103210

Luiz MT, Viegas JSR, Abriata JP, Viegas F, Vicentini FTMC, Bentley MVLB, et al. Design of experiments (DoE) to develop and optimize nanoparticles as drug delivery systems. Eur. J. Pharm. Biopharm., 165, 127–148 (2021) https://doi.org/10.1016/j.ejpb.2021.05.011

Tekade RK. Basic fundamentals of pharmaceutical formulation development and preformulation studies. Pharmaceutics, 13(10), 1684 (2021) https://doi.org/10.3390/pharmaceutics13101684

Rampado R, Peer D. Design of experiments in the optimization of nanoparticle-based drug delivery systems. J. Control. Release, 358, 398–419 (2023) https://doi.org/10.1016/j.jconrel.2023.05.001

Jain S, Shah RP. Drug-excipient compatibility study through a novel vial-in-vial experimental setup: A benchmark study. AAPS PharmSciTech, 24(5), 117 (2023) https://doi.org/10.1208/s12249-023-02573-0

Tkachenko Y, Niedzielski P. FTIR as a method for qualitative assessment of solid samples in geochemical research: A review. Molecules, 27(24), 8846 (2022) https://doi.org/10.3390/molecules27248846

Park YS, Choi J, Kim BS, et al. Synergistic effects of P and Si on the flame retardancy in a polymethyl silsesquioxane aerogel prepared under ambient pressure drying. J. Therm. Anal. Calorim., 148, 7623–7632 (2023) https://doi.org/10.1007/s10973-023-12244-8

Ponsar H, Quodbach J. Customizable 3D printed implants containing triamcinolone acetonide: Development, analysis, modification, and modeling of drug release. Pharmaceutics, 15(8), 2097 (2023) https://doi.org/10.3390/pharmaceutics15082097

Buya AB, Mahlangu P, Witika BA. From lab to industrial development of lipid nanocarriers using quality by design approach. Int. J. Pharm. X, Article 100266 (2024) https://doi.org/10.1016/j.ijpx.2024.100266

Khan I, Saeed K, Khan I. Nanoparticles: Properties, applications and toxicities. Arab. J. Chem., 12(7), 908–931 (2019) https://doi.org/10.1016/j.arabjc.2017.05.011