Development of Apremilast Nanoemulsion-Loaded Chitosan Gels: In Vitro Evaluations and Anti-Inflammatory and Wound Healing Studies on a Rat Model

Overview

Journal Gels

Date 2022 May 27

PMID 35621551

Authors

Mohammed Muqtader Ahmed

Md Khalid Anwer

Farhat Fatima

Amer S Alali

Mohd Abul Kalam

Ameeduzzafar Zafar

Sultan Alshehri

Mohammed M Ghoneim

Affiliations

Soon will be listed here.

Abstract

Apremilast (APL) has profound anti-inflammatory and wound healing activity, alongside other dermal care. This study aims to develop APL-loaded NEs (ANE1-ANE5) using eucalyptus oil (EO) as the oil and Tween-80 and transcutol-HP (THP) as a surfactant and co-surfactant, respectively. The prepared NEs were then evaluated based on mean droplet size (12.63 ± 1.2 nm), PDI (0.269 ± 0.012), ZP (-23.00 ± 5.86), RI (1.315 ± 0.02), and %T (99.89 ± 0.38) and ANE4 was optimized. Further, optimized NEs (ANE4) were incorporated into chitosan gel (2%, ). The developed ANE4-loaded chitosan gel was then evaluated for pH, spreadability, in vitro diffusion, and wound healing and anti-inflammatory studies. Moreover, in vivo studies denoted improved anti-inflammatory and wound healing activity and represented a decrease in wound size percentage (99.68 ± 0.345%) for the APNE2 gel test compared to a negative control (86.48 ± 0.87%) and standard control (92.82 ± 0.34%). Thus, the formulation of ANE4-loaded chitosan gels is an efficient topical treatment strategy for inflammatory and wound healing conditions.

Citing Articles

Understanding Microemulsions and Nanoemulsions in (Trans)Dermal Delivery.

Musakhanian J, Osborne D AAPS PharmSciTech. 2025; 26(1):31.

PMID: 39794642 DOI: 10.1208/s12249-024-02997-2.

A poly-δ-decalactone (PDL) based nanoemulgel for topical delivery of ketoconazole and eugenol against .

Dubey P, Kumar A, Vaiphei K, Basrani S, Jadhav A, Wilen C Nanoscale Adv. 2024; .

PMID: 39247866 PMC: 11376195. DOI: 10.1039/d4na00176a.

Bilateral punctate keratitis and hurricane keratopathy following apremilast therapy.

Wolfel L, Franco J, Gillette T, Chodosh J, Davis A Am J Ophthalmol Case Rep. 2024; 32:101905.

PMID: 38161516 PMC: 10757167. DOI: 10.1016/j.ajoc.2023.101905.

Enhanced Apigenin Dissolution and Effectiveness Using Glycyrrhizin Spray-Dried Solid Dispersions Filled in 3D-Printed Tablets.

Omer A, Fatima F, Ahmed M, Aldawsari M, Alalaiwe A, Anwer M Biomedicines. 2023; 11(12).

PMID: 38137562 PMC: 10742019. DOI: 10.3390/biomedicines11123341.

Diosmin-Loaded Nanoemulsion-Based Gel Formulation: Development, Optimization, Wound Healing and Anti-Inflammatory Studies.

Anwer M, Aldawsari M, Iqbal M, Almutairy B, Soliman G, Aboudzadeh M Gels. 2023; 9(2).

PMID: 36826265 PMC: 9956956. DOI: 10.3390/gels9020095.

References

Jaiswal M, Dudhe R, Sharma P . Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech. 2017; 5(2):123-127. PMC: 4362737. DOI: 10.1007/s13205-014-0214-0. View

Zhao D, Zhang R, Liu X, Li X, Xu M, Huang X . Screening of Chitosan Derivatives-Carbon Dots Based on Antibacterial Activity and Application in Anti- Biofilm. Int J Nanomedicine. 2022; 17:937-952. PMC: 8904944. DOI: 10.2147/IJN.S350739. View

Diaz D, Colgan S, Langer C, Bandi N, Likar M, Van Alstine L . Dissolution Similarity Requirements: How Similar or Dissimilar Are the Global Regulatory Expectations?. AAPS J. 2015; 18(1):15-22. PMC: 4706290. DOI: 10.1208/s12248-015-9830-9. View

Elmore S . Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4):495-516. PMC: 2117903. DOI: 10.1080/01926230701320337. View

Thomas L, Zakir F, Aamir Mirza M, Anwer M, Ahmad F, Iqbal Z . Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies. Int J Biol Macromol. 2017; 101:569-579. DOI: 10.1016/j.ijbiomac.2017.03.066. View

Dainichi T, Hanakawa S, Kabashima K . Classification of inflammatory skin diseases: a proposal based on the disorders of the three-layered defense systems, barrier, innate immunity and acquired immunity. J Dermatol Sci. 2014; 76(2):81-9. DOI: 10.1016/j.jdermsci.2014.08.010. View

Xue Z, Fu R, Duan Z, Chi L, Zhu C, Fan D . Inhibitory Effect of pH-Responsive Nanogel Encapsulating Ginsenoside CK against Lung Cancer. Polymers (Basel). 2021; 13(11). PMC: 8198720. DOI: 10.3390/polym13111784. View

Hussain A, Samad A, Singh S, Ahsan M, Haque M, Faruk A . Nanoemulsion gel-based topical delivery of an antifungal drug: in vitro activity and in vivo evaluation. Drug Deliv. 2014; 23(2):642-47. DOI: 10.3109/10717544.2014.933284. View

Wang B, Sun W, Bi K, Li Y, Li F . Apremilast prevents IL‑17‑induced cellular senescence in ATDC5 chondrocytes mediated by SIRT1. Int J Mol Med. 2021; 47(3). PMC: 7834959. DOI: 10.3892/ijmm.2021.4845. View

10.

Wu Z, Zhou W, Deng W, Xu C, Cai Y, Wang X . Antibacterial and Hemostatic Thiol-Modified Chitosan-Immobilized AgNPs Composite Sponges. ACS Appl Mater Interfaces. 2020; 12(18):20307-20320. DOI: 10.1021/acsami.0c05430. View

11.

Anwer M, Mohammad M, Ezzeldin E, Fatima F, Alalaiwe A, Iqbal M . Preparation of sustained release apremilast-loaded PLGA nanoparticles: in vitro characterization and in vivo pharmacokinetic study in rats. Int J Nanomedicine. 2019; 14:1587-1595. PMC: 6402442. DOI: 10.2147/IJN.S195048. View

12.

Shafiq-Un-Nabi S, Shakeel F, Talegaonkar S, Ali J, Baboota S, Ahuja A . Formulation development and optimization using nanoemulsion technique: a technical note. AAPS PharmSciTech. 2007; 8(2):Article 28. PMC: 2750368. DOI: 10.1208/pt0802028. View

13.

Kong B, Kim A, Park S . Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin. Carbohydr Polym. 2016; 147:473-481. DOI: 10.1016/j.carbpol.2016.04.021. View

14.

Lim J, Ng N, Thomas C . Prevention and treatment of diabetic foot ulcers. J R Soc Med. 2017; 110(3):104-109. PMC: 5349377. DOI: 10.1177/0141076816688346. View

15.

Fatima F, Aldawsari M, Ahmed M, Anwer M, Naz M, Javed Ansari M . Green Synthesized Silver Nanoparticles Using Tridax Procumbens for Topical Application: Excision Wound Model and Histopathological Studies. Pharmaceutics. 2021; 13(11). PMC: 8623640. DOI: 10.3390/pharmaceutics13111754. View

16.

Sarango-Granda P, Silva-Abreu M, Calpena A, Halbaut L, Fabrega M, Rodriguez-Lagunas M . Apremilast Microemulsion as Topical Therapy for Local Inflammation: Design, Characterization and Efficacy Evaluation. Pharmaceuticals (Basel). 2020; 13(12). PMC: 7767333. DOI: 10.3390/ph13120484. View

17.

Nastiti C, Ponto T, Abd E, Grice J, Benson H, Roberts M . Topical Nano and Microemulsions for Skin Delivery. Pharmaceutics. 2017; 9(4). PMC: 5750643. DOI: 10.3390/pharmaceutics9040037. View

18.

Field K, White W, Lang C . Anaesthetic effects of chloral hydrate, pentobarbitone and urethane in adult male rats. Lab Anim. 1993; 27(3):258-69. DOI: 10.1258/002367793780745471. View

19.

Demisli S, Mitsou E, Pletsa V, Xenakis A, Papadimitriou V . Development and Study of Nanoemulsions and Nanoemulsion-Based Hydrogels for the Encapsulation of Lipophilic Compounds. Nanomaterials (Basel). 2020; 10(12). PMC: 7763598. DOI: 10.3390/nano10122464. View

20.

Tao Q, Zhong J, Wang R, Huang Y . Ionic and Enzymatic Multiple-Crosslinked Nanogels for Drug Delivery. Polymers (Basel). 2021; 13(20). PMC: 8541401. DOI: 10.3390/polym13203565. View