Formulation Development, Characterization and Antifungal Evaluation of Chitosan NPs for Topical Delivery of Voriconazole In Vitro and Ex Vivo

doi:10.3390/polym14010135

. 2021 Dec 30;14(1):135.

doi: 10.3390/polym14010135.

Formulation Development, Characterization and Antifungal Evaluation of Chitosan NPs for Topical Delivery of Voriconazole In Vitro and Ex Vivo

Affiliations

¹ Advanced Drug Delivery Lab, Gomal Center of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan.
² Pharmaceutical Technology Unit, Faculty of Pharmacy, AIMST University, Bedong 08100, Kedah, Malaysia.
³ Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Korea.
⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Biology Department, Faculty of Science, King Khalid University, Abha 61421, Saudi Arabia.
⁶ Zoology Department, Faculty of Science, Damanhour University, Damanhour 22511, Egypt.
⁷ Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁸ Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.

PMID: 35012154
PMCID: PMC8747354
DOI: 10.3390/polym14010135

Formulation Development, Characterization and Antifungal Evaluation of Chitosan NPs for Topical Delivery of Voriconazole In Vitro and Ex Vivo

Muhammad Khurshid Alam Shah et al. Polymers (Basel). 2021.

. 2021 Dec 30;14(1):135.

doi: 10.3390/polym14010135.

Affiliations

¹ Advanced Drug Delivery Lab, Gomal Center of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan.
² Pharmaceutical Technology Unit, Faculty of Pharmacy, AIMST University, Bedong 08100, Kedah, Malaysia.
³ Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Korea.
⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Biology Department, Faculty of Science, King Khalid University, Abha 61421, Saudi Arabia.
⁶ Zoology Department, Faculty of Science, Damanhour University, Damanhour 22511, Egypt.
⁷ Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁸ Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.

PMID: 35012154
PMCID: PMC8747354
DOI: 10.3390/polym14010135

Abstract

This study aims to develop chitosan-based voriconazole nanoparticles (NPs) using spray-drying technique. The effect of surfactants and polymers on the physicochemical properties, in vitro release, and permeation of NPs was investigated. The prepared NPs containing various surfactants and polymers (e.g., Tween 20 (T20), Tween 80 (T80), sodium lauryl sulfate (SLS), propylene glycol (PG), and Polyethylene glycol-4000 (PEG-4000)) were physiochemically evaluated for size, zeta potential, drug content, percent entrapment efficiency, in vitro release, and permeation across rats' skin. A Franz diffusion cell was used for evaluating the in vitro release and permeation profile. The voriconazole-loaded NPs were investigated for antifungal activity against Candida albicans (C. albicans). The prepared NPs were in the nano range (i.e., 160-500 nm) and positively charged. Images taken by a scanning electron microscope showed that all prepared NPs were spherical and smooth. The drug content of NPs ranged from 75% to 90%. Nanoparticle formulations exhibited a good in vitro release profile and transport voriconazole across the rat's skin in a slow control release manner. The NPs containing SLS, T80, and PG exhibited the best penetration and skin retention profile. In addition, the formulation exhibited a potential antifungal effect against C. albicans. It was concluded that the development of chitosan NPs has a great potential for the topical delivery of voriconazole against fungal infection.

Keywords: PEG-4000; PG; chitosan; polymers; topical delivery; voriconazole.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
FTIR spectra of (a) VRZNA, (b) VRZNB, (c) VRZNC, (d) VRZND, (e) VRZNE, (f) VRZNF, and (g) VRZNG.

**Figure 2**
Particle size distribution (a) and SEM morphology of chitosan NPs containing voriconazole of formulation VRZNC (b).

**Figure 3**
In vitro average of % drug release of formulations: n = 3, mean ± S.D., * p < 0.05 considered statistically significantly different from VRZNB, VRZND, VRZNE, VRZNF, and VRZNG.

**Figure 4**
In vitro average of % permeation of formulations: n = 3, mean ± S.D., * p < 0.05 considered statistically significantly different from VRZNB, VRZNC, VRZNE, VRZNF, and VRZNG.

**Figure 5**
% Drug retention of different formulations: n = 3, mean ± S.D., * p < 0.05 and ** p < 0.001 considered statistically significantly different from VRZNA, VRZNE, and VRZNF.

**Figure 6**
ATR-FTIR of skin epidermis: (a) blank skin, (b) skin treated with formulation VRZNA, (c) skin treated with formulation VRZNB, (d) skin treated with formulation VRZNC, (e) skin treated with formulation VRZND, (f) skin treated with formulation VRZNE, (g) skin treated with formulation VRZNF, (h) skin treated with formulation VRZNG, and (i) skin treated with pure drug.

**Figure 7**
ATR-FTIR of skin dermis: (a) blank skin, (b) skin treated with formulation VRZNA, (c) skin treated with formulation VRZNB, (d) skin treated with formulation VRZNC, (e) skin treated with formulation VRZND, (f) skin treated with formulation VRZNE, (g) skin treated with formulation VRZNF, (h) skin treated with formulation VRZNG, and (i) skin treated with pure drug.

**Figure 8**
In vitro antifungal activity of drug vehicle, chitosan NPs, and voriconazole-loaded chitosan NPs against *C. albicans*: n = 3, mean ± S.D., * p < 0.05 and ** p < 0.001 considered statistically significant different from without drug-loaded chitosan nanoparticles.

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References

1. Qurt M.S., Esentürk İ., Tan S.B., Erdal M.S., Araman A., Güngör S. Voriconazole and sertaconazole loaded colloidal nano-carriers for enhanced skin deposition and improved topical fungal treatment. J. Drug Deliv. Sci. Technol. 2018;48:215–222. doi: 10.1016/j.jddst.2018.09.020. - DOI
1. Kumar R., Sinha V.R. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf. B Biointerfaces. 2014;117:82–88. doi: 10.1016/j.colsurfb.2014.02.007. - DOI - PubMed
1. Latif M.S., Azad A.K., Nawaz A., Rashid S.A., Rahman M., Al Omar S.Y., Bungau S.G., Aleya L., Abdel-Daim M.M. Ethyl Cellulose and Hydroxypropyl Methyl Cellulose Blended Methotrexate-Loaded Transdermal Patches: In Vitro and Ex Vivo. Polymers. 2021;13:3455. doi: 10.3390/polym13203455. - DOI - PMC - PubMed
1. Zonios D.I., Bennett J.E. Update on azole antifungals. Semin. Respir. Crit. Care Med. 2008;29:198–210. doi: 10.1055/s-2008-1063858. - DOI - PubMed
1. El-Hadidy G.N., Ibrahim H.K., Mohamed M.I., El-Milligi M.F. Microemulsions as vehicles for topical administration of voriconazole: Formulation and in vitro evaluation. Drug Dev. Ind. Pharm. 2012;38:64–72. doi: 10.3109/03639045.2011.590731. - DOI - PubMed

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TURSP-2020/153 and R.G.P.2/80/41/Taif University Researchers Supporting Program and Deanship of Scientific Research at King Khalid University, Abha, KSA

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[1] Qurt M.S., Esentürk İ., Tan S.B., Erdal M.S., Araman A., Güngör S. Voriconazole and sertaconazole loaded colloidal nano-carriers for enhanced skin deposition and improved topical fungal treatment. J. Drug Deliv. Sci. Technol. 2018;48:215–222. doi: 10.1016/j.jddst.2018.09.020. - DOI

[2] Qurt M.S., Esentürk İ., Tan S.B., Erdal M.S., Araman A., Güngör S. Voriconazole and sertaconazole loaded colloidal nano-carriers for enhanced skin deposition and improved topical fungal treatment. J. Drug Deliv. Sci. Technol. 2018;48:215–222. doi: 10.1016/j.jddst.2018.09.020. - DOI

[3] Kumar R., Sinha V.R. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf. B Biointerfaces. 2014;117:82–88. doi: 10.1016/j.colsurfb.2014.02.007. - DOI - PubMed

[4] Kumar R., Sinha V.R. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf. B Biointerfaces. 2014;117:82–88. doi: 10.1016/j.colsurfb.2014.02.007. - DOI - PubMed

[5] Latif M.S., Azad A.K., Nawaz A., Rashid S.A., Rahman M., Al Omar S.Y., Bungau S.G., Aleya L., Abdel-Daim M.M. Ethyl Cellulose and Hydroxypropyl Methyl Cellulose Blended Methotrexate-Loaded Transdermal Patches: In Vitro and Ex Vivo. Polymers. 2021;13:3455. doi: 10.3390/polym13203455. - DOI - PMC - PubMed

[6] Latif M.S., Azad A.K., Nawaz A., Rashid S.A., Rahman M., Al Omar S.Y., Bungau S.G., Aleya L., Abdel-Daim M.M. Ethyl Cellulose and Hydroxypropyl Methyl Cellulose Blended Methotrexate-Loaded Transdermal Patches: In Vitro and Ex Vivo. Polymers. 2021;13:3455. doi: 10.3390/polym13203455. - DOI - PMC - PubMed

[7] Zonios D.I., Bennett J.E. Update on azole antifungals. Semin. Respir. Crit. Care Med. 2008;29:198–210. doi: 10.1055/s-2008-1063858. - DOI - PubMed

[8] Zonios D.I., Bennett J.E. Update on azole antifungals. Semin. Respir. Crit. Care Med. 2008;29:198–210. doi: 10.1055/s-2008-1063858. - DOI - PubMed

[9] El-Hadidy G.N., Ibrahim H.K., Mohamed M.I., El-Milligi M.F. Microemulsions as vehicles for topical administration of voriconazole: Formulation and in vitro evaluation. Drug Dev. Ind. Pharm. 2012;38:64–72. doi: 10.3109/03639045.2011.590731. - DOI - PubMed

[10] El-Hadidy G.N., Ibrahim H.K., Mohamed M.I., El-Milligi M.F. Microemulsions as vehicles for topical administration of voriconazole: Formulation and in vitro evaluation. Drug Dev. Ind. Pharm. 2012;38:64–72. doi: 10.3109/03639045.2011.590731. - DOI - PubMed

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Formulation Development, Characterization and Antifungal Evaluation of Chitosan NPs for Topical Delivery of Voriconazole In Vitro and Ex Vivo

Affiliations

Formulation Development, Characterization and Antifungal Evaluation of Chitosan NPs for Topical Delivery of Voriconazole In Vitro and Ex Vivo

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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References

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Abstract

Conflict of interest statement

Figures

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References

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