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. 2025 Mar;15(3):885-907.
doi: 10.1007/s13346-024-01642-6. Epub 2024 Jun 5.

Topical gel formulations as potential dermal delivery carriers for green-synthesized zinc oxide nanoparticles

Rania Hamed  1 , Ruwa Z Obeid  2 , Rana Abu Huwaij  3 , Duaa Qattan  4 , Nisreen Abu Shahin  5
Affiliations

Topical gel formulations as potential dermal delivery carriers for green-synthesized zinc oxide nanoparticles

Rania Hamed et al. Drug Deliv Transl Res. 2025 Mar.

Abstract

This study aimed to incorporate green-synthesized zinc oxide nanoparticles (ZnO NPs), functionalized with polyethylene glycol (PEG) and linked to doxorubicin (DOX), into various topical gel formulations (hydrogel, oleogel, and bigel) to enhance their dermal delivery. The ZnO NPs were produced using the aqueous extract of the root hair of Phoenix dactylifera. The optimized green-synthesized ZnO NPs, PEGylated and conjugated to DOX, demonstrated a particle size below 100 nm, low polydispersity index, and zeta potential between - 11 and - 19 mV. The UV-Vis spectroscopy analysis confirmed characteristic absorption peaks at 351 and 545 nm for ZnO and DOX, respectively. The transmission electron microscope (TEM) images revealed well-dispersed spherical nanoparticles without aggregation. Additionally, ZnO NPs-loaded gels exhibited uniformity, cohesion, no phase separation, pseudoplastic flow, and viscoelastic properties. The in vitro release studies showed that DOX-PEG-ZnO NPs hydrogel released 99.5% of DOX after 5 h of starting the release. Moreover, the penetration of DOX-PEG-ZnO NPs through excised rat skin was visualized by TEM. In conclusion, the hydrogel formulation containing green-synthesized DOX-PEG-ZnO NPs holds great promise for dermal administration in skin cancer treatment. Furthermore, the release rate and skin penetration of DOX from gels were varied based on the type of gel matrix and corroborated with their corresponding rheological properties.

Keywords: Bigel; Doxorubicin HCl; Green synthesis; Hydrogel; Oleogel; PEGylated ZnO NPs; Skin penetration; Zinc oxide nanoparticles.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All institutional and national guidelines for the care and use of laboratory animals were followed. Three male Wistar rats aged 3–4 months and weighing 180–220 g were obtained from the animal breeding facility at Jordan University of Science and Technology (Irbid, Jordan). Rats were kept in small plastic cages (one rat per cage) under hygienic conditions. The rats were left for 3 days at room temperature to acclimatize to a new environment. They were housed in an air-conditioned room at a temperature of ~ 22 ºC with standard pellet feed and water ad libitum. The study procedure was reviewed and approved by the Research Ethics Committee at Al-Zaytoonah University of Jordan (IRB# 10/05/2022–2023). The rats were anesthetized with diethyl ether and then killed by cervical dislocation. The dorsal region of the rat skin was carefully shaved. Consent for publication: All authors read and approved the final manuscript and agree with its publication. Competing interests: The authors declare no competing interests.

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