Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer

Elhabal, Sammar Fathy; Faheem, Ahmed Mohsen; Hababeh, Sandra; Nelson, Jakline; Elzohairy, Nahla A.; Ibrahim, Yasmine F.; Ewedah, Tassneim M.; Mousa, Ibrahim S.; Allam, Khaled M.; Hamdan, Ahmed Mohsen Elsaid

doi:10.3390/pharmaceutics17050611

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Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer

by

Sammar Fathy Elhabal

^1,*

,

Ahmed Mohsen Faheem

²,

Sandra Hababeh

³

,

Jakline Nelson

⁴,

Nahla A. Elzohairy

^5,6,

Yasmine F. Ibrahim

^7,8,

Tassneim M. Ewedah

⁹,

Ibrahim S. Mousa

¹⁰,

Khaled M. Allam

¹¹

and

Ahmed Mohsen Elsaid Hamdan

^12,*

¹

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt

²

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt

³

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

⁴

Department of Microbiology and Immunology, Faculty of Pharmacy, Nahda University, Beni-Suef (NUB), Beni-Suef 62511, Egypt

⁵

Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt

⁶

Air Force Specialized Hospital, Cairo 19448, Egypt

⁷

Department of Medical Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt

⁸

Pathological Sciences Department-MBBS Program, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia

⁹

Pharmaceutics and Pharmaceutical Technology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt

¹⁰

Pharmaceutics Department, Faculty of Pharmacy, Sinai University, Al-Arish 45511, Egypt

¹¹

Department of Pharmacognosy, Faculty of Pharmacy, South Valley University, Qena 83523, Egypt

¹²

Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia

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^*

Authors to whom correspondence should be addressed.

Pharmaceutics 2025, 17(5), 611; https://doi.org/10.3390/pharmaceutics17050611

Submission received: 5 April 2025 / Revised: 27 April 2025 / Accepted: 29 April 2025 / Published: 5 May 2025

(This article belongs to the Special Issue Biofunctional Pharmaceutical Additives for Targeted, Improved Bioavailability and Safety of Medicine)

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Abstract

Background/Objectives: Diabetic mouth ulcers are a pathological condition of the oral mucosa leading to increases in susceptibility to infection and prolonged wound healing time. Still, there is a lack of natural formulations for treating this condition. Our principal objective was to formulate solid lipid nanoparticles (SLNs) that contained Althaea officinalis (marshmallow) (M.) extract with clove oil (CO.), subsequently integrated into a collagen sponge for enhancing stability, solubility, sustained release, antimicrobial efficacy, and healing power when targeting diabetic oral ulcers. Methods: A factorial design of 34 trials was established to evaluate the influence of lipid concentration (A), SAA concentration (B), lipid type (C), and SAA type (D). The optimized M-CO-SLNs was selected using Design Expert^®, the based Poly dispersibility index (Y2), zeta potential (MV) (Y3), and encapsulation efficiency (%) (Y4). The optimized SLNs were integrated into a collagen sponge matrix and tested for their antibacterial and antifungal efficacy against Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, respectively. Moreover, they were tested for their wound healing power in a diabetic mouth ulcer model. Results: The optimized formula (Run 16: 5% lipid concentration, 4% SAA concentration, capric acid) demonstrated P.S (110 ± 0.76 nm), ZP (−24 ± 0.32 mV), PDI (0.18 ± 0.05), and EE% (90 ± 0.65%.). The optimized M-CO-SLNs formula was incorporated into a cross-linked collagen sponge and showed superior antimicrobial efficacy, an increased swelling ratio, and was effective in an in vivo oral ulcer study, as evidenced by ELISA biomarkers, gene expression analysis, and histological analysis. Conclusions: M-CO-SLNs embedded in collagen sponges is a promising therapeutic formula for clinical application against diabetic mouth ulcers.

Keywords: Althaea officinalis; anti-inflammatory; clove oil; collagen sponge; diabetic mouth ulcers; solid lipid nanoparticles; oral mucosal drug delivery; Pseudomonas aeruginosa; Escherichia coli; Candida albicans

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MDPI and ACS Style

Elhabal, S.F.; Faheem, A.M.; Hababeh, S.; Nelson, J.; Elzohairy, N.A.; Ibrahim, Y.F.; Ewedah, T.M.; Mousa, I.S.; Allam, K.M.; Hamdan, A.M.E. Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer. Pharmaceutics 2025, 17, 611. https://doi.org/10.3390/pharmaceutics17050611

AMA Style

Elhabal SF, Faheem AM, Hababeh S, Nelson J, Elzohairy NA, Ibrahim YF, Ewedah TM, Mousa IS, Allam KM, Hamdan AME. Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer. Pharmaceutics. 2025; 17(5):611. https://doi.org/10.3390/pharmaceutics17050611

Chicago/Turabian Style

Elhabal, Sammar Fathy, Ahmed Mohsen Faheem, Sandra Hababeh, Jakline Nelson, Nahla A. Elzohairy, Yasmine F. Ibrahim, Tassneim M. Ewedah, Ibrahim S. Mousa, Khaled M. Allam, and Ahmed Mohsen Elsaid Hamdan. 2025. "Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer" Pharmaceutics 17, no. 5: 611. https://doi.org/10.3390/pharmaceutics17050611

APA Style

Elhabal, S. F., Faheem, A. M., Hababeh, S., Nelson, J., Elzohairy, N. A., Ibrahim, Y. F., Ewedah, T. M., Mousa, I. S., Allam, K. M., & Hamdan, A. M. E. (2025). Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer. Pharmaceutics, 17(5), 611. https://doi.org/10.3390/pharmaceutics17050611

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Augmented Marshmallow Extract Lipid Nanoparticles with Clove Oil Embedded in Collagen Sponge for Ultimate Antimicrobial Healing of Diabetic Mouth Ulcer

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