Propolis-Based Microneedles Incorporating Neratinib-Loaded Ocimum basilicum Essential Oil-Based Lipid Nanovesicles for Minimally Invasive Cancer Therapy: Formulation and In Vivo Evaluation in an Ehrlich Solid Tumor Model.
14 affiliations
- 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt.
- 2Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt.
- 3Pathological Sciences Department, MBBS Program, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia.
- 4Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST), 6th of October City 12566, Egypt.
- 5Department of Pharmacognosy, Faculty of Pharmacy, Qena University, Qena 83523, Egypt.
- 6Department of Physiology, General Medicine Practice Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia.
- 7Medical Physiology Department, Faculty of Medicine, Cairo University, Kasr Alainy, Giza 11562, Egypt.
- 8Pharmaceutics and Pharmaceutical Technology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt.
- 9Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt.
- 10Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria (PUA), Alexandria 21311, Egypt.
- 11Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
- 12Department of Clinical Pharmacy, Faculty of Pharmacy, Menoufia University, Menoufia 32811, Egypt.
- 13Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.
- 14Prince Fahad bin Sultan Chair for Biomedical Research (PFSCBR), Tabuk 74191, Saudi Arabia.
Abstract
Background: Neratinib (NTB) is a potent pan-HER inhibitor, but its oral bioavailability is limited due to poor aqueous solubility, low permeability, and gastrointestinal toxicity. This study incorporated a bioactive transdermal system by incorporating NTB-loaded nanovesicles of Ocimum basilicum oil (NTB-OOs) into dissolving microneedles of PVA/PVP-propolis. Methods: Ocimum basilicum oil was characterized by gas chromatography-mass spectrometry (GC-MS). NTB-OOs were screened by I-optimal design and evaluated for vesicular properties, stability, release, skin permeation, and cytotoxicity. The optimized vesicles were loaded in propolis microneedles and evaluated mechanically, ex vivo, and in MCF-7 cells and Ehrlich solid carcinoma-bearing mice. Results: GC-MS revealed a volatile profile rich in linalool, methyl jasmonate, and a cyclopenta[g]-2-benzopyran derivative with reported antioxidant and anticancer activities. The optimized NTB-OOs showed a particle size of (198.9 ± 0.98 nm), entrapment efficiency of (88.9 ± 0.45%), PDI of (0.16 ± 0.01), zeta potential of (-23.1 ± 0.35 mV), and six-month stability. The microneedles provided zero-order release (48-50% after 24 h) and ex vivo permeation (~3500 µg/cm²), which were 2.7- and 1.2-fold higher than those of the NTB suspension and NTB-OOs, respectively. NTB-OOs reduced MCF-7 IC₅₀ from 11.1 to 5.1 µg/mL. In vivo, NTB-OOs/propolis microneedles achieved 75.6% tumor inhibition, increased mean survival from 19 to 26.5 days, and raised the T/C ratio to 139.5%. They also induced apoptosis and downregulated the expression of HER-2, EGFR, VEGF-A, and Bcl-2. Conclusions: The multifunctional nanovesicle-propolis microneedle platform improves NTB solubilization, controlled release, dermal delivery, and antitumor efficacy, supporting its potential for minimally invasive localized breast cancer therapy.
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BibTeX
@article{elhabal2026propolisbased,
title = {{Propolis-Based Microneedles Incorporating Neratinib-Loaded Ocimum basilicum Essential Oil-Based Lipid Nanovesicles for Minimally Invasive Cancer Therapy: Formulation and In Vivo Evaluation in an Ehrlich Solid Tumor Model.}},
author = {Sammar Fathy Elhabal and Suzan Awad AbdelGhany Morsy and Marian Sobhy Azer and Khaled M Allam and Fatma E Hassan and Tassneim M Ewedah and Rania Mostafa Abd El Galil and Mahmoud Nour El-Din and Ahmed I Ashmawy and Heba Sabry Ahmed and Azza ElSayed Abd ElFattah Mansy and Ahmed Mohsen Elsaid Hamdan},
journal = {Pharmaceutics},
year = {2026},
month = sep,
doi = {10.3390/pharmaceutics18101244},
url = {https://europepmc.org/article/MED/42942776},
note = {CC BY},
}
RIS
TY - JOUR
TI - Propolis-Based Microneedles Incorporating Neratinib-Loaded Ocimum basilicum Essential Oil-Based Lipid Nanovesicles for Minimally Invasive Cancer Therapy: Formulation and In Vivo Evaluation in an Ehrlich Solid Tumor Model.
AU - Sammar Fathy Elhabal
AU - Suzan Awad AbdelGhany Morsy
AU - Marian Sobhy Azer
AU - Khaled M Allam
AU - Fatma E Hassan
AU - Tassneim M Ewedah
AU - Rania Mostafa Abd El Galil
AU - Mahmoud Nour El-Din
AU - Ahmed I Ashmawy
AU - Heba Sabry Ahmed
AU - Azza ElSayed Abd ElFattah Mansy
AU - Ahmed Mohsen Elsaid Hamdan
PY - 2026
DA - 2026/09/30
JO - Pharmaceutics
DO - 10.3390/pharmaceutics18101244
UR - https://europepmc.org/article/MED/42942776
AB - Background: Neratinib (NTB) is a potent pan-HER inhibitor, but its oral bioavailability is limited due to poor aqueous solubility, low permeability, and gastrointestinal toxicity. This study incorporated a bioactive transdermal system by incorporating NTB-loaded nanovesicles of Ocimum basilicum oil (NTB-OOs) into dissolving microneedles of PVA/PVP-propolis. Methods: Ocimum basilicum oil was characterized by gas chromatography-mass spectrometry (GC-MS). NTB-OOs were screened by I-optimal design and evaluated for vesicular properties, stability, release, skin permeation, and cytotoxicity. The optimized vesicles were loaded in propolis microneedles and evaluated mechanically, ex vivo, and in MCF-7 cells and Ehrlich solid carcinoma-bearing mice. Results: GC-MS revealed a volatile profile rich in linalool, methyl jasmonate, and a cyclopenta[g]-2-benzopyran derivative with reported antioxidant and anticancer activities. The optimized NTB-OOs showed a particle size of (198.9 ± 0.98 nm), entrapment efficiency of (88.9 ± 0.45%), PDI of (0.16 ± 0.01), zeta potential of (-23.1 ± 0.35 mV), and six-month stability. The microneedles provided zero-order release (48-50% after 24 h) and ex vivo permeation (~3500 µg/cm²), which were 2.7- and 1.2-fold higher than those of the NTB suspension and NTB-OOs, respectively. NTB-OOs reduced MCF-7 IC₅₀ from 11.1 to 5.1 µg/mL. In vivo, NTB-OOs/propolis microneedles achieved 75.6% tumor inhibition, increased mean survival from 19 to 26.5 days, and raised the T/C ratio to 139.5%. They also induced apoptosis and downregulated the expression of HER-2, EGFR, VEGF-A, and Bcl-2. Conclusions: The multifunctional nanovesicle-propolis microneedle platform improves NTB solubilization, controlled release, dermal delivery, and antitumor efficacy, supporting its potential for minimally invasive localized breast cancer therapy.
SN - 1999-4923
ER -