Imiquimod-Loaded Nanosystem for Treatment Human Papillomavirus-Induced Lesions

Human papillomavirus (HPV)-associated cervical cancer is the most common cancer among women worldwide. The treatment options are strongly related to increased infertility in women. Imiquimod (IQ) is an imidazoquinoline, which has proven antiviral effects against persistent HPV infection by activatin...

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Bibliographic Details
Published in:Pharmaceutics 2024-06, Vol.16 (7), p.864
Main Authors: Maocha, Izamara, Rosado, Beatriz, Lopes-Nunes, Jéssica, Lopes, Melanie, Rolo, Joana, Pires, Bruno, Gallardo, Eugénia, Palmeira-de-Oliveira, Ana, Martinez-de-Oliveira, José, Palmeira de Oliveira, Rita, Medeiros, Rui, Cruz, Carla
Format: Article
Language:English
Subjects:
Cervical cancer
Cholesterol
Cytokines
DNA aptamer
Drug delivery systems
essential oils
Ethanol
Human papillomavirus
imiquimod
liposomes
Nanoparticles
Oils & fats
vaginal formulation
Womens health
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Summary:Human papillomavirus (HPV)-associated cervical cancer is the most common cancer among women worldwide. The treatment options are strongly related to increased infertility in women. Imiquimod (IQ) is an imidazoquinoline, which has proven antiviral effects against persistent HPV infection by activating immune cells via Toll-like receptors 7/8 when formulated in carriers, like nanogels, for topical use. An effective alternative to conventional therapies is the nanoparticle drug delivery system. We studied lipidic nanoparticles with IQ (Lipo IQ) and functionalized them with a DNA aptamer, AT11 (Lipo IQ AT11), to improve the selectivity for cervical cancer cells combined with the efficacy of essential oils. The formulations showed that the physicochemical properties are adequate for vaginal drug delivery and have antimicrobial activity at higher concentrations (with MIC starting from 0.625%). The final formulations exhibited cytotoxicity in cancer cells, enhanced by essential oils without affecting healthy cells, resulting in less than 10% cell viability in HeLa cells and over 60% in NHDF cells. Essential oils potentiate Lipo IQ's effectiveness, while AT11 increases the selectivity for cervical cancer cells. As suggested by the results of the permeation assay, the formulations were internalized by the cancer cells. Overall, the obtained results suggested that the synergistic effect of the essential oils and the nanosystem potentiate the cytotoxic effect of Lipo IQ and that Lipo IQ AT11 promotes selectivity towards cancer cells.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics16070864