New pectin-based hydrogel containing imiquimod-loaded polymeric nanocapsules for melanoma treatment
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ORIGINAL ARTICLE
New pectin-based hydrogel containing imiquimod-loaded polymeric nanocapsules for melanoma treatment R. P. Gazzi 1 & L. A. Frank 1 & G. Onzi 1 & A. R. Pohlmann 1,2 & Silvia S. Guterres 1,3
# Controlled Release Society 2020
Abstract We developed a pectin-based hydrogel containing nanocapsules as a new strategy for melanoma treatment. Our first objective was to evaluate the nanoencapsulation effect of imiquimod on melanoma. Imiquimod-loaded polymeric nanocapsules (NCimiq) showed significant time-dependent decrease in cell viability after treatment at 3 μmol L−1 (79% viable cells in 24 h and 55% in 72 h), which was not observed in cells treated with the solution of the drug (IMIQ) (99% viable cells in 24 h and 91% in 72 h). The second objective was to develop the hydrogel containing the drug-loaded nanocapsules (PEC-NCimiq). In vitro release study showed that 63% of imiquimod was released from the pectin-based hydrogel containing the drug (PEC-imiq) after 2 h, while 60% of the drug was released from PEC-NCimiq after 8 h. In the permeation study, 2.5 μg of imiquimod permeated the skin within 8 h after the initial contact of PEC-NCimiq, whereas only 2.1 μg of drug permeated after 12 h of contact when PEC-imiq was assayed. Pectin-based hydrogels enabled the drug penetration in all skin layers, especially the dermis (PEC-NCimiq = 6.8 μg and PEC-imiq = 4.3 μg). In the adhesion study, PEC-NCimiq showed the highest adhesiveness (42% removed from the skin) in comparison to PEC-imiq (71% removed from the skin). In conclusion, the nanoencapsulation provided a higher cytotoxic effect of imiquimod in SK-MEL-28, and the incorporation of the drug-loaded nanocapsules in pectin-based hydrogel showed higher adhesiveness and deeper penetration of the drug into the skin. Keywords Pectin hydrogel . Polymeric nanocapsules . Imiquimod . Skin permeation . Skin adhesiveness . Melanoma
Introduction Skin cancer is one of the most common human malignancies, with high worldwide incidence rate, being divided in two types, non-melanoma and melanoma [1]. Non-melanoma tumors are derived manly from basal and squamous cells [2]. The treatment for this type of cancer can be by surgical removal, radiotherapy, or topical treatment, according to the severity [1]. The basal cell carcinoma, which is a slow
* Silvia S. Guterres [email protected] 1
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
2
Departamento de QuímicaOrgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil
3
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752/405 CEP, Porto Alegre, RS 90610-000, Brazil
growing tumor that rarely metastasizes [1], is the most common representative in this group. On the other hand, the melanoma type is derived from melanocytes and, despite being less incident, is the most aggressive and deadly type [3]. The treatment options for this type of cancer include chemoth
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