Versatile protamine nanocapsules to restore miR-145 levels and interfere tumor growth in colorectal cancer cells.

MicroRNAs (miRNAs) play a key role on gene expression regulation contributing to cell homeostasis, and they are highly dysregulated in cancer. Consequently, miRNA-based therapies are an attractive approach to develop novel anticancer strategies. The main objective of this work was to explore the full potential of protamine nanocapsules (Pr NCs) to develop an anticancer therapy based on the restoration of oncosuppressor miR-145, downregulated in colorectal cancer cells. The composition of Pr NCs was defined based on the selection of surfactants, and protamine that would enable an efficient association and intracellular delivery of miRNA mimics according to the layer-by-layer approach, and the encapsulation of curcumin within the oily core. After exposure of colorectal cancer cells with (i) miR-145 and (ii) curcumin-loaded Pr NCs, a strong increase in the intracellular levels of miR-145, which translated into a decreased cell proliferation rate and migration capacity of the treated cells, was observed. The potential of exploiting Pr NCs for the co-delivery of both biomolecules, miRNAs and curcumin, has also been proved. All together, here we evaluate the possibility to use Pr NCs to efficiently increase the intracellular levels of the oncosuppressor miR-145.

Polymeric nanocapsules: a potential new therapy for corneal wound healing.

Corneal injuries are one of the most frequently observed ocular diseases, leading to permanent damage and impaired vision if they are not treated properly. In this sense, adequate wound healing after injury is critical for keeping the integrity and structure of the cornea. The goal of this work was to assess the potential of polymeric nanocapsules, either unloaded or loaded with cyclosporine A or vitamin A, alone or in combination with mitomycin C, for the treatment of corneal injuries induced by photorefractive keratectomy surgery. The biopolymers selected for the formation of the nanocapsules were polyarginine and protamine, which are known for their penetration enhancement effect. The results showed that, following topical instillation to a mouse model of corneal injury, all the nanocapsule formulations, either unloaded or loaded with cyclosporine A or vitamin A, were able to stimulate corneal wound healing. In addition, the healing rate observed for the combination of unloaded protamine nanocapsules with mitomycin C was comparable to the one observed for the positive control Cacicol®, a biopolymer known as a corneal wound healing enhancer. Regarding the corneal opacity, the initial grade of corneal haze (>3) induced by the photorefractive keratectomy was more rapidly reduced in the case of the positive control, Cacicol®, than in corneas treated with the nanocapsules. In conclusion, this work shows that drug-free arginine-rich (polyarginine, protamine) nanocapsules exhibit a positive behavior with regard to their potential use for corneal wound healing.

A comparative study of curcumin-loaded lipid-based nanocarriers in the treatment of inflammatory bowel disease.

Selective drug delivery to inflamed tissues is of widespread interest for the treatment of inflammatory bowel disease (IBD). Because a lack of physiological lipids has been described in patients suffering IBD, and some lipids present immunomodulatory properties, we hypothesize that the combination of lipids and anti-inflammatory drugs together within a nanocarrier may be a valuable strategy for overcoming IBD. In the present study, we investigated and compared the in vitro and in vivo efficacy of three lipid-based nanocarriers containing curcumin (CC) as an anti-inflammatory drug for treating IBD in a murine DSS-induced colitis model. These nanocarriers included self-nanoemulsifying drug delivery systems (SNEDDS), nanostructured lipid carriers (NLC) and lipid core-shell protamine nanocapsules (NC). In vitro, a 30-fold higher CC permeability across Caco-2 cell monolayers was obtained using NC compared to SNEDDS (NC>SNEDDS>NLC and CC suspension). The CC SNEDDS and CC NLC but not the CC NC or CC suspension significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo, only CC NLC were able to significantly decrease neutrophil infiltration and TNF-α secretion and, thus, colonic inflammation. Our results show that a higher CC permeability does not correlate with a higher efficacy in IBD treatment, which suggests that lipidic nanocarriers exhibiting increased CC retention at the intestinal site, rather than increased CC permeability are efficient treatments of IBD.