The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo.

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. FROM THE CLINICAL EDITOR: Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect.

DACHPt-Loaded Unimolecular Micelles Based on Hydrophilic Dendritic Block Copolymers for Enhanced Therapy of Lung Cancer.

Combining sufficient stability during circulation and desirable drug release is still a great challenge for the clinical applications of nanocarriers. To satisfy this demand, we developed a novel unimolecular micelle (UM) to deliver the antitumor agent 1,2-diaminocyclohexane-platinum(II) (DACHPt) for enhanced therapy of lung cancer. This DACHPt-loaded UM (UM/DACHPt) was formed through chelate complexation between DACHPt and a hydrophilic and biodegradable dendritic block copolymer poly(amidoamine)-polyglutamic acid-b-polyethylene glycol (PAM-PGlu-b-PEG), which was composed of generation 3 PAMAM (PAMAM-G3), polyglutamic acid, and long-circulating polymer PEG. This UM/DACHPt displayed robust stability and would effectively inhibit the undesired release under physiological condition, thus exhibiting much longer in vivo half-life than diblock copolymer micelles. With significant in vitro cell cytotoxicity to A549 lung cancer cells, this UM/DACHPt demonstrated efficient antitumor efficacy on an A549 xenograft tumor model with negligible tissue cytotocxity. Therefore, this UM/DACHPt provides a promising new strategy for lung cancer therapy.

Hepatitis C virus E2 protein encapsulation into poly d, l-lactic-co-glycolide microspheres could induce mice cytotoxic T-cell response.

Hepatitis C virus (HCV) is known to cause hepatitis and hepatocellular carcinoma. E2 envelope glycoprotein of HCV type (HCV-E2) has been reported to bind human host cells and is a major target for developing anti-HCV vaccines. However, the therapeutic vaccine for infected patients still needs further development. The vaccine aims to provide cytotoxic T-cells to eliminate infected cells and hepatocellular carcinoma. Currently, there is no effective HCV therapeutic vaccine because most chronically infected patients rarely generate cytotoxic T-cells, even though they have high levels of neutralizing antibodies. Therefore, the adjuvant must be applied to enhance the efficacy of the therapeutic vaccine. In this study, we constructed HCV1b-E2 recombinant protein, a truncated form of peptide, to combine with an effective vaccine adjuvant and delivery system by using poly d,l-lactic-co-glycolide (PLGA) microspheres. HCV1b-E2 protein was effectively encapsulated into PLGA microspheres (HCV1b-E2-PLGA) as a strategy to deliver an insoluble form of HCV1b-E2 protein. The size and shape of PLGA microspheres were generated properly to carry an insoluble form of viral peptide in vivo. The encapsulated viral protein was slowly and continuously released from PLGA microspheres, which indicated the property of the adjuvant. HCV1b-E2-PLGA can trigger a cell-mediated immune response by inducing an expression of mice CD8+ T-cells. Our results demonstrated that HCV1b-E2-PLGA-immunized mice have a significantly increased CD8+ T-cell number, whereas HCV1b-E2-immunized mice have a lower number of CD8+ T-cells. Moreover, HCV1b-E2-PLGA could induce a specific antibody to viral protein, and the immune cells could secrete IFN-γ, which is a significant cytokine for viral response. Thus, HCV1b-E2-PLGA is shown to have adjuvant property and efficacy in the murine model, which is a good strategy to develop HCV prophylactic and therapeutic vaccines.