pH-temperature dual-sensitive nucleolipid-containing stealth liposomes anchored with PEGylated AuNPs for triggering delivery of doxorubicin.

Liposomes (Lip) are useful nanocarriers for drug delivery and cancer nanomedicine because of their ability to efficiently encapsulate drugs with different physical and chemical properties. The pH gradient between normal and tumoral tissues, and their rapid metabolism that induces hyperthermia encourage the development of pH- and thermo-sensitive Lip for delivering anticancer drugs. Nucleolipids have been studied as scaffolding material to prepare Lip, mainly for cancer therapy. Herein, we report for the first time the use of 1,2-dipalmitoyl-sn-glycero-3-(cytidine diphosphate) (DG-CDP) to develop pH/thermo-sensitive nucleolipid-containing stealth Lip stabilized by combination with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol, anchored with NH2-PEGylated gold nanoparticles (PEG-AuNPs, 15 nm) for triggering delivery of doxorubicin (Dox). The optimal composition of DPPC, DG-CDP and cholesterol (94:3:3) was established by Langmuir isotherms. Unloaded and Dox-loaded Lip and AuNPs-Lip exhibited nano-scale sizes (415-650 nm), acceptable polydispersity indexes (<0.33), spherical shapes, and negative Z-potential (-23 to -6.6 mV) due to the phosphate groups of DG-CDP, which allowed the anchoring with positively charged AuNPs. High EE% were achieved (>78%) and although efficient control in the Dox release towards different receptor media was observed, the release of Dox from PEG-AuNPs-Lip-Dox was significantly triggered at acidic pH and hyperthermia conditions, demonstrating its responsiveness to both stimuli. Dox-loaded Lip showed high cytotoxic activity against MDA-MB-231 breast cancer cells and SK-OV-3 ovarian cancer cells, suggesting that Dox was released from these nanocarriers over time. Overall, the liposomal formulations showed promising properties as stimuli-responsive nanocarriers for cancer nanomedicine, with prospects for hyperthermia therapy.

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice.

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation.