NLC-Based Sunscreen Formulations with Optimized Proportion of Encapsulated and Free Filters Exhibit Enhanced UVA and UVB Photoprotection.

The topical use of sunscreens is recommended for avoiding the damaging effects of UV radiation. However, improvements are still needed in the existing products to enhance their photoprotection effectiveness and safety. This involves minimizing the use of chemical UV filters while providing enhanced and prolonged photoprotection. This work investigated novel sunscreen formulations and their UV protection effects by encapsulating Uvinul® A, Tinosorb® S, and Uvinul® T150 into nanostructured lipid carriers (NLCs) based on bacuri butter and raspberry seed oil. First, the impact of critical formulation and process parameters on NLCs' particle size was evaluated using a 22 Face Centered Central Composite Design. Then, formulations were evaluated in terms of critical quality factors, in vitro skin permeation, and in vitro and in vivo photoprotection activities. The developed NLCs-containing formulations exhibited appropriate size (122-135 nm), PdI (<0.3), encapsulation efficiency (>90%), and drug content (>80%), which were preserved for at least 90 days under different stability conditions. Moreover, these NLCs-based formulations had equivalent skin permeation to emulsion-based controls, and the addition of NLCs into sunscreen cream bases in the optimum proportion of 20% (w/w) resulted in enhanced UVA and UVB photoprotection levels, despite a 10% reduction in the total filters content. Altogether, these results describe the application of nanoencapsulated organic UV filters in innovative sunscreen formulations to achieve superior photoprotection and cosmeceutical properties.

Nanostructured Lipid Carrier Co-loaded with Doxorubicin and Docosahexaenoic Acid as a Theranostic Agent: Evaluation of Biodistribution and Antitumor Activity in Experimental Model.

PURPOSE: Nanotheranostic platforms, i.e., the combination of both therapeutic and diagnostic agents on a single platform, are emerging as an interesting tool for the personalized cancer medicine. Therefore, the aim of this work was to evaluate the in vivo properties of a Tc-99m-labeled nanostructured lipid carrier (NLC) formulation, co-loaded with doxorubicin (DOX) and docosahexaenoic acid (DHA), for theranostic applications. PROCEDURES: NLC-DHA-DOX were prepared busing the hot melting homogenization method using an emulsification-ultrasound and were radiolabeled with Tc-99m. Biodistribution studies, scintigraphic images, and antitumor activity were performed in 4T1 tumor-bearing mice. RESULTS: NCL was successfully radiolabeled with Tc-99m. Blood clearance showed a relatively long half-life, with blood levels decaying in a biphasic manner (T1/2 α = 38.7 min; T1/2 ß = 516.5 min). The biodistribution profile and scintigraphic images showed higher tumor uptake compared to contralateral muscle in all time-points investigated. Antitumor activity studies showed a substantial tumor growth inhibition ratio for NLC-DHA-DOX formulation. In addition, the formulation showed more favorable toxicity profiles when compared to equivalent doses of free administered drugs, being able to reduce heart and liver damage. CONCLUSIONS: Therefore, NLC-DHA-DOX formulation demonstrated feasibility in breast cancer treatment and diagnosis/monitoring, leading to a new possibility of a theranostic platform.

Solid lipid nanoparticles co-loaded with doxorubicin and α-tocopherol succinate are effective against drug-resistant cancer cells in monolayer and 3-D spheroid cancer cell models.

This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopherol succinate (TS) and to evaluate its potential to overcome drug resistance and to increase antitumoral effect in MCF-7/Adr and NCI/Adr cancer cell lines. The SLN were prepared by a hot homogenization method and characterized for size, zeta potential, entrapment efficiency (EE), and drug loading (DL). The cytotoxicity of SLN or penetration was evaluated in MCF-7/Adr and NCI/adr as a monolayer or spheroid cancer cell model. The SLN showed a size in the range of 74-80nm, negative zeta potential, EE of 99%, and DL of 67mg/g. The SLN co-loaded with Dox and TS showed a stronger cytotoxicity against MCF-7/Adr and NCI/Adr cells. In the monolayer model, the doxorubicin co-localization as a free and encapsulated form was higher for the encapsulated drug in MCF-7/Adr and NCI/adr, suggesting a bypassing of P-glycoprotein bomb efflux. For cancer cell spheroids, the SLN co-loaded with doxorubicin and TS showed a prominent cytotoxicity and a greater penetration of doxorubicin.

α-Tocopherol succinate improves encapsulation and anticancer activity of doxorubicin loaded in solid lipid nanoparticles.

This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopheryl succinate (TS), a succinic acid ester of α-tocopherol that exhibits anticancer actions, evaluating the influence of TS on drug encapsulation efficiency. The SLN were characterized for size, zeta potential, entrapment efficiency (EE), and drug release. Studies of in vitro anticancer activity were also conducted. The EE was significantly improved from 30 ± 1% to 96 ± 2% for SLN without and with TS at 0.4%, respectively. In contrast, a reduction in particle size from 298 ± 1 to 79 ± 1 nm was observed for SLN without and with TS respectively. The doxorubicin release data show that SLN provide a controlled drug release. The in vitro studies showed higher cytotoxicity for doxorubicin-TS-loaded SLN than for free doxorubicin in breast cancer cells. These findings suggest that TS-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer.

Improved pharmacokinetics and enhanced tumor growth inhibition using a nanostructured lipid carrier loaded with doxorubicin and modified with a layer-by-layer polyelectrolyte coating.

A nanostructured lipid carrier (NLC) loaded with doxorubicin (DOX) has been shown to be cytotoxic against the human cancer cell lines A549 and MCF-7/Adr. In attempts to improve formulation characteristics, enhance pharmacokinetics and antitumor effects, we modified the surface of these NLC with an alternating layer-by-layer (LbL) assembly of polycation and polyanion polyelectrolytes and an additional coating with PEG using a simple method of core shell attachment. The formulation had a narrow size distribution, longer residence in the blood, lower accumulation in the liver, higher accumulation in tumors and a significant tumor growth inhibition effect. Thus, NLC-DOX nanopreparations complexes modified by LbL coating have the potential to enhance the anticancer effects of DOX against tumors.

Novel nanostructured lipid carrier co-loaded with doxorubicin and docosahexaenoic acid demonstrates enhanced in vitro activity and overcomes drug resistance in MCF-7/Adr cells.

PURPOSE: To develop a nanostructured lipid carrier (NLC) co-loaded with doxorubicin and docosahexaenoic acid (DHA) and to evaluate its potential to overcome drug resistance and to increase antitumoral effect in MCF-7/Adr cancer cell line. METHODS: The NLC was prepared by a hot homogenization method and characterized for size, zeta potential, entrapment efficiency (EE) and drug loading (DL). Drug release was evaluated by dialysis in complete DMEM, and NLC aggregation was assayed in the presence of serum. The cytotoxicity of formulations, doxorubicin uptake or penetration were evaluated in MCF-7 and MCF-7/Adr as monolayer or spheroid models. RESULTS: The formulation had a size of about 80 nm, negative zeta potential, EE of 99%, DL of 31 mg/g, a controlled drug release in DMEM and no particles aggregation in presence of serum. The NLC loaded with doxorubicin and DHA showed the same activity as free drugs against MCF-7 but a stronger activity against MCF-7/Adr cells. In monolayer model, the doxorubicin uptake as free and encapsulated form was similar in MCF-7 but higher for the encapsulated drug in MCF-7/Adr, suggesting a bypassing of P-glycoprotein bomb efflux. For spheroids, the NLC loaded with doxorubicin and DHA showed a prominent cytotoxicity and a greater penetration of doxorubicin. CONCLUSIONS: These findings suggest that the co-encapsulation of doxorubicin and DHA in NLC enhances the cytotoxicity and overcomes the doxorubicin resistance in MCF-7/Adr.

Recent trends in the use of lipidic nanoparticles as pharmaceutical carriers for cancer therapy and diagnostics.

Lipidic nanoparticles have recently gained attention in cancer research. In this review we are focused on the solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC). They have significant advantages including low toxicity of the lipids and the controlled release of the drugs incorporated into the matrix. The recent trends described here contain functions added to nanoparticles to improve the therapeutic efficacy, such as long-circulation, co-loading of drugs, the combination with RNA/DNA, pH stimulus-sensitive drug release, incorporation of agents for imaging and the attachment of ligands for active targeting. By putting it all together, it may be possible to obtain an ideal multifunctional nanocarrier for cancer therapy. Among the many efforts made so far to obtain one, SLN/NLC should have a place in this search for a combined therapeutic and diagnostic system with dramatically enhanced efficacy in cancer therapy.