Perspectives of topical formulations for melasma.

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.

A review of alternative methods to the use of animals in safety evaluation of cosmetics.

Alternative methods to the use of animals in research have been a global trend, mainly after the publication of the 3R's principle (Replacement, Reduction, and Refinement), proposed by Russel and Burch. In the cosmetic sector, safety and efficacy assessments using animals have generated controversial debates. For this reason, in vitro research techniques are widely used to assess acute toxicity; corrosivity and irritation; skin sensitization; dermal and percutaneous absorption; repeated dose toxicity; reproductive toxicity; mutagenicity and genotoxicity; carcinogenicity; toxicokinetic studies; photo-induced toxicity; and human data. Although there are many methodologies described, validated, and widely used in the cosmetic area, the evaluation of the safety of cosmetic ingredients and products is still an expanding field. It needs global collaboration among regulatory agencies, universities, and industry, to meet several unmet needs in the fields of sensitization, carcinogenicity, systemic action, among other issues involving safety of users of cosmetic products. This review article will cover the currently most relevant in vitro models regarding irritation, corrosion, sensitization, mutagenicity, genotoxicity, and phototoxicity, to help to choose the most appropriate test for evaluating the safety and toxicity of cosmetic ingredients and products.

A review of alternative methods to the use of animals in safety evaluation of cosmetics

ABSTRACT Alternative methods to the use of animals in research have been a global trend, mainly after the publication of the 3R's principle (Replacement, Reduction, and Refinement), proposed by Russel and Burch. In the cosmetic sector, safety and efficacy assessments using animals have generated controversial debates. For this reason, in vitro research techniques are widely used to assess acute toxicity; corrosivity and irritation; skin sensitization; dermal and percutaneous absorption; repeated dose toxicity; reproductive toxicity; mutagenicity and genotoxicity; carcinogenicity; toxicokinetic studies; photo-induced toxicity; and human data. Although there are many methodologies described, validated, and widely used in the cosmetic area, the evaluation of the safety of cosmetic ingredients and products is still an expanding field. It needs global collaboration among regulatory agencies, universities, and industry, to meet several unmet needs in the fields of sensitization, carcinogenicity, systemic action, among other issues involving safety of users of cosmetic products. This review article will cover the currently most relevant in vitro models regarding irritation, corrosion, sensitization, mutagenicity, genotoxicity, and phototoxicity, to help to choose the most appropriate test for evaluating the safety and toxicity of cosmetic ingredients and products.

Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration.

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.

Solid lipid nanoparticles optimized by 22 factorial design for skin administration: Cytotoxicity in NIH3T3 fibroblasts.

The present study focuses on the characterization of the cytotoxic profile on NIH3T3 mouse embryonic fibroblasts of solid lipid nanoparticles (SLN) optimized by a 22 full factorial design for skin administration. To build up the surface response charts, a design of experiments (DoE) based on 2 independent variables was used to obtain an optimized formulation. The effect of the composition of lipid and water phases on the mean particle size (z-AVE), polydispersity index (PdI) and zeta potential (ZP) was studied. The developed formulations were composed of 5.0% of lipid phase (stearic acid (SA), behenic alcohol (BA) or a blend of SA:BA (1:1)) and 4.7% of surfactants (soybean phosphatidylcholine and poloxamer 407). In vitro cytotoxicity using NIH3T3 fibroblasts was performed by MTT reduction assay. This factorial design study has proven to be a useful tool in optimizing SLN (z-AVE ∼ 200 nm), which were shown to be non-cytotoxic. The present results highlight the benefit of applying statistical designs in the preparation and optimization of SLN formulations.

Comparative Study of Glyceryl Behenate or Polyoxyethylene 40 Stearate-Based Lipid Carriers for Trans-Resveratrol Delivery: Development, Characterization and Evaluation of the In Vitro Tyrosinase Inhibition.

Trans-resveratrol (RSV) is a natural compound with several properties, such as the ability to inhibit the tyrosinase enzyme, with potential application as a skin-lightning agent and for the treatment of skin disorders associated with hyperpigmentation and melanogenesis. However, the drug faces several drawbacks which altogether limit its therapeutic application. Thus, drug loading into nanocarriers emerge as an alternative to circumvent these problems. Herein, nanostructured lipid carriers (NLCs) have been employed for RSV encapsulation, with comparison of two different lipids, glyceryl behenate (more hydrophobic), and polyoxyethylene 40 (PEG 40) stearate. PEG 40 stearate-containing NLCs presented smaller particle size and polydispersity compared with glyceryl behenate, attributed to better emulsification and nanoparticle formation, resulting in higher RSV encapsulation efficiency. Drug was loaded in both carriers as a molecular dispersion. Furthermore, the formulations had very low RSV release, which occurred due to the crystallinity degree of lipid matrix, in accordance with the DSC data. Moreover, RSV cytotoxicity against L-929 cells was not increased when loaded into nanocarriers. Interestingly, RSV-loaded formulation prepared with PEG-40 stearate resulted on greater tyrosinase inhibition than RSV solution and formulation containing glyceryl behenate, equivalent to 1.31 and 1.83 times higher, respectively, demonstrating that the incorporation of RSV into NLC allowed an enhanced tyrosinase inhibitory activity. Overall, the results obtained herein evidence potential for future in vivo evaluation of RSV-loaded NLCs.

Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review.

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.