Marilene Estanqueiro

Nanotechnological carriers for cancer chemotherapy: the state of the art.

Cancer is a term used for a heterogeneous group of malignant diseases in which abnormal cells divide without control and are able to invade other tissues, resulting in metastasis. According to the last data of World Health Organization the incidence and mortality rates of cancer are high and tend to increase. Chemotherapy is usually used in cancer treatments, but due to the lack of specificity of drugs, is associated to various and damaging side effects that have a severe impact on patients quality of life. Nanotechnology is actually an important area of interest in science and technology, which has been extensively explored during the last decade, particularly in the development of carriers for cytotoxic drugs. These carriers include vesicular and particulate systems such as liposomes, niosomes, transfersomes, ethosomes, micelles, dendrimers, and polymeric, protein and lipid nanoparticles. Polymer-drug conjugates and antibody-drug conjugates have also been studied. The present review is an attempt to contemplate the studied nanocarriers in the field of anticancer drugs delivery, their advantages and disadvantages and future perspectives.

Comparison between sensory and instrumental characterization of topical formulations: impact of thickening agents.

Sensorial properties of cutaneous formulations are important in determining their acceptability by consumers. However, sensorial analysis is time‐consuming and requires an available panel of trained assessors. Thus, this article aimed to study the impact of thickening agents on mechanical properties of creams and investigate how these measurements could correlate the sensory attributes using a combined instrumental–sensorial approach.

Characterization, sensorial evaluation and moisturizing efficacy of nanolipidgel formulations.

Nanostructured lipid carriers (NLC) have been widely studied for cosmetic and dermatological applications due to their favourable properties that include the formation of an occlusive film on the skin surface that reduces the transepidermal water loss (TEWL) and increase in water content in the skin which improves the appearance on healthy human skin and reduces symptoms of some skin disorders like eczema.

Development and characterization of mucoadhesive buccal gels containing lipid nanoparticles of ibuprofen

The lipid nanoparticles, namely Nanostructured Lipid Carriers (NLC), as drug delivery systems have been investigated for several years. One of the delivery routes for which these carriers can be applied is buccal administration. However, the liquid dispersions of lipid nanoparticles can be rapidly removed from oral cavity by saliva. Thus, the development of a system that allows increased retention time on the mucosa is necessary. For this reason, the development of mucoadhesive preparations for buccal administration of lipid nanoparticles becomes important. Hydrogels prepared with mucoadhesive polymers (Carbopol® 980 and polycarbophil) constitute a promising option. The aim of this work was to develop mucoadhesive buccal hydrogels with NLC, using ibuprofen as a model drug. The obtained results showed that the developed NLC dispersions presented particles in the nanometric size range, with low polydispersity index values and efficient ability for the entrapment of the model drug. Moreover, the incorporation of NLC in hydrogels of mucoadhesive polymers resulted in preparations with desirable rheological features as well as texture (firmness and adhesiveness) and mucoadhesive properties, which could benefit the therapeutic efficacy, by increasing the residence time and easiness for topical application in the buccal mucosa. Additionally, the developed preparations exhibited sustained drug release as intended for these systems.

The role of liposomes and lipid nanoparticles in the skin hydration

Cosmetics are much more than beauty products and the maintenance of skin hydration could be considered the most important step to getting healthy skin. The hydration could be supplied to the skin internally by ingestion of water, or externally, by applying cosmetic formulations containing moisturizing ingredients and/or components that reduce transepidermal water loss (TEWL). In recent years, liposomes and lipid nanoparticles (solid lipid nanoparticles and nanostructured lipid carriers) have received a great deal of attention in the field of pharmaceutical and cosmetic research. These nanosystems have proved to be very advantageous for skin applications and numerous studies were carried out with the aim of encapsulating numerous cosmetic ingredients in liposomes and lipid nanoparticles. Additionally, when applied on the skin, these systems form a transparent film that reduces the TEWL and increases hydration. The main objectives of this chapter include: presenting the importance of skin hydration to maintain health and the mechanisms that could be involved, exemplifying with moisturizing ingredients commonly used in cosmetics; discussing the application of lipid-based nanocarriers, referring to the advantages of these systems and the ingredients commonly used with benefits to skin; showing and discussing examples of some interesting studies performed in this field; and presenting some examples of marketed cosmetic formulations containing liposomes and lipid nanoparticles.

Characterization and stability studies of emulsion systems containing pumice

Emulsions are the most common form of skin care products. However, these systems may exhibit some instability. Therefore, when developing emulsions for topical application it is interesting to verify whether they have suitable physical and mechanical characteristics and further assess their stability. The aim of this work was to study the stability of emulsion systems, which varied in the proportion of the emulsifying agent cetearyl alcohol (and) sodium lauryl sulfate (and) sodium cetearyl sulfate (LSX), the nature of the oily phase (decyl oleate, cyclomethicone or dimethicone) and the presence or absence of pumice (5% w/w). While maintaining the samples at room temperature, rheology studies, texture analysis and microscopic observation of formulations with and without pumice were performed. Samples were also submitted to an accelerated stability study by centrifugation and to a thermal stress test. Through the testing, it was found that the amount of emulsifying agent affects the consistency and textural properties such as firmness and adhesiveness. So, formulations containing LSX (5% w/w) and decyl oleate or dimethicone as oily phase had a better consistency and remained stable with time, so exhibited the best features to be used for skin care products.

Delivering miRNA modulators for cancer treatment

Abstract Cancer is a disease that involves dynamic changes in the genome resulting from genetic damage, particularly in oncogenes, tumor-suppressor genes, genes involved in programmed cell death and genes involved in DNA repair. Micro-RNAs (miRNAs or miRs) are a class of noncoding RNAs which can regulate gene expression at a post-transcriptional level. Several miRNAs have been shown to regulate cellular processes that are involved in the hallmarks of cancer, such as apoptosis, proliferation or metastasis, being implicated not only in cancer progression and malignancy but also in cancer resistance to therapy. Antimicro-RNAs, also called antago-miRs or anti-miRs, are inhibitory oligonucleotides with complementary nucleotide sequences to specific miRNAs, capable of specifically targeting those miRNAs intracellularly, thereby decreasing their intracellular levels. Thus, anti-miRs may represent a promising therapeutic strategy for silencing specific miRNAs in cancer. Indeed, both miRNA mimics and anti-miRs have been shown to have potential therapeutic application in cancer, for example, by modifying the expression levels of genes involved in the hallmarks of cancer. However, the in vivo efficacy of these molecules may be compromised when administered free into the bloodstream, since they are very labile and can be rapidly degraded by nucleases before reaching the site of action. The use of viral vectors as carriers of these molecules has been described. However, due to their possible lack of safety, the scientific community has been focusing efforts on the development of nonviral vectors. Conversely, nanotechnology offers drug delivery systems which can accumulate in tumors by passive and active targeting, being suitable for cancer treatment. It is well established that nanotechnological carriers injected into the bloodstream may accumulate selectively in tumors by passive targeting due to the enhanced permeability and retention (impaired lymphatic function), generally known as the EPR effect. Therefore, nanotechnological approaches have been developed to deliver miRNA modulators to cancer cells. This chapter aims to first describe the role of miRNAs in cancer pathology and its response to therapy, then to report the potential therapeutic role of miRNA modulators in cancer treatment, and finally to explore the applicability of different nanocarriers in the delivery of these molecules.

Lipid-Based Nanocarriers in Cancer Therapy

Cancer is a group of malignant diseases in which mutated cells divide wildly and have invasive capacity, resulting in metastasis formation. Considering the last published data by the World Health Organization, the incidence and mortality rates of cancer are high, and tend to increase. Conventional anticancer drugs have a lack of specificity for tumor cells, leading to systemic toxicity with consequent adverse effects, limiting the maximum dose of drug that can be administered. At the present time, nanotechnology represents an area of interest in science and technology, extensively explored, particularly in the field of drug delivery, including cytotoxic drugs, with significant improvements. Liposomes, discovered by chance in the 1960s, rapidly passed from a simple scientific curiosity to important drug delivery systems. Liposomes carrying different anticancer drugs have been widely studied, with notorious advances, resulting in the market introduction of some of them. In the early 1990s, lipid nanoparticles were developed as an alternative that was more stable, compared to other drug delivery systems, and consequently they have also been studied in the context of improving cancer chemotherapy. The main topics that will be addressed in this chapter include: a brief description of cancer pathogenesis and treatments; an approach about the nanocarrier properties that make these systems advantageous for drug delivery; a brief description of liposomes and lipid nanoparticles, including their production methods; a critical revision of the research work developed under the application of liposomes and lipid nanoparticles in cytotoxic drug delivery.

Use of solid dispersions to increase stability of dithranol in topical formulations

Este trabalho teve como objetivo aumentar a estabalidade do ditranol atraves da preparacao de dispersoes solidas (DS). Prepararam-se duas DS diferentes em proporcao de 1:9 de ditranol/excipiente: em uma das DS utilizou-se beenato de glicerila como excipiente e na outra se utilizou mistura de oleo de argan com acido estearico (razao 1:8). Posteriormente, efetuou-se a incorporacao de ditranol puro e das DS contendo este farmaco num creme hidrofilo ou oleo-agua (O/A) e em pomada hidrofoba, na proporcao 1:10 (farmaco ou respetivas DS/base dermatologica). As propriedades fisicas e mecânicas das formulacoes semissolidas incorporando farmaco ou as respetivas DS previamente desenvolvidas, foram avaliadas atraves da analise do comportamento reologico e das propriedades de textura. Para avaliar a estabilidade, os parâmetros do espaco de cor L*a*b* das DS e das formulacoes semissolidas e o pH das preparacoes hidrofilas foram determinados em periodos de tempo definidos, durante um mes para cada amostra armazenada sob diferentes condicoes, especificamente, exposicao a luz (a temperatura ambiente), protegidas da luz a temperatura elevada (37 °C) e protegidas da luz (temperatura ambiente). Embora tenham apresentado valores de firmeza e de adesividade mais elevados, as pomadas hidrofobas apresentaram melhores caracteristicas reologicas do que os cremes oleo-agua. Alem disso, as pomadas hidrofobas tambem apresentaram melhor estabilidade, com pequenas alteracoes nos parâmetros do espaco de cor L*a*b*. Os resultados deste trabalho permitiram concluir que as DS desenvolvidas contribuiram para o aumento da estabilidade do ditranol.