Docetaxel Loaded in Copaiba Oil-Nanostructured Lipid Carriers as a Promising DDS for Breast Cancer Treatment.

Breast cancer is the neoplasia of highest incidence in women worldwide. Docetaxel (DTX), a taxoid used to treat breast cancer, is a BCS-class-IV compound (low oral bioavailability, solubility and intestinal permeability). Nanotechnological strategies can improve chemotherapy effectiveness by promoting sustained release and reducing systemic toxicity. Nanostructured lipid carriers (NLC) encapsulate hydrophobic drugs in their blend-of-lipids matrix, and imperfections prevent drug expulsion during storage. This work describes the preparation, by design of experiments (23 factorial design) of a novel NLC formulation containing copaiba oil (CO) as a functional excipient. The optimized formulation (NLCDTX) showed approximately 100% DTX encapsulation efficiency and was characterized by different techniques (DLS, NTA, TEM/FE-SEM, DSC and XRD) and was stable for 12 months of storage, at 25 °C. Incorporation into the NLC prolonged drug release for 54 h, compared to commercial DTX (10 h). In vitro cytotoxicity tests revealed the antiproliferative effect of CO and NLCDTX, by reducing the cell viability of breast cancer (4T1/MCF-7) and healthy (NIH-3T3) cells more than commercial DTX. NLCDTX thus emerges as a promising drug delivery system of remarkable anticancer effect, (strengthened by CO) and sustained release that, in clinics, may decrease systemic toxicity at lower DTX doses.

Evaluation of miscibility and polymorphism of synthetic and natural lipids for nanostructured lipid carrier (NLC) formulations by Raman mapping and multivariate curve resolution (MCR).

Nanostructured lipid carriers (NLC) belong to youngest lipid-based nanocarrier class and they have gained increasing attention over the last ten years. NLCs are composed of a mixture of solid and liquid lipids, which solubilizes the active pharmaceutical ingredient, stabilized by a surfactant. The miscibility of the lipid excipients and structural changes (polymorphism) play an important role in the stability of the formulation and are not easily predicted in the early pharmaceutical development. Even when the excipients are macroscopically miscible, microscopic heterogeneities can result in phase separation during storage, which is only detected after several months of stability studies. In this sense, this work aimed to evaluate the miscibility and the presence of polymorphism in lipid mixtures containing synthetic (cetyl palmitate, Capryol 90®, Dhaykol 6040 LW®, Precirol ATO5® and myristyl myristate) and natural (beeswax, cocoa and shea butters, copaiba, sweet almond, sesame and coconut oils) excipients using Raman mapping and multivariate curve resolution - alternating least squares (MCR-ALS) method. The results were correlated to the macroscopic stability of the formulations. Chemical maps constructed for each excipient allowed the direct comparison among formulations, using standard deviation of the histograms and the Distributional Homogeneity Index (DHI). Lipid mixtures of cetyl palmitate/Capryol®; cetyl palmitate/Dhaykol®; myristyl myristate/Dhaykol® and myristyl myristate/coconut oil presented a single histogram distribution and were stable. The sample with Precirol®/Capryol® was not stable, although the histogram distribution was narrower than the samples with cetyl palmitate, indicating that miscibility was not the factor responsible for the instability. Structural changes before and after melting were identified for cocoa butter and shea butter, but not in the beeswax. Beeswax + copaiba oil sample was very homogenous, without polymorphism and stable over 6 months. Shea butter was also homogeneous and, in spite of the polymorphism, was stable. Formulations with cocoa butter presented a wider histogram distribution and were unstable. This paper showed that, besides the miscibility evaluation, Raman imaging could also identify the polymorphism of the lipids, two major issues in lipid-based formulation development that could help guide the developer understand the stability of the NLC formulations.

Non-destructive fraud detection in rosehip oil by MIR spectroscopy and chemometrics.

Rosehip oil (Rosa eglanteria L.) is an important oil in the food, pharmaceutical and cosmetic industries. However, due to its high added value, it is liable to adulteration with other cheaper or lower quality oils. With this perspective, this work provides a new simple, fast and accurate methodology using mid-infrared (MIR) spectroscopy and partial least squares discriminant analysis (PLS-DA) as a means to discriminate authentic rosehip oil from adulterated rosehip oil containing soybean, corn and sunflower oils in different proportions. The model showed excellent sensitivity and specificity with 100% correct classification. Therefore, the developed methodology is a viable alternative for use in the laboratory and industry for standard quality analysis of rosehip oil since it is fast, accurate and non-destructive.

Extra virgin (EV) and ordinary (ON) olive oils: distinction and detection of adulteration (EV with ON) as determined by direct infusion electrospray ionization mass spectrometry and chemometric approaches.

Extra virgin (EV), the finest and most expensive among all the olive oil grades, is often adulterated by the cheapest and lowest quality ordinary (ON) olive oil. A new methodology is described herein that provides a simple, rapid, and accurate way not only to detect such type of adulteration, but also to distinguish between these olive oil grades (EV and ON). This approach is based on the application of direct infusion electrospray ionization mass spectrometry in the positive ion mode, ESI(+)-MS, followed by the treatment of the MS data via exploratory statistical approaches, PCA (principal component analysis) and HCA (hierarchical clustering analysis). Ten distinct brands of each EV and ON olive oil, acquired at local stores, were analyzed by ESI(+)-MS and the results from HCA and PCA clearly indicated the formation of two distinct groups related to these two categories. For the adulteration study, one brand of each olive oil grade (EV and ON) was selected. The counterfeit samples (a total of 20) were then prepared by adding assorted proportions, from 1 to 20% w/w, with increments of 1% w/w, of the ON to the EV olive oil. The PCA and HCA methodologies, applied to the ESI(+)-MS data from the counterfeit (20) and authentic (10) EV samples, were able to readily detect adulteration, even at levels as low as 1% w/w.