Search

Drug discovery has faced many challenges, and the diversity of natural products offers a huge number of opportunities for new drug findings. Most of the potential candidates result from plants since plants have several and interesting biological activities. However, the in vivo efficacy of such candidates is frequently limited due to their low absorption. Thus, enhancing the bioavailability of natural products through the improvement of their pharmacokinetic and biodistribution features, as well as their targeting efficacy, is a crucial step in the development of new therapeutic strategies.

Background: The delivery of drugs or actives through the skin provides a convenient route of administration because it is noninvasive and can typically be self-administered. In skin delivery, different strategies have been developed to enhance the rate and extent of drug transport across the skin. These strategies consist in particulate carriers such as nanoparticles generally made of polymers and lipids where some advantages are solubility improvement of poorly water-soluble drugs, increase of skin permeation through different mechanisms, and ability to modify drug pharmacokinetics. Besides polymeric- and lipidic-, metallic-based nanoparticles like silver nanoparticles are recently used as nanocarriers for skin delivery due to their strong and broad-spectrum antimicrobial characteristics. All encapsulant materials (polymers, lipids, and metals) and solvents used in the drug delivery are approved by Food and Drug Administration (FDA) and European Medicines Agency (EMA) (as biocompatible and biodegradable materials). Major advances: In this chapter, a compilation of the type and the therapeutic implications of nanotechnology applied to the skin in pharmaceutical area as well as safety issues, ecotoxicity concerns, and regulatory framework of different nanoparticles for skin delivery over the last 40 years was described.

Pancreatic cancer is one of the most lethal cancers, with an extremely poor prognosis. The development of more effective therapies is thus imperative. Natural origin compounds isolated from Plectranthus genus, such as parvifloron D (PvD), have cytotoxic and antiproliferative activity against human tumour cells. However, PvD is a very low water-soluble compound, being nanotechnology a promising alternative strategy to solve this problem. Therefore, the aim of this study was to optimize a nanosystem for preferential delivery of PvD to pancreatic tumour cells. Albumin nanoparticles (BSA NPs) were produced through a desolvation method. Glucose cross-linking and bioactive functionalization profiles of BSA platform were elucidated and analysed using static lattice atomistic simulations in vacuum. Using the optimized methodology, PvD was encapsulated (yield higher than 80%) while NPs were characterized in terms of size (100&ndash, 400 nm) and morphology. Importantly, to achieve a preferential targeting to pancreatic cancer cells, erlotinib and cetuximab were attached to the PvD-loaded nanoparticle surface, and their antiproliferative effects were evaluated in BxPC3 and Panc-1 cell lines. Erlotinib conjugated NPs presented the highest antiproliferative effect toward pancreatic tumour cells. Accordingly, cell cycle analysis of the BxPC3 cell line showed marked accumulation of tumour cells in G1-phase and cell cycle arrest promoted by NPs. As a result, erlotinib conjugated PvD-loaded BSA NPs must be considered a suitable and promising carrier to deliver PvD at the tumour site, improving the treatment of pancreatic cancer.

Pancreatic cancer is the eighth leading cause of cancer death worldwide. For this reason, the development of more effective therapies is a major concern for the scientific community. Accordingly, plants belonging to Plectranthus genus and their isolated compounds, such as Parvifloron D, were found to have cytotoxic and antiproliferative activities. However, Parvifloron D is a very low water-soluble compound. Thus, nanotechnology can be a promising delivery system to enhance drug solubility and targeted delivery. The extraction of Parvifloron D from P. ecklonii was optimized through an acetone ultrasound-assisted method and isolated by Flash-Dry Column Chromatography. Then, its antiproliferative effect was selectivity evaluated against different tumor cell lines (IC50 of 0.15 &plusmn, 0.05 &mu, M, 11.9 &plusmn, 0.7 &mu, M, 21.6 &plusmn, 0.5, 34.3 &plusmn, 4.1 &mu, M, 35.1 &plusmn, 2.2 &mu, M and 32.1 &plusmn, 4.3 &mu, M for BxPC3, PANC-1, Ins1-E, MCF-7, HaCat and Caco-2, respectively). To obtain an optimized stable Parvifloron D pharmaceutical dosage form, albumin nanoparticles were produced through a desolvation method (yield of encapsulation of 91.2%) and characterized in terms of size (165 nm, PI 0.11), zeta potential (&minus, 7.88 mV) and morphology. In conclusion, Parvifloron D can be efficiently obtained from P. ecklonii and it has shown selective cytotoxicity to pancreatic cell lines. Parvifloron D nanoencapsulation can be considered as a possible efficient alternative approach in the treatment of pancreatic cancer.