RESUMO
Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS's limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (-37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy.
RESUMO
While research on substance use disorder (SUD) treatment among justice-involved populations has grown in recent years, the majority of corrections-based SUD studies have predominantly included incarcerated men or men on community supervision. This review 1) highlights special considerations for incarcerated women that may serve as facilitating factors or barriers to SUD treatment; 2) describes selected evidence-based practices for women along the cascade of care for SUD including screening and assessment, treatment and intervention strategies, and referral to services during community re-entry; and 3) discusses conclusions and implications for SUD treatment for incarcerated women.
RESUMO
Diethyldithiocarbamate Copper II (DDC-Cu) has shown potent anticancer activity against a wide range of cancer cells, but further investigations are hindered by its practical insolubility in water. In this study, inclusion complexes of DDC-Cu with hydroxypropyl beta-cyclodextrin (HP) or sulfobutyl ether beta-cyclodextrin (SBE) were prepared and investigated as an approach to enhance the apparent solubility of DDC-Cu. Formulations were prepared by simple mixing of DDC-Cu with both cyclodextrin (CDs) at room temperature. Phase solubility assessments of the resulting solutions were performed. DDC-Cu CD solutions were freeze-dried for further characterisations by DSC, thermogravimetric analysis (TGA) and FT-IR. Stability and cytotoxicity studies were also performed to investigate the maintenance of DDC-Cu anticancer activity. The phase solubility profile deviated positively from the linearity (Ap type) showing significant solubility enhancement of the DDC-Cu in both CD solutions (approximately 4 mg/mL at 20% w/w CD solutions). The DSC and TGA analysis confirmed the solid solution status of DDC-Cu in CD. The resulting solutions of DDC-Cu were stable for 28 days and conveyed the anticancer activity of DDC-Cu on chemoresistant triple negative breast cancer cell lines, with IC50 values less than 200 nM. Overall, cyclodextrin DDC-Cu complexes offer a great potential for anticancer applications, as evidenced by their very positive effects against chemoresistant triple negative breast cancer cells.
RESUMO
R-Models are an approach to capturing notions of assistance and abstraction in reproductive systems, based on labelled transition systems and Gibson's theory of affordances. R-Models incorporate a labelled transition system that describes how a reproductive system changes over the course of reproduction. The actors in the system are represented by a set of entities together with a relation describing the states in which those entities are present, and an affordance-modelling function mapping actions to sets of entities which enable those actions to be performed. We show how R-models can be classified based on whether the reproducer is assisted or unassisted in reproduction, and whether or not the reproducer is active during reproduction. We prove that all assisted and unassisted R-models have a related R-model which has the opposite classification. We discuss the relevance to the field of artificial life, give a potential application to the fields of computer virology, and demonstrate reproduction modelling and classification in action using examples.
