Patrícia Figueiredo

Angiopep2-functionalized polymersomes for targeted doxorubicin delivery to glioblastoma cells

A targeted drug delivery nanosystem for glioblastoma multiforme (GBM) based on polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS-PMOXA) diblock copolymers was developed to evaluate their potential to actively target brain cancer cells and deliver anticancer drugs. Angiopep2 was conjugated to the surface of preformed Ps to target the low density lipoprotein receptor-related protein 1 that are overexpressed in blood brain barrier (BBB) and glioma cells. The conjugation efficiency yield for angiopep2 was estimated to be 24%. The angiopep2-functionalized Ps showed no cellular toxicity after 24h and enhanced the cellular uptake around 5 times more in U87MG glioblastoma cells compared to the non-targeted Ps. The encapsulation efficiency of doxorubicin (DOX) in Ps was 13% by co-solvent method, compared to a film rehydration method (4%). The release profiles of the DOX from Ps showed a release of 42% at pH 5.5 and 40% at pH 7.4 after 24h, indicating that Ps can efficiently retain the DOX with a slow release rate. Furthermore, the in vitro antiproliferative activity of DOX-loaded Ps-Angiopep2 showed enhanced toxicity to U87MG glioblastoma cells, compared to non-targeted Ps. Overall, our in vitro results suggested that angiopep2-conjugated Ps can be used as nanocarriers for efficient targeted DOX delivery to glioblastoma cells.

Preparation and biological evaluation of ethionamide-mesoporous silicon nanoparticles against Mycobacterium tuberculosis

Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB).

Production of pure drug nanocrystals and nano co-crystals by confinement methods

ABSTRACT The use of drug nanocrystals in the drug formulation is increasing due to the large number of poorly water‐soluble drug compounds synthetized and due to the advantages brought by the nanonization process. The downsizing processes are done using a top‐down approach (milling and homogenization currently employed at the industrial level), while the crystallization process is performed by bottom‐up techniques (e.g., antisolvent precipitation, use of supercritical fluids or spray and freeze drying). In addition, the production of nanocrystals in confined environment can be achieved within microfluidics channels. This review analyzes the processes for the preparation of nanocrystals and co‐crystals, divided by top‐down and bottom‐up approaches, together with their combinations. The combination of both strategies merges the favorable features of each process and avoids the disadvantages of single processes. Overall, the applicability of drug nanocrystals is highlighted by the widespread research on the production processes at the engineering, pharmaceutical, and nanotechnology level. Graphical abstract Figure. No caption available.

Mesoporous Silica Nanoparticles for Targeted and Stimuli‐Responsive Delivery of Chemotherapeutics: A Review

Mesoporous silica nanoparticles (MSNs) exhibit the typical characteristics of inorganic materials that make them promising drug delivery carriers for cancer therapy. Their structural properties allow the targeted delivery of chemotherapeutic drugs to enhance drug efficacy and reduce adverse effects. The functionalization of MSNs with targeting ligands to a specific tissue/cell and stimuli‐responsive capping materials to seal drugs inside the MSNs pores are widely studied for biomedical and pharmaceutical applications. Furthermore, multiple stimuli‐responsive MSN‐based drug delivery systems are developed to enhance the delivery of anticancer drugs to their specific target and thereby improve the release of the drugs at the intended site. In addition, several toxicity studies are conducted to evaluate the biosafety and biocompatibility of MSNs. Although MSNs present reduced toxicity compared to colloidal silica, they can induce cytotoxicity associated with oxidative stress by increased reactive oxygen species production and decreased glutathione levels that can ultimately lead to cell death. However, different modifications to control morphology and surface composition can be applied to overcome the biocompatibility concerns. In this review, a comprehensive overview of the controlled synthesis, functionalization, targeting and biocompatibility of MSNs, as well as their biomedical application as a chemotherapeutic delivery system is provided.