Polymeric Nanoparticles for Biomedical Applications.

Polymeric nanoparticles (NPs), utilized extensively in biomedical applications, have received increasing interest in the preceding years and today represent an established part of the nanotechnology field [...].

Fighting Methicillin-Resistant Staphylococcus aureus with Targeted Nanoparticles.

Antimicrobial resistance (AMR) is considered one of the greatest threats to global health. Methicillin-resistant Staphylococcus aureus (MRSA) remains at the core of this threat, accounting for about 90% of S. aureus infections widespread in the community and hospital settings. In recent years, the use of nanoparticles (NPs) has emerged as a promising strategy to treat MRSA infections. NPs can act directly as antibacterial agents via antibiotic-independent activity and/or serve as drug delivery systems (DDSs), releasing loaded antibiotics. Nonetheless, directing NPs to the infection site is fundamental for effective MRSA treatment so that highly concentrated therapeutic agents are delivered to the infection site while directly reducing the toxicity to healthy human cells. This leads to decreased AMR emergence and less disturbance of the individual's healthy microbiota. Hence, this review compiles and discusses the scientific evidence related to targeted NPs developed for MRSA treatment.

Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials.

Neurodegenerative diseases are caused by the gradual loss of neurons' function. These neurological illnesses remain incurable, and current medicines only alleviate the symptoms. Given the social and economic burden caused by the rising frequency of neurodegenerative diseases, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compounds' therapeutic effects for neurodegenerative disease treatment have been investigated in numerous in vitro and in vivo studies, only few have moved to clinical trials. This article provides the first systematic review of the clinical trials evaluating natural compounds' safety and efficacy for the treatment of the five most prevalent neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease.

Transferrin-functionalized liposomes loaded with vitamin VB12 for Alzheimer's disease therapy.

Despite the efforts of the pharmaceutical and research sectors, Alzheimer's disease (AD) remains incurable, imposing the demand for new effective strategies. Vitamin B12 (VB12) has aroused interest due to its in vitro anti-amyloidogenic properties. However, the high molecular weight and hydrophilicity of VB12 are the main obstacles to its clinical application by hindering its passage through the blood-brain barrier (BBB). In recent years, drug delivery systems (DDSs) capable of transporting molecules across the BBB have gained attention for their effective brain delivery. In this work, VB12-loaded liposomes functionalized with transferrin (Tf) were produced, envisaging the dual-targeting of VB12 to the BBB and neuronal cells, due to the overexpression of Tf receptors in these cells. The produced liposomes presented sizes smaller than 200 nm, with low polydispersity and neutral zeta potential, being suitable for brain delivery. The nanoparticles exhibited an adequate encapsulation efficiency, a sustained release of VB12 for 9 days, and physical stability at storage conditions for up to 2 months. The developed nanosystem was capable of delaying the formation of Aß fibrils and disrupting mature fibrils, highlighting its great potential for the prevention and treatment of AD.

Interaction of natural compounds with biomembrane models: A biophysical approach for the Alzheimer's disease therapy.

Natural compounds such as caffeine (CA), gallic acid (GA) and tannic acid (TA) have been reported to be useful for Alzheimer's disease (AD) therapy. It was proved that some natural compounds inhibit the formation of senil plaques composed by beta-amyloid peptide (Aß), a hallmark of AD. Evidences suggest that the therapeutic activity of compounds depends of their interaction with biological membranes. To understand why these compounds fail in vivo and in clinical trials, it is important to evaluate their pharmacokinetics properties. Thus, a biophysical approach to study drug-membrane interactions is essential to understand the mechanisms by which the drugs interact with the cellular membranes and affect the Aß production, aggregation and clearance pathways. 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol (chol) were used to mimic the biophysical properties of cell membranes and study their interactions with these compounds. The partition coefficient, influence on membrane fluidity and location within the bilayer of the drugs were studied by derivative spectrophotometry, dynamic light scattering and fluorescence quenching, respectively. The results suggest that TA exhibited a significant higher partition than CA and GA and a preferential location near to the polar head of bilayer. The obtained results may explain the therapeutic mechanisms reported for these natural compounds.

PLGA nanoparticles as a platform for vitamin D-based cancer therapy.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were studied as drug delivery vehicles for calcitriol, the active form of vitamin D3. In vitro effects of calcitriol encapsulated in PLGA nanoparticles were evaluated with respect to free calcitriol on human pancreatic cell lines, S2-013 and hTERT-HPNE, and the lung cancer cell line A549. Encapsulated calcitriol retained its biological activity, reducing the cell growth. Cytotoxicity assays demonstrated that encapsulation of calcitriol enhanced its inhibitory effect on cell growth at a concentration of 2.4 µM for the S2-013 cells (91%) and for A549 cells (70%) comparared to the free calcitriol results. At this concentration the inhibitory effect on nontumor cells (hTERT-HPNE) decreased to 65%. This study highlights the ability of PLGA nanoparticles to deliver vitamin D3 into cancer cells, with major effects regarding cancer cell cycle arrest and major changes in the cell morphological features.