Comparative whole corona fingerprinting and protein adsorption thermodynamics of PLGA and PCL nanoparticles in human serum.

Nanoparticles (NPs) based on biocompatible and biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) represent effective systems for systemic drug delivery. Upon injection into the blood circuit, the NP surface is rapidly modified due to adsorption of proteins that form a 'protein corona' (PC). The PC plays an important role in cellular targeting, uptake and NP bio-distribution. Hence, the study of interactions between NPs and serum proteins appears as key for biomedical applications and safety of NPs. In the present work, we report on the comparative protein fluorescence quenching extent, thermodynamics of protein binding and identification of proteins in the soft and hard corona layers of PLGA and PCL NPs. NPs were prepared via a single emulsion-solvent evaporation technique and characterized with respect to size, zeta potential, surface morphology and hydrophobicity. Protein fluorescence quenching experiments were performed against human serum albumin. The thermodynamics of serum protein binding onto the NPs was studied using isothermal titration calorimetry. Semi-quantitative analysis of proteins in the PC layers was conducted using gel electrophoresis and mass spectrometry using human serum. Our results demonstrated the influence of particle hydrophobicity on the thermodynamics of protein binding. Human serum proteins bind to a greater extent and with greater affinity to PCL NPs than PLGA NPs. Several proteins were detected in the hard and soft corona of the NPs, representing their unique proteome fingerprints. Some proteins were unique to the PCL NPs. We anticipate that our findings will assist with rational design of polymeric NPs for effective drug delivery applications.

The Macrophage Response to Mycobacterium tuberculosis and Opportunities for Autophagy Inducing Nanomedicines for Tuberculosis Therapy.

The major causative agent of tuberculosis (TB), i.e., Mycobacterium tuberculosis (Mtb), has developed mechanisms to evade host defense responses and persist within host cells for prolonged periods of time. Mtb is also increasingly resistant to existing anti-TB drugs. There is therefore an urgent need to develop new therapeutics for TB and host directed therapies (HDTs) hold potential as effective therapeutics for TB. There is growing interest in the induction of autophagy in Mtb host cells using autophagy inducing compounds (AICs). Nanoparticles (NPs) can enhance the effect of AICs, thus improving stability, enabling cell targeting and providing opportunities for multimodal therapy. In this review, we focus on the macrophage responses to Mtb infection, in particular, the mechanistic aspects of autophagy and the evasion of autophagy by intracellular Mtb. Due to the overlap between the onset of autophagy and apoptosis; we also focus on the relationship between apoptosis and autophagy. We will also review known AICs in the context of Mtb infection. Finally, we discuss the applications of NPs in inducing autophagy with the intention of sharing insights to encourage further research and development of nanomedicine HDTs for TB therapy.

Polymeric Micellar Formulation Enhances Antimicrobial and Anticancer Properties of Salinomycin.

PURPOSE: Salinomycin (SAL) is a polyether compound that exhibits strong antimicrobial as well as anticancer activity. Nanomedicine has been at the forefront of drug delivery research with the aim of increasing the efficacy, specificity and reduce toxicity of drugs. There is an intersection between infection and cancer, and cancer patients are prone to bacterial infections. In this study, polymeric micelles were prepared using Pluronic® F127 (PM) to encapsulate SAL (PM_SAL) with the view of enhancing antimicrobial and anticancer activity. METHODS: A Quality by Design (QbD) approach was utilized to synthesize PM_SAL, and nanoformulation activity was determined against bacterial (S. aureus, MRSA and E. coli). Effects on cancer cell line A549, i.e. cell viability, prevention of P-gp efflux, vimentin expression, effects on migratory ability of A549 cells. Anticancer activity was determined by ability to eradicate cancer stem-like cells. RESULTS: PM_SAL demonstrated only efficacy against MRSA, being even higher than that obtained with SAL. In A549 cells, a 15-fold increase in P-gp's expression as well as a significant decrease of the cell's migration, was observed. CONCLUSIONS: PM_SAL can interfere with the oncogenic protein VIM, involved in the crucial mechanisms EMT, downregulating its expression. Altogether data obtained indicates that this antibiotic and the developed polymeric micelle system is a very promising inhibitor of tumor cell growth.