Development of Novel EE/Alginate Polyelectrolyte Complex Nanoparticles for Lysozyme Delivery: Physicochemical Properties and In Vitro Safety.

The number of biologic drugs has increased in the pharmaceutical industry due to their high therapeutic efficacy and selectivity. As such, safe and biocompatible delivery systems to improve their stability and efficacy are needed. Here, we developed novel cationic polymethacrylate-alginate (EE-alginate) pNPs for the biologic drug model lysozyme (Lys). The impact of variables such as total charge and charge ratios over nanoparticle physicochemical properties as well as their influence over in vitro safety (viability/proliferation and cell morphology) on HeLa cells was investigated. Our results showed that electrostatic interactions between the EE-alginate and lysozyme led to the formation of EE/alginate Lys pNPs with reproducible size, high stability due to their controllable zeta potential, a high association efficiency, and an in vitro sustained Lys release. Selected formulations remained stable for up to one month and Fourier transform-Infrared (FT-IR) showed that the functional groups of different polymers remain identifiable in combined systems, suggesting that Lys secondary structure is retained after pNP synthesis. EE-alginate Lys pNPs at low concentrations are biocompatible, while at high concentrations, they show cytotoxic for HeLa cells, and this effect was found to be dose-dependent. This study highlights the potential of the EE-alginate, a novel polyelectrolyte complex nanoparticle, as an effective and viable nanocarrier for future drug delivery applications.

Preparation of a novel lipid-core micelle using a low-energy emulsification method.

High-energy methods for the manufacturing of nanomedicines are widely used; however, interest in low-energy methods is increasing due to their simplicity, better control over the process, and energy-saving characteristics during upscaling. Here, we developed a novel lipid-core micelle (LCM) as a nanocarrier to encapsulate a poorly water-soluble drug, nifedipine (NFD), by hot-melt emulsification, a low-energy method. LCMs are self-assembling colloidal particles composed of a hydrophobic core and a hydrophilic shell. Hybrid materials, such as Gelucire 44/14, are thus excellent candidates for their preparation. We characterized the obtained nanocarriers for their colloidal properties, drug loading and encapsulation efficiency, liquid state, stability, and drug release. The low-energy method hot-melt emulsification was successfully adapted for the manufacturing of small and narrowly dispersed LCMs. The obtained LCMs had a small average size of ~ 11 nm and a narrow polydispersity index (PDI) of 0.228. These nanocarriers were able to increase the amount of NFD dispersible in water more than 700-fold. Due to their sustained drug release profile and the PEGylation of Gelucire 44/14, these nanocarriers represent an excellent starting point for the development of drug delivery systems designed for long circulation times and passive targeting.

Nanomedicine and nanotoxicology: the pros and cons for neurodegeneration and brain cancer.

Current strategies for brain diseases are mostly symptomatic and noncurative. Nanotechnology has the potential to facilitate the transport of drugs across the blood-brain barrier and to enhance their pharmacokinetic profile. However, to reach clinical application, an understanding of nanoneurotoxicity in terms of oxidative stress and inflammation is required. Emerging evidence has also shown that nanoparticles have the ability to alter autophagy, which can induce inflammation and oxidative stress, or vice versa. These effects may increase neurodegenerative processes damage, but on the other hand, they may have benefits for brain cancer therapies. In this review, we emphasize how nanomaterials may induce neurotoxic effects focusing on neurodegeneration, and how these effects could be exploited toward brain cancer treatment.