Lipid-Based Inhalable Micro- and Nanocarriers of Active Agents for Treating Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) afflicts about 2 million people worldwide, with both genetic (familial) and environmental factors contributing to its development and spread. The inadequacy of currently available therapeutic techniques, such as surgery, chemotherapy, and radiation therapy, in addressing NSCLC is reflected in the very low survival rate of this disease. Therefore, newer approaches and combination therapy regimens are required to reverse this dismal scenario. Direct administration of inhalable nanotherapeutic agents to the cancer sites can potentially lead to optimal drug use, negligible side effects, and high therapeutic gain. Lipid-based nanoparticles are ideal agents for inhalable delivery owing to their high drug loading, ideal physical traits, sustained drug release, and biocompatibility. Drugs loaded within several lipid-based nanoformulations, such as liposomes, solid-lipid nanoparticles, lipid-based micelles, etc., have been developed as both aqueous dispersed formulations as well as dry-powder formulations for inhalable delivery in NSCLC models in vitro and in vivo. This review chronicles such developments and charts the future prospects of such nanoformulations in the treatment of NSCLC.

Emerging Prospects of Nanozymes for Antibacterial and Anticancer Applications.

The ability of some nanoparticles to mimic the activity of certain enzymes paves the way for several attractive biomedical applications which bolster the already impressive arsenal of nanomaterials to combat deadly diseases. A key feature of such 'nanozymes' is the duplication of activities of enzymes or classes of enzymes, such as catalase, superoxide dismutase, oxidase, and peroxidase which are known to modulate the oxidative balance of treated cells for facilitating a particular biological process such as cellular apoptosis. Several nanoparticles that include those of metals, metal oxides/sulfides, metal-organic frameworks, carbon-based materials, etc., have shown the ability to behave as one or more of such enzymes. As compared to natural enzymes, these artificial nanozymes are safer, less expensive, and more stable. Moreover, their catalytic activity can be tuned by changing their size, shape, surface properties, etc. In addition, they can also be engineered to demonstrate additional features, such as photoactivated hyperthermia, or be loaded with active agents for multimodal action. Several researchers have explored the nanozyme-mediated oxidative modulation for therapeutic purposes, often in combination with other diagnostic and/or therapeutic modalities, using a single probe. It has been observed that such synergistic action can effectively by-pass the various defense mechanisms adapted by rogue cells such as hypoxia, evasion of immuno-recognition, drug-rejection, etc. The emerging prospects of using several such nanoparticle platforms for the treatment of bacterial infections/diseases and cancer, along with various related challenges and opportunities, are discussed in this review.

Mechanistic interaction studies of synthesized ZIF-8 nanoparticles with bovine serum albumin using spectroscopic and molecular docking approaches.

Numerous studies have shown that nanosized zeolitic imidazolate framework particles (ZIF-8 NPs) serve as promising vehicles for pH-responsive drug delivery. An understanding of their interaction with serum proteins present in physiological systems will thus be of critical importance. In this work, monodisperse ZIF-8 NPs with an average size of 60 nm were synthesized at room temperature and characterized for their various physicochemical properties. Bovine serum albumin (BSA) was used as model serum protein for various interaction studies with ZIF-8 NPs. Spectroscopic techniques such as UV-visible and fluorescence spectroscopy indicated the formation of a ground-state complex with a binding constant of the order 103 M-1 and a single binding site. Steady-state and time-resolved fluorescence spectroscopy confirmed the mechanism of quenching to be static. Conformational changes in the secondary structure of BSA were observed using CD and FT-IR spectroscopies. Binding sites were explored using molecular docking studies.

Biomedical In Vivo Studies with ORMOSIL Nanoparticles Containing Active Agents.

Organically modified silica (ORMOSIL) nanoparticles have found many biomedical applications and emerged as biocompatible and efficient carriers of diagnostic and therapeutic agents, such as fluorophores, drugs, and DNA. Herein, we describe two major in vivo studies exemplifying the use of these nanoparticles as carriers of active agents. The first part of this report details a systemic administration and biodistribution of radiolabeled and fluorophore-incorporated ORMOSIL nanoparticles in mice. The second part of this report focuses on the use of ORMOSIL nanoparticles as carriers of plasmid DNA for nonviral gene delivery to the mouse brain. We provide detailed protocols describing preparation and characterization of ORMOSIL nanoparticles, methods used for loading the particles with active agents (e.g., radioimaging agents, plasmid DNA), and in vivo administration of the particles.

Doxorubicin-loaded casein nanoparticles for drug delivery: Preparation, characterization and in vitro evaluation.

Casein, a milk protein that self-assembles to form micelles in aqueous solution, can bind to a wide range of drugs (hydrophilic and hydrophobic). Herein, a low cost and facile method was reported to prepare casein nanoparticles loaded with an anticancer drug, doxorubicin (DOX). The particles were fabricated by adding an excess of Ca2+ ions which brings the soluble casein present in the solution into the micellar framework to form dense nanoparticles. The binding between the drug and the macromolecule was confirmed using fluorescence studies. Circular Dichroism (CD) shows that upon addition of excess Ca2+ the protein chains rearrange. The nanoparticles were characterized by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and dynamic light scattering (DLS). The release at pH 1 was higher than the physiological pH making this formulation potent for delivering the drug to the stomach via the oral route. The DOX attached with casein showed improved efficacy, i.e., better cytotoxicity against human pancreatic carcinoma cell line, PANC 1 cells as compared to the free drug of the same concentration, owing to higher cell uptake of the macromolecule.