Chitosan Nanoparticle-Based System: A New Insight into the Promising Controlled Release System for Lung Cancer Treatment

Lung cancer has been recognized as one of the most often diagnosed and perhaps most lethal cancer diseases worldwide. Conventional chemotherapy for lung cancer-related diseases has bumped into various limitations and challenges, including non-targeted drug delivery, short drug retention period, low therapeutic efficacy, and multidrug resistance (MDR). Chitosan (CS), a natural polymer derived from deacetylation of chitin, and comprised of arbitrarily distributed β-(1-4)-linked d-glucosamine (deacetylated unit) and N-acetyl-d-glucosamine (acetylated unit) that exhibits magnificent characteristics, including being mucoadhesive, biodegradable, and biocompatible, has emerged as an essential element for the development of a nano-particulate delivery vehicle. Additionally, the flexibility of CS structure due to the free protonable amino groups in the CS backbone has made it easy for the modification and functionalization of CS to be developed into a nanoparticle system with high adaptability in lung cancer treatment. In this review, the current state of chitosan nanoparticle (CNP) systems, including the advantages, challenges, and opportunities, will be discussed, followed by drug release mechanisms and mathematical kinetic models. Subsequently, various modification routes of CNP for improved and enhanced therapeutic efficacy, as well as other restrictions of conventional drug administration for lung cancer treatment, are covered.

Zeolitic Imidazolate Framework Nanoencapsulation of CpG for Stabilization and Enhancement of Immunoadjuvancy

Metal-organic frameworks (MOFs) have been used to improve vaccine formulations by stabilizing proteins and protecting them against thermal degradation. This has led to increased 2 immunogenicity of these proteinaceous therapeutics. In this work we show that MOFs can also be used to protect the ssDNA oligomer, CpG, to increase its immunoadjuvancy. By encapsulating phosphodiester CpG in the zinc-based MOF, ZIF-8, the DNA oligomer is protected from nuclease degradation and exhibits improved cellular uptake. As a result, we have been able to achieve drastically enhanced B-cell activation in splenocyte cultures comparable to the current state-of-the-art, phosphorothioate CpG. Furthermore, we have made a direct comparison of micro- and nano-sized MOF for the optimization of particulate delivery of immunoadjuvants to maximize immune activation.

Nanoparticulate drug delivery systems: A revolution in design and development of drugs

The recent developments in nanoparticle-based drug formulations have been helping to address issues around treating challenging diseases. Nanoparticles come in different sizes but usually vary between 100nm to 500nm. For the past few years there has been research going on in the area of drug delivery using particulate delivery systems. Various drug molecules have been modified for both pharmacokinetic and pharmacodynamic properties using nanoparticles as physical approach. Various polymers have been used in the formulation of nanoparticles for drug delivery research to increase therapeutic benefit, while minimizing side effects. Here, we review various aspects of nanoparticle formulation, characterization, effect of their characteristics and their applications in delivery of drug molecules and therapeutic genes. Keywords: nanoparticles, applications in delivery, Liposomes, Dendrimers

Physicochemical characterization of Novel Particulate Delivery Systems for Antitumor/metastatic Therapeutics

The main objective of this project was to overcome the drawbacks of the emulsification techniques during rising a delivery system for a novel and potent anticancer drug, CK-10, projected for enlightening the therapeutic index of the drug. Emulsion/Solvent evaporation and innovative microfluidic techniques were used to frame the nanoparticles. Loading efficiency and in-vitro release were characterized by a modified Lowry assay. Size and zeta potential were analyzed by dynamic light scattering, laser obscuration time, and tuneable pore resistive sensing. Compatibility and shelf life were tested by differential scanning calorimeter and Fourier transform infra-red. The extent of the nanoparticles degradation was measured by color indicator and potentiometric titrations. The result showed that PLGA/B Cyclodextrin nanoparticles had a higher peptide loading efficiency by 53.92% for the novel microfluidic technique as well as higher in-vitro release and better degradation. PLGA/B Cyclodextrin and PLGA/HPMA nanoparticles had a closely related size and zeta potential. It was concluded that the novel microfluidic technique could augment the physicochemical properties of the CK-10 nanoparticles to improve its pharmacokinetics and pharmacodynamics.

Current Status and Perspectives of Oral Therapeutic Protein and Peptide Formulations: A Review

Medicinal formulations have evolved from the use of small molecules that act by blocking various receptors. On the contrary, therapeutic proteins are a class of medicines that have gained increased popularity owing to its low toxicity, high stability and exquisite specificity. Oral delivery of protein drugs is a very interesting but a highly challenging area of medicine that requires advancements in terms of bioavailability of oral drugs. The main objective of the present review is to provide a systematic overview of the various physiological barriers of delivery of therapeutic proteins and novel approaches available in this field in order to counter these physiological barriers. Advances in terms of inhibitors of proteases, permeation enhancers, mucoadhesives, short peptide conjugates, particulate delivery system including nanoparticles. Oral therapeutic proteins face challenges with regard to oral bioavailability, stability of the protein and reproducibility. Among the various strategies, a co-administration of permeation enhancers with protease inhibitors have proven most effective, while particulate delivery system is still under clinical studies in order to be establishes as a method. Overall, a thorough and focused research with sufficient knowledge on the structure-function relationship, substrate specificity and physiological parameters can deliver a potent therapeutic protein with high efficiency.

Phagocytic Uptake of Particles by Immune cells Under Flow Conditions

Particles injected intravenously are thought to be cleared by macrophages residing in the liver and spleen, but they also encounter circulating immune cells. It remains to be determined if the circulating cells can take up particles while flowing in the blood. Here, we use an in vitro peristaltic pump setup that mimics pulsatile blood flow to establish if immune cells take up particles under constant fluidic flow. Our results show that the immune cells do phagocytose under flow conditions, and the uptake depends on the cell type, particle size, and flow rate. We demonstrate that cell lines representing myeloid cells, and primary neutrophils and monocytes are similar or better at taking up sub-micrometer-sized particles under flow compared to static conditions. Experiments with whole blood show that even under the crowding effects of red blood cells, neutrophils and monocytes take up particles while flowing. These data suggest that therapeutics may be delivered to circulating immune cells using particulate delivery systems.

Sonophoretic acceleration of degradation process for vaterite particles delivered into the hair follicles

Intrafollicular drug delivery is beneficial in terms of both localized therapy of relevant skin disorders and systemic transportation of bioactive molecules. Vaterite particles are capable of loading and delivering various substances to hair follicles. Possibility to control the duration of their intrafollicular degradation can improve such a particulate delivery system. Here, we propose the use of sonophoresis (1 MHz, 1 W/cm2 ) to accelerate the resorption of vaterite carriers inside the hair follicles of rats in vivo. The effect of sonication is demonstrated utilizing optical coherence tomography monitoring of the skin and scanning electron microscopy investigation of the plucked hairs. A nine-minute post-treatment of skin in the site of particle delivery allowed us to almost halve the time of their degradation.

Role of metformin in various pathologies: state-of-the-art microcapsules for improving its pharmacokinetics

Metformin was originally derived from a botanical ancestry and became the most prescribed, first-line therapy for Type 2 diabetes in most countries. In the last century, metformin was discovered twice for its antiglycemic properties in addition to its antimalarial and anti-influenza effects. Metformin exhibits flip-flop pharmacokinetics with limited oral bioavailability. This review outlines metformin pharmacokinetics, pharmacodynamics and recent advances in polymeric particulate delivery systems as a potential tool to target metformin delivery to specific tissues/organs. This interesting biguanide is being rediscovered this century for multiple clinical indications as anticancer, anti-aging, anti-inflammatory, anti-Alzheimer’s and much more. Microparticulate delivery systems of metformin may improve its oral bioavailability and optimize the therapeutic goals expected.