Development of a liquid chromatography-tandem mass spectrometry method for the analysis of docetaxel-loaded Poly(lactic-co-glycolic acid) nanoparticles.

Docetaxel is among the most effective chemotherapeutic agents used for the treatment of solid tumors, such as breast cancer. Targeting docetaxel to the tumor site would increase the safety and efficacy of the treatment. The focus of this work was to develop an efficient liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify docetaxel entrapped in optimized poly lactic-co-glycolic acid (PLGA) nanoparticles.

A Single-Dose Intramuscular Nanoparticle Vaccine With or Without Prior Intrauterine Priming Triggers Specific Uterine and Colostral Mucosal Antibodies and Systemic Immunity in Gilts but Not Passive Protection for Suckling Piglets.

An effective single-dose vaccine that protects the dam and her suckling offspring against infectious disease would be widely beneficial to livestock animals. We assessed whether a single-dose intramuscular (i.m.

Interplay between cellular metabolism and DNA viruses.

Viruses as intracellular pathogens take over the host metabolism and reprogram to facilitate optimal virus production. DNA viruses can cause alterations in several metabolic pathways, including aerobic glycolysis also known as the Warburg effect, pentose phosphate pathway activation, and amino acid catabolism such as glutaminolysis, nucleotide biosynthesis, lipid metabolism, and amino acid biosynthesis. The available energy for productive infection can be increased in infected cells via modification of different carbon source utilization.

Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action.

The ultimate goal for vaccination is the generation of a safe and effective immune response that protects against diseases [...

Establishment of the tandem mass spectrometric fingerprints of taxane-based anticancer compounds.

Rationale: Compounds in the taxane drug family are among the most successful and effective chemotherapeutic agents used in the treatment of solid tumors, such as breast, ovarian, and prostate cancers. The tandem mass spectrometric (MS/MS) fragmentation behavior of these compounds is described in detail, and a generalized MS/MS fingerprint is established for the first time.

Methods: Five compounds, namely paclitaxel, docetaxel, cabazitaxel, cephalomannine, and baccatin III, were evaluated.

Combination of Innate Immune Modulators as Vaccine Adjuvants in Mice.

The development of new, effective, and safe vaccines necessarily requires the identification of new adjuvant(s) to enhance the potency and longevity of antigen-specific immune responses. In the present study, we compare the antibody-mediated and cell-mediated immune (CMI) responses within groups of mice vaccinated subcutaneously with ovalbumin (OVA; as an experimental antigen) plus polyphosphazene (an innate immune modulator), Polyinosinic:polycytidylic acid (poly-I:C; (an RNA mimetic) and glycopeptide ARC5 (which is a Toll-like receptor (TLR), TLR2 ligand and PAM3CSK4 analogue) formulated together in a soluble vaccine. We also investigated the effect of a polymeric nanoparticle of ARC4 and ARC7 (which are a novel muramyl dipeptide analogue and a monophosophoryl lipid A (MPLA) analogue, respectively) plus OVA +/- ARC5 as a subcutaneous vaccine in mice.

Prospects for RNAi Therapy of COVID-19.

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics.

A robust systematic design: Optimization and preparation of polymeric nanoparticles of PLGA for docetaxel intravenous delivery.

Poly (lactide-co-glycolide) (PLGA) is a biocompatible, biodegradable, and non-toxic polymer used in a variety of biomedical and pharmaceutical applications. Polymeric nanoparticles prepared from PLGA have been extensively used as delivery vehicles of various chemotherapeutic agents. The variability of PLGA polymer and nanoparticle fabrication process potentially results in variability of particle characteristics.

Potentiating Antigen Specific Immune Response by Targeted Delivery of the PLGA-Based Model Cancer Vaccine.

Targeted delivery of vaccine has the potential to localize the therapeutic agent to a target tissue with minimum side-effects. This article presents the development of a model targeted immunotherapeutic approach that will harness effective T cell response. Here, we investigated the impact of a model nanoparticulate cancer vaccine on the immune system of in vivo mice models.

Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer.

In nanomedicine, targeted therapeutic nanoparticle (NP) is a virtual outcome of nanotechnology taking the advantage of cancer propagation pattern. Tying up all elements such as therapeutic or imaging agent, targeting ligand, and cross-linking agent with the NPs is the key concept to deliver the payload selectively where it intends to reach. The microenvironment of tumor tissues in lymphatic vessels can also help targeted NPs to achieve their anticipated accumulation depending on the formulation objectives.

Design and immunological evaluation of anti-CD205-tailored PLGA-based nanoparticulate cancer vaccine.

The aim of this research was to develop a targeted antigen-adjuvant assembled delivery system that will enable dendritic cells (DCs) to efficiently mature to recognize antigens released from tumor cells. It is important to target the DCs with greater efficiency to prime T cell immune responses. In brief, model antigen, ovalbumin (OV), and monophosphoryl lipid A adjuvant were encapsulated within the nanoparticle (NP) by double emulsification solvent evaporation method.

Pharmacokinetic Consequences of PLGA Nanoparticles in Docetaxel Drug Delivery.

Background: Cancer chemotherapy is accompanied with administration of highly potent cytotoxic agents in doses that can result in non-specific drug toxicity and side effects. Chemotherapeutic agents possess limitations such as lack of water solubility, high volume of distribution, poor bioavailability, narrow therapeutic indices, multi-drug resistance, etc. that raise serious matters of concern regarding drug's pharmaceutical and clinical aspects.

Advances in the treatment of relapsing-remitting multiple sclerosis: the role of pegylated interferon β-1a.

Multiple sclerosis (MS) is a progressive, neurodegenerative disease with unpredictable phases of relapse and remission. The cause of MS is unknown, but the pathology is characterized by infiltration of auto-reactive immune cells into the central nervous system (CNS) resulting in widespread neuroinflammation and neurodegeneration. Immunomodulatory-based therapies emerged in the 1990s and have been a cornerstone of disease management ever since.

Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile.

Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug's pharmacokinetics related to the conventional formulation. Poly(lactide--glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration.

Investigation and optimization of formulation parameters on preparation of targeted anti-CD205 tailored PLGA nanoparticles.

The purpose of this study was to assess the effect of various formulation parameters on anti-CD205 antibody decorated poly(d, l-lactide co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to target dendritic cells (DCs). In brief, emulsification solvent evaporation technique was adapted to design NP formulations using two different viscosity grades (low and high) of both ester and carboxylic acid terminated PLGA. Incorporation of ligand was achieved following physical adsorption or chemical conjugation processes.

Optimization of nanoparticles for cardiovascular tissue engineering.

Nano-particulate delivery systems have increasingly been playing important roles in cardiovascular tissue engineering. Properties of nanoparticles (e.g.

Nano-pharmaceutical formulations for targeted drug delivery against HER2 in breast cancer.

Nanotechnology has revolutionized fundamental opportunities for higher specific drug delivery with minimum side effects. Since its inception, the goal of nanotechnology has been to advance effective and reliable systems for precise anti-cancer therapy and diagnosis. To accomplish this goal, bio-conjugation strategies of therapeutic agents loaded nanoparticles with monoclonal antibodies or their analogues have demonstrated a targeted approach both in vitro and in vivo.

Rate-programming of nano-particulate delivery systems for smart bioactive scaffolds in tissue engineering.

Development of smart bioactive scaffolds is of importance in tissue engineering, where cell proliferation, differentiation and migration within scaffolds can be regulated by the interactions between cells and scaffold through the use of growth factors (GFs) and extra cellular matrix peptides. One challenge in this area is to spatiotemporally control the dose, sequence and profile of release of GFs so as to regulate cellular fates during tissue regeneration. This challenge would be addressed by rate-programming of nano-particulate delivery systems, where the release of GFs via polymeric nanoparticles is controlled by means of the methods of, such as externally-controlled and physicochemically/architecturally-modulated so as to mimic the profile of physiological GFs.

Immunoadjuvant activity of the nanoparticles' surface modified with mannan.

Mannan (MN) is the natural ligand for mannose receptors, which are widely expressed on dendritic cells (DCs). The purpose of this study was to assess the effect of formulation parameters on the immunogenicity of MN-decorated poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to stimulate DC phenotypic as well as functional maturation. For this purpose, NPs were formulated from either ester-terminated or COOH-terminated PLGA.

Presence of monoterpene synthase in four Labiatae species and Solid-Phase Microextraction- Gas chromatography-Mass Spectroscopy analysis of their aroma profiles.

Background: The family Lamiaceae (Labiatae) has included some medicinal plants. some monoterpene synthases, including linalool and limonene synthases, have been cloned and functionally characterized from several plants of Labiatae family.

Materials And Methods: In this study, presence of linalool and limonene synthases, in four species of Labiatae family including Nepeta cataria, Lavandula angustifolia, Hyssopus officinalis and Salvia sclarea has been determined by molecular biological techniques together with the Head space SPME - GC-MS analysis of the aroma profile of these species.

Biogenic trypanocidal sesquiterpenes: lead compounds to design future trypanocidal drugs - a mini review.

Human trypanosomiasis is a parasitic disease among poor people in Africa and Latin America. Therapy against African and American trypanosomiasis is based on a few drugs that often cause severe side-effects. Therefore, it is essential to develop drug discovery especially from natural origins.

Antitumor efficacy of photodynamic therapy using novel nanoformulations of hypocrellin photosensitizer SL052.

Recent preclinical and clinical testing of hypocrellin-based photosensitizer SL052 for use in photodynamic therapy (PDT) of cancer has shown encouraging results. Further optimization of its formulation for delivery could considerably extend the therapeutic efficiency of this drug. A nanoformulation encapsulating SL052 into biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) was developed using a single-emulsion solvent evaporation technique and characterized in terms of particle size and loading of the photosensitizing agent.

Targeting dendritic cells with nano-particulate PLGA cancer vaccine formulations.

Development of safe and effective cancer vaccine formulation is a primary focus in the field of cancer immunotherapy. The recognition of the crucial role of dendritic cells (DCs) in initiating anti-tumor immunity has led to the development of several strategies that target vaccine antigens to DCs as an attempt for developing potent, specific and lasting anti-tumor T cell responses. The main objective of this review is to provide an overview on the application of poly (d,l-lactic-co-glycolic acid) nanoparticles (PLGA-NPs) as cancer vaccine delivery system and highlight their potential in the development of future therapeutic cancer vaccines.

STAT3 Knockdown in B16 Melanoma by siRNA Lipopolyplexes Induces Bystander Immune Response In Vitro and In Vivo.

Persistent activation of STAT3 plays a major role in cancer progression and immune escape. Therefore, targeting STAT3 in tumors is essential to enhance/reactivate antitumor immune response. In our previous studies, we demonstrated the efficacy of stearic acid-modified polyethylenimine (PEI-StA) in promoting small interfering RNA (siRNA) silencing of STAT3 in B16.

Activation of antigen-specific T cell-responses by mannan-decorated PLGA nanoparticles.

Purpose: Mannosylation of vaccines is a promising strategy to selectively target vaccine antigens to the mannose receptor expressed on dendritic cells (DCs). The purpose of this study was to investigate the effect of mannan (MN) chemically conjugated to poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) on antigen-specific T-cell responses elicited by a model antigen (ovalbumin, OVA) loaded in PLGA-NPs.

Methods: In vitro T-cell proliferation assay was done to assess the ability of DCs treated with OVA-NPs (±MN decoration) to induce antigen-specific T-cell activation.