Doxorubicin-Intercalated Li-Al-Based LDHs as Potential Drug Delivery Nanovehicle with pH-Responsive Therapeutic Cargo for Tumor Treatment.

Clinical oncology is currently experiencing a technology bottleneck due to the expeditious evolution of therapy defiance in tumors. Although drugs used in chemotherapy work for a sort of cell death with potential clinical application, the effectiveness of chemotherapy-inducing drugs is subject to several endogenous conditions when used alone, necessitating the urgent need for controlled mechanisms. A tumor-targeted drug delivery therapy using Li-Al (M/M)-based layered double hydroxide (LDHs) family has been proposed with the general chemical formula [M M (OH)][(A).

Dominant B cell-T cell epitopes instigated robust immune response in-silico against Scrub Typhus.

Scrub typhus, a potentially life-threatening infectious disease, is attributed to bacteria Orientia tsutsugamushi (O. tsutsugamushi). The transmission of this illness to humans occurs through the bite of infected chiggers, which are the larval forms of mites belonging to the genus Leptotrombidium.

Super epitope dengue vaccine instigated serotype independent immune protection in-silico.

Dengue becomes the most common life-threatening infectious arbovirus disease globally, with prevalence in the tropical and subtropical areas. The major clinical features include dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), a condition of hypovolemic shock. Four different serotypes of the dengue virus, known as dengue virus serotype (DENV)- 1, 2, 3 and 4 can infect humans.

Ordered Mesoporous Silica Delivering siRNA as Cancer Nanotherapeutics: A Comprehensive Review.

Nanosized mesoporous silica has emerged as a promising flexible platform delivering siRNA for cancer treatment. This ordered mesoporous nanosized silica provides attractive features of well-defined and tunable porosity, structure, high payload, and multiple functionalizations for targeted delivery and increasing biocompatibility over other polymeric nanocarriers. Moreover, it also overcomes the lacunae associated with traditional administration of drugs.

Stimuli-responsive magnetic silica-poly-lactic-co-glycolic acid hybrid nanoparticles for targeted cancer chemo-immunotherapy.

Chemotherapy and immunotherapy are two important modalities in cancer management. However, due to multiple reasons, a monotherapy is only partially effective. Hence, if used concurrently in targeted and stimuli-responsive manner, it could have been superior therapeutically.

Beyond the polysaccharide and glycoconjugate vaccines for Streptococcus pneumoniae: Does protein/peptide nanovaccines hold promises?

Streptococcus pneumoniae having almost 98 serotypes and being common cause of acute otitis media, pneumonia, bacteremia, meningitis etc., which results in high mortality and morbidity globally. Although vaccines like PCV-13 and PPV-23 are available, some problems like serotype replacement and poor immunogenicity in children, old age and immunocompromised people has been observed.

Immunogenicity Evaluation of Thermostable Microparticles Entrapping Receptor Binding Domain of SARS-CoV-2 by Single Point Administration.

Receptor binding domain (RBD) of SARS-CoV-2 is a prime vaccine target against which neutralizing antibody responses are directed. Purified RBD as a vaccine candidate warrants administration of multiple doses along with adjuvants and use of delivery systems to improve its immunogenicity. The present investigation examines the immunogenicity of RBD delivered by biodegradable polymer particles from single dose administration.

RBD decorated PLA nanoparticle admixture with aluminum hydroxide elicit robust and long lasting immune response against SARS-CoV-2.

Nanoparticles-based multivalent antigen display has the capability of mimicking natural virus infection characteristics, making it useful for eliciting potent long-lasting immune response. Several vaccines are developed against global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However these subunit vaccines use mammalian expression system, hence mass production with rapid pace is a bigger challenge.

Microparticles entrapping pneumococcal protein SP0845 show improved immunogenicity and temperature stability.

Protein based vaccines are the most safe and affordable strategy to combat pneumococcal disease circumventing the limitations of conventional polysaccharide-based vaccines like serotype dependence, high cost and inability to be administered to immunocompromised. SP0845 is a highly conserved vaccine candidate shown to provide protection against heterologous strains of Streptococcus pneumoniae, the primal cause of pneumonia. However, the associated poor immunogenicity warrants the need for adjuvants and multiple doses to mount desired responses.

Cellular uptake of polylactide particles induces size dependent cytoskeletal remodeling in antigen presenting cells.

Phagocytosis of particulate vaccine delivery systems is a critical immune mechanism involved in antigen capture and processing by macrophages and dendritic cells. The internalization and degradation of the particles involve a complex sequence of events. This process coordinates lipids, signaling proteins, and the cytoskeleton.

Impact of Microbiota: A Paradigm for Evolving Herd Immunity against Viral Diseases.

Herd immunity is the most critical and essential prophylactic intervention that delivers protection against infectious diseases at both the individual and community level. This process of natural vaccination is immensely pertinent to the current context of a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection around the globe. The conventional idea of herd immunity is based on efficient transmission of pathogens and developing natural immunity within a population.

Effect of N-terminal poly histidine-tag on immunogenicity of Streptococcus pneumoniae surface protein SP0845.

SP0845, a pneumococcal surface protein and a potential candidate vaccine for Streptococcus pneumoniae infection, was used to evaluate the role of histidine affinity tag on its biophysical properties and immunogenicity. The protein was expressed in E. coli with and without histidine affinity tag and purified to homogeneity.

Modulation of immune response and enhanced clearance of Salmonella typhi by delivery of Vi polysaccharide conjugate using PLA nanoparticles.

Polysaccharide antigens do not promote antibody class switching and memory antibody response, thus require conjugation with a T cell dependent carrier protein to generate protective immune response. The intensity of immune responses varies with the carrier proteins for the same carbohydrate antigen and most of the carrier proteins do not generate strong immune responses. Vi polysaccharide and r-flagellin of Salmonella typhi were conjugated and formulated in PLA particles as nanoglycoconjugate which not only generated strong immune response but also promoted antibody class switching and elicited memory antibody response from single point immunization.

Hyaluronic acid - dihydroartemisinin conjugate: Synthesis, characterization and in vitro evaluation in lung cancer cells.

In recent years, a great deal of attention has been given towards re-purposing and re-innovating the potential drugs. In this regard, dihydroartemisinin (DHA) has been reported to demonstrate anti-proliferative effects on various cancerous cells viz. breast, liver and lung.

Curcumin-Artesunate Based Polymeric Nanoparticle; Antiplasmodial and Toxicological Evaluation in Murine Model.

Mainstay chemotherapy for malaria is often faced with the problem of instability and poor bio-distribution thus resulting in impaired pharmacokinetics. Nanomedicine has been acclaimed for its success in drug delivery and improved efficacy. The aim of the study was to assess the antiplasmodial efficacy and safety of curcumin-artesunate co-entrapped nanoparticle in mice model.

Poly(D,L-lactic-co-glycolic acid)-based artesunate nanoparticles: formulation, antimalarial and toxicity assessments.

Objective: The aim of this study was to formulate polymer-based artesunate nanoparticles for malaria treatment.

Methods: Artesunate was loaded with poly(D,L-lactic-co-glycolic acid) (PLGA) by solvent evaporation from an oil-in-water single emulsion. Nanoparticles were characterized by X-ray diffraction and differential scanning calorimetry analyses.

In vitro ovicidal activity of poly lactic acid curcumin-nisin co-entrapped nanoparticle against Fasciola spp. eggs and its reproductive toxicity.

Background: Curcumin and nisin have been widely reported for their antibacterial and anticancer potency. However, their therapeutic applications are hampered by several factors, which necessitate their development into nanosize ranges for improved delivery and activities. Their incorporation into a single nanosynthesized form may suggest desirable efficacy on parasites.

Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles.

Curcumin is a polyphenolic pigment isolated from the rhizomes of (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles.

Nanocurcumin is superior to native curcumin in preventing degenerative changes in Experimental Cerebral Malaria.

Curcumin has many pharmacological activities despite its poor bioavailability and in vivo stability. Here, we show that a nanoformulated curcumin (PLGA-curcumin) has better therapeutic index than native curcumin in preventing the onset of neurological symptoms and delaying the death of mice in experimental cerebral malaria. Oral PLGA-curcumin was at least as effective as native curcumin at a 15-fold lower concentration in preventing the breakdown of blood-brain barrier and inhibition of brain mRNAs for inflammatory cytokines, chemokine receptor CXCR3 and its ligand CXCL10, with an increase in the anti-inflammatory cytokine IL-10.

Inhalable Particles for "Pincer Therapeutics" Targeting Nitazoxanide as Bactericidal and Host-Directed Agent to Macrophages in a Mouse Model of Tuberculosis.

Nitazoxanide (NTZ) has moderate mycobactericidal activity and is also an inducer of autophagy in mammalian cells. High-payload (40-50% w/w) inhalable particles containing NTZ alone or in combination with antituberculosis (TB) agents isoniazid (INH) and rifabutin (RFB) were prepared with high incorporation efficiency of 92%. In vitro drug release was corrected for drug degradation during the course of study and revealed first-order controlled release.

Preparation and Preclinical Evaluation of Inhalable Particles Containing Rapamycin and Anti-Tuberculosis Agents for Induction of Autophagy.

Purpose: Mycobacterium tuberculosis (Mtb) inhibits host defense mechanisms, including autophagy. We investigated particles containing rapamycin (RAP) alone or in combination with isoniazid (INH) and rifabutin (RFB) for: targeting lung macrophages on inhalation; inducing autophagy; and killing macrophage-resident Mtb and/or augmenting anti-tuberculosis (TB) drugs.

Methods: PLGA and drugs were spray-dried.

Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria.

Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15-20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed.

Formulation and characterization of clozapine and risperidone co-entrapped spray-dried PLGA nanoparticles.

In the current study, polylactide-co-glycolide (PLGA) nanoparticles entrapping both clozapine (CLZ) and risperidone (RIS) were formulated by spray-drying using Buchi Nano Spray Dryer B-90 (Flawil, Switzerland). Parameters such as inlet temperature, spray mesh diameter, sample flow rate, spray rate and applied pressure were optimized to produce nanoparticles having desired release profile using both low- and high-molecular weight PLGA polymer. Smallest size nanoparticle of size around 248 nm could be prepared using a 4.

Asparagus racemosus competitively inhibits in vitro the acetylcholine and monoamine metabolizing enzymes.

Asparagus racemosus (AR) has earlier been reported to possess antidepressant activity possibly mediated through the monoaminergic system, and nootropic and anti amnestic activities possibly through the cholinergic system. In the present study to further understand the mechanism of action, we evaluated the kinetics of acetyl (AChE) and butyryl (BuChE) cholinesterases, and monoamine oxidase (MAO-A and B) enzyme inhibitory activities of different fractions of AR. The results showed that methanolic extract of AR (MAR) significantly inhibited cholinesterase and MAO activities as compared to hexane (HAR) and chloroform (CAR) extracts of AR as evident from the IC(50) values.