Oral In-Situ Nanoplatform with Balanced Hydrophobic-Hydrophilic Property for Transport Across Gastrointestinal Mucosa.

Transport of oral nanocarriers across the GI epithelium necessitates transport across hydrophilic mucus layer and the hydrophobic epithelium. Based on hydrophobic-hydrophilic balance, Curcumin-Lipomer (lipid-polymer hybrid nanoparticles) comprising hydrophobic stearic acid and hydrophilic Gantrez™ AN 119 (Gantrez) were developed, by a radical in-situ approach, to successfully traverse both barriers. A monophasic preconcentrate (Cur-Pre) comprising Cur (Curcumin), stearic acid, Gantrez and stabilizers, prepared by simple solution, was added to an aqueous phase to instantaneously generate Curcumin-Lipomer (Cur-Lipo) of nanosize and high entrapment efficiency (EE).

Polydispersity-mediated high efficacy of an in-situ aqueous nanosuspension of PPEF.3HCl in methicillin resistant Staphylococcus aureus sepsis model.

Recently, World Health Organization declared antimicrobial resistance as the third greatest threat to human health. Absence of known cross-resistance, new class, new target, and a new mode of action are few major strategies being undertaken by researches to combat multidrug resistant pathogen. PPEF.

Macrophage targeted polymeric curcumin nanoparticles limit intracellular survival of through induction of autophagy and augment anti-TB activity of isoniazid in RAW 264.7 macrophages.

Rapid emergence of antibiotic resistance in tuberculosis has left us with limited resources to treat and manage multi drug resistant (MDR) cases of tuberculosis, prompting the development of novel therapeutics. (MTB) perturbs the host protective pathways for its survival, therefore host directed therapeutic (HDT) interventions offer an attractive alternative strategy. Curcumin (CMN), the principle curcuminoid from is known to have anti-TB activity against MDR strains of MTB in macrophages.

Nano Drug Delivery Strategies for an Oral Bioenhanced Quercetin Formulation.

Quercetin, a naturally occurring flavonoid, has been credited with a wide spectrum of therapeutic properties. However, the oral use of quercetin is limited due to its poor water solubility, low bioavailability, rapid metabolism, and rapid plasma clearance. Quercetin has been studied extensively when used with various nanodelivery systems for enhancing quercetin bioavailability.

pH-responsive microparticles of rifampicin for augmented intramacrophage uptake and enhanced antitubercular efficacy.

In this study we present pH-responsive rifampicin (RIF) microparticles comprising lecithin and a biodegradable hydrophobic polymer, polyethylene sebacate (PES), to achieve high intramacrophage delivery and enhanced antitubercular efficacy. PES and PES-lecithin combination microparticles (PL MPs) prepared by single step precipitation revealed average size of 1.5 to 2.

Facile Technology for Extemporaneous Preparation of Long-Acting Injectable Microparticulate Suspensions at the Patient Side.

In this study, we present an innovative and facile in situ approach for extemporaneous preparation of sterile microparticles. An amazingly simple approach, in situ technology circumvents the stability, and scale up challenges as well as sterilization issues associated with long-acting particulate systems. Monophasic preconcentrates of donepezil base (DPZ), a model drug with a biodegradable polymer poly (DL-lactide-co-glycolide) (PLGA), with stabilizer were prepared by simple solution and sterilized by filtration (0.

In-silico approach as a tool for selection of excipients for safer amphotericin B nanoformulations.

Safer and efficacious Amphotericin B (AmB) nanoformulations can be designed by augmenting AmB in the monomeric or super-aggregated state, and restricting the aggregated state, by choosing the appropriate excipient, which can be facilitated by employing in-silico prediction as a tool. Excipients selected for the study included linear fatty acids from caprylic (C) to stearic(C) and the stearate based amphiphilic surfactants polyoxyl-15-hydroxystearate (PS15) and polyoxyl-40-stearate (PS40). Blend module was employed to determine the two miscibility parameters mixing energy (E) and interaction parameter (χ).

Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer's Disease.

Polyunsaturated fatty acids (PUFAs) are a class of fatty acids that are closely associated with the development and function of the brain. The most abundant PUFA is docosahexaenoic acid (DHA, 22:6 -3). In humans, low plasmatic concentrations of DHA have been associated with impaired cognitive function, low hippocampal volumes, and increased amyloid deposition in the brain.

Development and Optimization of Microballoons Assisted Floating Tablets of Baclofen.

The objective of the present study was to develop microballoons aided gastro-retentive floating tablets of baclofen, a skeletal muscle relaxant with a low elimination half-life of ~ 3.5 h. Baclofen floating tablet was prepared to offer convenience by designing a tablet that would float in the stomach for a prolonged period and allow controlled drug release to enable once-a-day administration.

An innovative approach using microencapsulated turmeric oleoresin to develop ready-to-use turmeric milk powder with enhanced oral bioavailability.

The use of phytochemicals for nutritional wellness has attracted worldwide attention and resulted in development of innovative formulations. Turmeric latte is one such formulation. However, an in-depth study on its physicochemical properties and oral bioavailability has not been conducted as yet.

Enhanced Antibacterial Activity of Doxycycline and Rifampicin Combination Loaded in Nanoparticles against Intracellular .

Introduction: Brucellosis is a zoonotic disease that is prevalent in livestock animals. The bacteria reside inside the macrophage cells of the host. The WHO has endorseda combination treatment therapy for brucellosis against the conventional monotherapy to avoid relapse and resistance.

Innovative Betulin Nanosuspension exhibits enhanced anticancer activity in a Triple Negative Breast Cancer Cell line and Zebrafish angiogenesis model.

We present a nanosuspension of betulin, a BCS class II anticancer drug, particularly effective against resistant breast cancer. As anticancer efficacy of betulin is hampered by poor aqueous solubility, a nanosuspension with surface area was considered to enhance efficacy. An innovative approach wherein the betulin nanosuspension is generated instantaneously in situ, by adding a betulin preconcentrate (BeTPC) comprising drug and excipients, to aqueous medium, is successfully demonstrated.

Pre-clinical evaluation of an innovative oral nano-formulation of baicalein for modulation of radiation responses.

There is an unmet medical need for non-toxic and effective radiation countermeasures for prevention of radiation toxicity during planned exposures. We have earlier shown that intraperitoneal administration of baicalein (BCL) offers significant survival benefit in animal model. Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of baicalein has been reported in pre-clinical model systems and also in healthy human volunteers.

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19.

The global pandemic of Coronavirus Disease 2019 (COVID-19) has brought the world to a grinding halt. A major cause of concern is the respiratory distress associated mortality attributed to the cytokine storm. Despite myriad rapidly approved clinical trials with repurposed drugs, and time needed to develop a vaccine, accelerated search for repurposed therapeutics is still ongoing.

Nose-to-Brain Delivery of Diazepam from an Intranasal Aqua-Triggered In-Situ (ATIS) Gelling Microemulsion: Monitoring Brain Uptake by Microdialysis.

Background And Objectives: An innovative intranasal aqua-triggered in-situ (ATIS) gel is a polymer-free in-situ gelling microemulsion which gels instantaneously on contact with minute quantities of water to form a mucoadhesive gel. The objective of the study was to develop ATIS diazepam (ATIS-diazepam) as an alternative to the injection for epileptic emergencies and evaluate its brain uptake and nose-to-brain targeting efficiency in rats.

Methods: ATIS-diazepam (1 mg/100 µL) was prepared and characterized for in vitro formulation characteristics.

Enhancing Safety and Efficacy by Altering the Toxic Aggregated State of Amphotericin B in Lipidic Nanoformulations.

The toxicity of Amphotericin B (AmB) is contributed by the small, water-soluble aggregates of the drug. Hence, AmB lipid polymer hybrid nanoparticles (LIPOMER), comprising stearate lipids with a hydrophilic polymer Gantrez (GZ), and solid lipid nanoparticles (SLN), comprising only stearates, were prepared with the objective of monomerizing AmB. While intercalation of stearates with the hydrophobic polyene chain could hinder AmB-AmB interactions, enabling monomerization, it was hypothesized that GZ could aid in the stabilization of the monomers through hydrophilic interactions.

Intramacrophage Delivery of Dual Drug Loaded Nanoparticles for Effective Clearance of Mycobacterium tuberculosis.

The escalating global burden of tuberculosis necessitates radical strategies to curb its spread. In this study, rifampicin (RIF), a first line anti-tubercular antibiotic and curcumin (CUR), a promising antimycobacterial compound were co-encapsulated in polymeric nanoparticles to achieve intramacrophage delivery and improved Mycobacterium tuberculosis clearance. The dual loaded nanoparticles revealed average size ∼400 nm, low polydispersity and zeta potential of -26.

Fabrication of gelatin functionalized silver nanoparticles for blood group profiling.

We report the fabrication of silver nanoparticles (AgNPs) surface functionalized with gelatin at different concentrations (G10/G20/G40 AgNPs) with an average particle size of ∼200 nm, bioconjugated with antisera antibodies (AsAbs) of the major and clinically significant blood groups (CSBGs) at different titres from neat to 1:128. Bioconjugation using ionic interaction at pH 7.4 enabled 'end-on' configuration, with the -NH2 group of the antibody free for interaction with the red blood cell antigen, as confirmed by Fourier transform infrared spectroscopy.

Bone targeted delivery of salmon calcitonin hydroxyapatite nanoparticles for sublingual osteoporosis therapy (SLOT).

We present salmon calcitonin (SCT) loaded Hydroxyapatite nanoparticles (HAP-NPs) for sublingual osteoporosis therapy. Surface stabilized HAP-NPs were prepared by aqueous precipitation. SCT was loaded by ionic complexation, as confirmed by FTIR.

Shape mediated splenotropic delivery of buparvaquone loaded solid lipid nanoparticles.

Buparvaquone (BPQ)-loaded asymmetric solid lipid nanoparticles (SLN) prepared by a modified nanoprecipitation method were evaluated for splenotropic drug delivery. BPQ SLN exhibited an average particle size of 650.28 ± 6.

Enhancing Curcumin Oral Bioavailability Through Nanoformulations.

Curcumin is a promising therapeutic agent that exhibits manifold therapeutic activities. However, it is challenging to study curcumin as it exhibits poor aqueous solubility and low permeability and it is a substrate for P-glycoprotein (P-gp). It is readily metabolized in the body, but many active metabolites of curcumin have been identified that could also be exploited for therapy.

Polymeric curcumin nanoparticles by a facile in situ method for macrophage targeted delivery.

Targeting macrophages is a promising strategy for improved therapy of intracellular infections as macrophages exhibit rapid phagocytosis of particles >200 nm. Entrapment of Curcumin (CUR) in nanocarriers could provide bioenhancement and macrophage targeting. We present a simple and facile nanoprecipitation approach for instantaneous and on-site generation of curcumin nanoparticles (ISCurNP).

Exploring Peyer's Patch Uptake as a Strategy for Targeted Lung Delivery of Polymeric Rifampicin Nanoparticles.

Uptake of nanoparticles through Peyer's Patches following oral administration could enable translocation through lymph to lymphatic organs like the lungs. An important consideration, however, is nanosize and particle hydrophobicity. Furthermore, as delivering the nanoparticles to the intestine where the Peyer's Patches are localized is important, their intact and rapid transit through the stomach into the intestine is highly desirable.

Enhanced antimalalarial activity of a prolonged release in situ gel of arteether-lumefantrine in a murine model.

The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treatment of falciparum malaria. Arteether (ART), an artemisinin derivative, is effective against Plasmodium falciparum, but it is available only as painful oily intramuscular (i.m.