Physicochemical Properties, Drug Release and In Situ Depot-Forming Behaviors of Alginate Hydrogel Containing Poorly Water-Soluble Aripiprazole.

The objective of this study was to investigate the physicochemical properties, drug release and in situ depot-forming behavior of alginate hydrogel containing poorly water-soluble aripiprazole (ARP) for achieving free-flowing injectability, clinically accessible gelation time and sustained drug release. The balanced ratio of pyridoxal phosphate (PLP) and glucono-delta-lactone (GDL) was crucial to modulate gelation time of the alginate solution in the presence of calcium carbonate. Our results demonstrated that the sol state alginate hydrogel before gelation was free-flowing, stable and readily injectable using a small 23 G needle.

Polyelectrolyte-based solid dispersions for enhanced dissolution and pH-Independent controlled release of sildenafil citrate.

The aim of this study was to design a novel matrix tablet with enhanced dissolution and pH-independent controlled release of sildenafil citrate (SIL), a drug with pH-dependent solubility, by using solid dispersions (SDs) and polyelectrostatic interactions. SIL-loaded SDs were prepared using various polymeric carriers such as poloxamer 188, poloxamer 407, Soluplus®, polyvinylpyrrolidone (PVP) K 12, and PVP K 17 by the solvent evaporation method. Among these polymers, Soluplus® was found to be the most effective in SDs for enhancing the drug dissolution over 6 h in pH 6.

The angiotensin receptor neprilysin inhibitor LCZ696 attenuates renal fibrosis via ASK1/JNK/p38 MAPK-mediated apoptosis in unilateral ureteral obstruction.

The angiotensin receptor neprilysin inhibitor LCZ696 affords superior cardioprotection and renoprotection compared with renin-angiotensin blockade monotherapy, but the underlying mechanisms remain elusive. Herein, we evaluated whether LCZ696 attenuates renal fibrosis by inhibiting ASK1/JNK/p38 mitogen-activated protein kinase (MAPK)-mediated apoptosis in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Rats with UUO were treated daily for 7 days with LCZ696, valsartan, or the selective ATP competitive inhibitor of apoptosis signal-regulating kinase 1 (ASK1), GS-444217.

Development of a new rapid, economical and eco-friendly HPLC method for in vitro and in vivo determination of zolmitriptan.

Multiple high-performance liquid chromatographic (HPLC) approaches have been briefly defined for the assessment of zolmitriptan (ZMT). These methods are either cumbersome or require a plentiful volume of organic solvents, thus offering extortionate procedures. The objective of this study was to establish and validate a new rapid, eco- friendly and cost-effective HPLC method for the analysis of ZMT.

Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box-Behnken Experimental Design.

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40-45%) due to the hepatic metabolism.

Design and evaluation of in vivo bioavailability in beagle dogs of bilayer tablet consisting of immediate release nanosuspension and sustained release layers of rebamipide.

The purpose of this study was to develop a once-daily, bilayer matrix tablet with immediate (IR) and sustained release (SR) layers of poorly water-soluble and absorption site dependent rebamipide (RBM) to substitute three times a day IR tablet. Owing to the pH-dependent poor water solubility of RBM in low pH condition, salt-caged nanosuspensions (NSPs) consisting of RBM and poloxamer 407 (POX 407) or poloxamer 188 (POX 188) were prepared using an acid-base neutralization method to increase the dissolution rate, which was subsequently applied to the immediate-release (IR) layer. Polyethylene oxide (PEO) with different molecular weights (PEO 100,000 and PEO 5,000,000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were then investigated as SR agents to incorporate into the SR layer with pure RBM via wet granulation method.

Electrostatic molecular effect of differently charged surfactants on the solubilization capacity and physicochemical properties of salt-caged nanosuspensions containing pH-dependent and poorly water-soluble rebamipide.

In this study, the electrostatic molecular effect of differently charged surfactants on the solubilization capacity and physicochemical properties of salt-caged nanosuspensions (NSPs) containing poorly water-soluble drug was investigated. Anionic rebamipide (RBM) was chosen as a model drug because of its poor water solubility in low pH condition and ionizable acidic forms. Negatively charged sodium lauryl sulfate (SLS) and positively charged cetyltrimethylammonium bromide (CTAB) were selected as surfactants for the preparation of NSPs or in the dissolution medium.

Biomacromolecule-mediated pulmonary delivery of siRNA and anti-sense oligos: challenges and possible solutions.

Biomacromolecules have gained much attention as biomedicine carriers in recent years due to their remarkable biophysical and biochemical properties including sustainability, non-toxicity, biocompatibility, biodegradability, long systemic circulation time and ability to target. Recent developments in a variety of biological functions of biomacromolecules and progress in the study of biological drug carriers suggest that these carriers may have advantages over carriers of synthetic materials in terms of half-life, durability, protection and manufacturing facility. Despite the full pledge advancements in the applications of biomacromolecules, its clinical use is hindered by certain factors that allow the pre-mature release of loaded cargos before reaching the target site.

Role of Surfactant Micellization for Enhanced Dissolution of Poorly Water-Soluble Cilostazol Using Poloxamer 407-Based Solid Dispersion via the Anti-Solvent Method.

This study aimed to investigate the role of micellization of sodium lauryl sulfate (SLS) in poloxamer 407 (POX)-based solid dispersions (POX-based SDs) using the anti-solvent method in enhancing the dissolution rate of practically water-insoluble cilostazol (CLT). Herein, SLS was incorporated into CLT-loaded SDs, at a weight ratio of 50:50:10 of CLT, POX, and SLS by three different methods: anti-solvent, fusion (60 °C), and solvent (ethanol) evaporation. The SDs containing micellar SLS in the anti-solvent method were superior in the transformation of the crystalline form of the drug into a partial amorphous state.

Luteolin and cancer metastasis suppression: focus on the role of epithelial to mesenchymal transition.

Epithelial to mesenchymal transition (EMT) is a physiological process that assumes a primary role in the induction of cancer metastasis. This results in increased cell renewal, and resistance to cell death and therapies. EMT, therefore, represents an effective strategy for regulating cancerous cell activity.

Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues.

Novel collagenase IV (ColIV) and clusterin (CLU)-modified polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles that load doxorubicin (DOX) were designed and fully evaluated and . PCL-PEG-ColIV was synthesized by linking PCL-PEG and ColIV through a carbodiimide method. DOX-loaded nanoparticles (DOX-PCL-PEG-ColIV) were self-assembly prepared, followed by noncovalently adsorbing CLU on the DOX-PCL-PEG-ColIV surface to obtain DOX-PCL-PEG-ColIV /CLU nanoparticles, which can penetrate through the tumor extracellular matrix (ECM) and inhibit phagocytosis by macrophage.

Fatty acid chain length impacts nanonizing capacity of albumin-fatty acid nanomicelles: Enhanced physicochemical property and cellular delivery of poorly water-soluble drug.

This study aimed to design the ideal nanonizing vehicle for poorly water-soluble model curcumin (CCM) using fattigation-platform nanotechnology, and to investigate the effects of fatty acid salts chain length on nanonizing CCM and its efficient delivery to different cancer cells. HSA-fatty acid conjugates were synthesized by EDC/NHS coupling. Fattigation-platform nanomicelles (NMs), prepared by film hydration, exhibited uniform and spherical morphology, although, each NM varied in particle size, zeta potential, and critical micelle concentration according to the types of fatty acid.

Combinatory interpretation of protein corona and shear stress for active cancer targeting of bioorthogonally clickable gelatin-oleic nanoparticles.

Nanoparticle-protein interactions under conditions mimicking physiology determine how nanoparticles (NPs) will behave inside blood vessels and, therefore, the overall outcome of the drug-delivery system. Here, for the first time, we explore the effects of bio-mimicking shear stress and protein corona conditions on novel active targeting of clickable fattigation nanoparticles (NPs) for cancer therapy. Active targeting dibenzocyclooctyne-functionalized biocompatible gelatin-oleic NPs (GON-DBCOs) via a bioorthogonal click reaction were prepared by the desolvation method for delivery of docetaxel (DTX) to lung and breast cancer models.

Investigation of Crystallization and Salt Formation of Poorly Water-Soluble Telmisartan for Enhanced Solubility.

The crystal changes and salt formation of poorly water-soluble telmisartan (TEL) in various solvents were investigated for enhanced solubility, stability and crystallinity. Polymorphic behaviors of TEL were characterized by dispersing in distilled water, acetone, acetonitrile, DMSO, or ethanol using Method I: without heat and then dried under vacuum at room temperature; and Method II: with heat below boiling temperature, cooled at 5 °C, and then dried under vacuum at 40 °C. For salt formation (Method III), the following four powdered mixtures were prepared by dispersing in solution of hydrochloric acid (HCl) (pH 1.

Enhanced Lysosomal Escape of pH-Responsive Polyethylenimine-Betaine Functionalized Carbon Nanotube for the Codelivery of Survivin Small Interfering RNA and Doxorubicin.

The combination of gene therapy and chemotherapy has recently received considerable attention for cancer treatment. However, low transfection efficiency and poor endosomal escape of genes from nanocarriers strongly limit the success of the clinical use of small interfering RNA (siRNA). In this study, a novel pH-responsive, surface-modified single-walled carbon nanotube (SWCNT) was designed for the codelivery of doxorubicin (DOX) and survivin siRNA.

Design and evaluation of clickable gelatin-oleic nanoparticles using fattigation-platform for cancer therapy.

The principles of bioorthogonal click chemistry and metabolic glycoengineering were applied to produce targeted anti-cancer drug delivery via fattigation-platform-based gelatin-oleic nanoparticles. A sialic acid precursor (AcManNAz) was introduced to the cell surface. Gelatin and oleic acid were conjugated by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) chemistry with the subsequent covalent attachment of dibenzocyclooctyne (DBCO) in a click reaction on the cell surface.

Effective deactivation of A549 tumor cells in vitro and in vivo by RGD-decorated chitosan-functionalized single-walled carbon nanotube loading docetaxel.

This study aims to construct and evaluate RGD-decorated chitosan (CS)-functionalized pH-responsive single-walled carbon nanotube (SWCNT) carriers using docetaxel (DTX) as a model anticancer drug. DTX was loaded onto SWCNT via π-π stacking interaction (SWCNT-DTX), followed by the non-covalent conjugation of RGD-decorated CS to SWCNT-DTX to prepare RGD-CS-SWCNT-DTX. The RGD-CS-SWCNT-DTX showed significantly higher drug release than the pure drug, giving higher release rate at pH 5.

Design of fixed dose combination and physicochemical characterization of enteric-coated bilayer tablet with circadian rhythmic variations containing telmisartan and pravastatin sodium.

The aim of this study was to investigate a fixed dose combination (FDC) of telmisartan (TEL) and pravastatin sodium (PRA) in enteric-coated bilayer tablets, which was designed for once-daily bedtime dose in order to match circadian rhythmic variations of hypertension and cholesterol synthesis and optimize the patient friendly dosing treatment. Due to the poor aqueous solubility of TEL, ternary solid dispersions (SD) consisting of TEL, polyethylene glycol 6000 (PEG 6000) and magnesium oxide (MgO) were designed to enhance its dissolution rate in intestinal fluid. MgO was added as an effective alkalizer to maintain the high microenvironmental pH of the saturated solution in the immediate vicinity of TEL particles because TEL is known to be ionizable but poorly soluble in intestinal fluid.

In-Vitro Characterization and Oral Bioavailability of Organic Solvent-free Solid Dispersions Containing Telmisartan.

Poorly water-soluble drugs often suffer from limited or irreproducible clinical response due to their low solubility and dissolution rate. In this study, organic solvent-free solid dispersions (OSF-SDs) containing telmisartan (TEL) were prepared using polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 6000 (PEG 6000) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant by a lyophilization method. In-vitro dissolution rate and physicochemical properties of the OSF-SDs were characterized using the USP I basket method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and fourier transform-infrared (FT-IR) spectroscopy.

Gastrointestinal stability, physicochemical characterization and oral bioavailability of chitosan or its derivative-modified solid lipid nanoparticles loading docetaxel.

Objective: The purpose of this study was to prepare the positively charged chitosan (CS)- or hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) loading docetaxel (DTX), and to evaluate their properties in vitro and in vivo.

Methods: The DTX-loaded SLNs (DTX-SLNs) were prepared through an emulsion solvent evaporation method and further modified with CS or HACC (CS-DTX-SLNs or HACC-DTX-SLNs) via noncovalent interactions. The gastrointestinal (GI) stability, dissolution rate, physicochemical properties and cytotoxicities of SLNs were investigated.

Positively Charged Surface-Modified Solid Lipid Nanoparticles Promote the Intestinal Transport of Docetaxel through Multifunctional Mechanisms in Rats.

Solid lipid nanoparticles (SLNs) are one of the most promising nanocarriers to increase the oral absorption of drugs with poor solubility and low permeability. However, the absorption mechanism of SLNs remains incomplete and thus requires further careful consideration. In this study, positively charged chitosan (CS) modified SLNs or hydroxypropyl trimethylammonium chloride chitosan (HACC) modified SLNs were designed and their absorption mechanisms were fully clarified to improve the oral absorption of docetaxel (DTX).

Effect of biomimetic shear stress on intracellular uptake and cell-killing efficiency of doxorubicin in a free and liposomal formulation.

Shear stress could be considered in the context of cellular uptake and cell-killing efficiency. Thus, mimicking the dynamic characteristics of in vivo environment is important in targeted drug delivery. We investigated the intracellular uptake and cell-killing efficiency of doxorubicin (DOX) in a free and liposomal form (Doxil(®)) under biomimetic shear stress to mimic in vivo environment.

pH-dependent release of platycodin mitigates its gastrointestinal mucosa irritation after oral administration in rats.

The present study aimed to evaluate the gastrointestinal mucosa irritation of three platycodin formulations. Platycodin-loaded core pellets were prepared via extrusion-spheronization method and coated with Eudragit(®) L100-55 (L100) or Eudragit(®) S100 (S100) for pH-dependent release. The release of platycodin D from coated pellets exhibited pH dependent release profiles.

Optimization of process variables of zanamivir-loaded solid lipid nanoparticles and the prediction of their cellular transport in Caco-2 cell model.

The aim of this study was to optimize the process variables of zanamivir-loaded solid lipid nanoparticles (SLNs) and to predict their cellular transport across Caco-2 cell monolayers. Zanamivir-loaded SLNs were prepared by a double emulsion solvent evaporation method. The effects of process variables on the mean particle size and zeta potential of SLNs were investigated and the physicochemical properties of SLNs were characterized.