"Novel mucoadhesive PLGA-PVM/MA micro-nanocomposites loaded with felodipine intended for pulmonary administration by nebulization".

Poly(latic-co-glycolic) acid (PLGA) nanoparticles loaded with felodipine (FEL) were embedded in a mucoadhesive matrix of poly (methyl vinyl ether-co-maleic anhydride) (PVM/MA) to prepare micro-nanoparticulate composites by particle engineering. Composites were characterized for physical and rheological properties and formulated with inhalable grade lactose. In-vitro characterization studies such as drug release kinetics, and mucoadhesive, and aerodynamic properties were performed.

Tailoring Chlorthalidone Aqueous Solubility by Cocrystallization: Stability and Dissolution Behavior of a Novel Chlorthalidone-Caffeine Cocrystal.

A cocrystal of the antihypertensive drug chlorthalidone (CTD) with caffeine (CAF) was obtained (CTD-CAF) by the slurry method, for which a 2:1 stoichiometric ratio was found by powder and single-crystal X-ray diffraction analysis. Cocrystal CTD-CAF showed a supramolecular organization in which CAF molecules are embedded in channels of a 3D network of CTD molecules. The advantage of the cocrystal in comparison to CTD is reflected in a threefold solubility increase and in the dose/solubility ratios, which diminished from near-unit values for to 0.

Nanoconfinement of a Pharmaceutical Cocrystal with Praziquantel in Mesoporous Silica: The Influence of the Solid Form on Dissolution Enhancement.

Nanoconfinement is a recent strategy to enhance solubility and dissolution of active pharmaceutical ingredients (APIs) with poor biopharmaceutical properties. In this work, we combine the advantage of cocrystals of racemic praziquantel (PZQ) containing a water-soluble coformer (i.e.

Dissolution Advantage of Nitazoxanide Cocrystals in the Presence of Cellulosic Polymers.

The effect of hydroxypropyl methylcellulose (HPMC) and methylcellulose (Methocel 60 HG) on the dissolution behavior of two cocrystals derived from nitazoxanide (NTZ), viz., nitazoxanide-glutaric acid (NTZ-GLU, 1:1) and nitazoxanide-succinic acid (NTZ-SUC, 2:1), was explored. Powder dissolution experiments under non-sink conditions showed similar dissolution profiles for the cocrystals and pure NTZ.

Interrelation of the dissolution behavior and solid-state features of acetazolamide cocrystals.

The thermal behavior, phase stability, indicative stability and intrinsic dissolution rates of a series of cocrystals and cocrystal hydrates derived from the pharmaceutically active ingredient acetazolamide (ACZ) and 2-aminobenzamide (2ABAM), 2,3-dihydroxybenzoic acid (23DHBA), 2-hydroxybenzamide (2HBAM), 4-hydroxybenzoic acid (4HBA), nicotinamide (NAM) and picolinamide (PAM) as cocrystal formers have been evaluated. Upon heating in an inert atmosphere most of the cocrystals tested demonstrated first the elimination of the crystal former, followed by ACZ degradation. Only in cocrystals with NAM was melting observed.

Sulfonate salts of the therapeutic agent dapsone: 4-[(4-aminophenyl)sulfonyl]anilinium benzenesulfonate monohydrate and 4-[(4-aminophenyl)sulfonyl]anilinium methanesulfonate monohydrate.

Dapsone, formerly used to treat leprosy, now has wider therapeutic applications. As is the case for many therapeutic agents, low aqueous solubility and high toxicity are the main problems associated with its use. Derivatization of its amino groups has been widely explored but shows no significant therapeutic improvements.

Enhanced cellular uptake and gene silencing activity of siRNA molecules mediated by chitosan-derivative nanocomplexes.

The RNA interference (RNAi) constitutes a conservative mechanism in eukaryotic cells that induces silencing of target genes. In mammalians, the RNAi is triggered by siRNA (small interfering RNA) molecules. Due to its potential in silencing specific genes, the siRNA has been considered a potential alternative for the treatment of genetic and acquired diseases.

Design and in vitro evaluation of a new nano-microparticulate system for enhanced aqueous-phase solubility of curcumin.

Curcumin, a yellow polyphenol derived from the turmeric Curcuma longa, has been associated with a diverse therapeutic potential including anti-inflammatory, antioxidant, antiviral, and anticancer properties. However, the poor aqueous solubility and low bioavailability of curcumin have limited its potential when administrated orally. In this study, curcumin was encapsulated in a series of novel nano-microparticulate systems developed to improve its aqueous solubility and stability.

Formulation approaches to short interfering RNA and MicroRNA: challenges and implications.

RNA interference has emerged as a potentially powerful tool in the treatment of genetic and acquired diseases by delivering short interfering RNA (siRNA) or microRNA (miRNA) to target genes, resulting in their silencing. However, many physicochemical and biological barriers have to be overcome to obtain efficient in vivo delivery of siRNA and miRNA molecules to the organ/tissue of interest, thereby enabling their effective clinical therapy. This review discusses the challenges associated with the use of siRNA and miRNA and describes the nonviral delivery strategies used in overcoming these barriers.

A Novel Aerosol Method for the Production of Hydrogel Particles.

A novel method of generating hydrogel particles for various applications including drug delivery purposes was developed. This method is based on the production of hydrogel particles from sprayed polymeric nano/microdroplets obtained by a nebulization process that is immediately followed by gelation in a crosslinking fluid. In this study, particle synthesis parameters such as type of nebulizer, type of crosslinker, air pressure, and polymer concentration were investigated for their impact on the mean particle size, swelling behavior, and morphology of the developed particles.

Risks and benefits of commonly used herbal medicines in Mexico.

In Mexico, local empirical knowledge about medicinal properties of plants is the basis for their use as home remedies. It is generally accepted by many people in Mexico and elsewhere in the world that beneficial medicinal effects can be obtained by ingesting plant products. In this review, we focus on the potential pharmacologic bases for herbal plant efficacy, but we also raise concerns about the safety of these agents, which have not been fully assessed.

The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in transiently transfected COS-7 cells.

Recently, the expression of the human peptide/histidine transporter (hPHT1, SLC15A4) mRNA was observed in the GI tract and in Caco-2 cells, suggesting that it may participate in the intestinal absorption of peptide-based agents. This study aims to elucidate the: (i) protein expression pattern of hPHT1 (SLC15A4) in human small intestine; (ii) cloning of the hPHT1 full-length sequence; (iii) functional characterization of hPHT1 in transiently transfected COS-7 cells. The expression of hPHT1 was measured using Western blot and immunohistochemical analysis.

Expression of multiple drug resistance conferring proteins in normal Chinese and Caucasian small and large intestinal tissue samples.

Multidrug resistance conferring proteins (MDRCP) are ATP-binding cassette (ABC) transporters known to significantly influence the absorption, distribution, metabolism, and elimination (ADME) and toxic behavior of many therapeutic agents. Research in the pharmacogenomics area has suggested that mutations and variable expression patterns of these MDCRPs may exist in tissue samples from different ethnic groups. The goal of this study was to examine the expression of P-glycoprotein (PGP), sister of PGP (S-PGP), multidrug resistance protein 3 (Mdr3), multidrug resistance like proteins 1-5 (MRP 1-5), and lung resistance associated protein (LRP) in tissue slides and protein lysates derived from normal adult small or large intestines of Caucasian or Chinese origin.

Delineation of human peptide transporter 1 (hPepT1)-mediated uptake and transport of substrates with varying transporter affinities utilizing stably transfected hPepT1/Madin-Darby canine kidney clones and Caco-2 cells.

In the present investigation, the uptake and transport kinetics of valacyclovir (VACV), 5-aminolevulinic acid (5-ALA), and benzylpenicillin (BENZ) were studied in stably transfected Madin-Darby canine kidney (MDCK)/human peptide transporter 1 (hPepT1)-V5&His clonal cell lines expressing varying levels of epitope-tagged hPepT1 protein (low, medium, and high expression) and in Caco-2 cells to delineate hPepT1-mediated transport kinetics. These compounds were selected due to the fact that they are known PepT1 substrates, yet also have affinity for other transporters. Caco-2 cells, traditionally used for studying peptide-based drug transport, were included for comparison purposes.

A novel hPepT1 stably transfected cell line: establishing a correlation between expression and function.

Stably transfected MDCK/hPepT1-V5&His clonal cell lines expressing varying levels of epitope-tagged hPepT1 protein were established to quantify the relationship between transgene hPepT1 expression levels and its functional kinetics in facilitating peptide and peptide-like drug uptake and transport in vitro. The hPepT1 sequence was amplified from Caco-2 cell mRNA, inserted into the pcDNA3.1 -V5&His TOPO plasmid, and transfected into MDCK cells.

Current perspectives on established and putative mammalian oligopeptide transporters.

Peptides and peptide-based drugs are increasingly being utilized as therapeutic agents for the treatment of numerous disorders. The increasing development of peptide-based therapeutic agents is largely due to technological advances including the advent of combinatorial peptide libraries, peptide synthesis strategies, and peptidomimetic design. Peptides and peptide-based agents have a broad range of potential clinical applications in the treatment of many disorders including AIDS, hypertension, and cancer.