Hyaluronan nanoplatelets exhibit extended residence time compared to spherical and ellipsoidal nanomaterials with equivalent surface potentials and volumes after oral delivery in rats.

The physicochemical properties of colloidal particles-such as size, surface properties, and morphology-play a crucial role in determining their behaviors and transit through the gastrointestinal (GI) tract. While some data exist for nonspherical nanomaterials (NMs) composed of silica or polystyrene, there is limited understanding of NMs composed of polysaccharides and polymers. This study explores the fate and GI tract residence time of hyaluronan-based NMs with distinctive hexagonal morphology and flat surfaces (nanoplatelets) following administration to rats.

A physiologically-based pharmacokinetic model for predicting doxorubicin disposition in multiple tissue levels and quantitative toxicity assessment.

Doxorubicin is a widely-used chemotherapeutic drug, however its high toxicity poses a significant challenge for its clinical use. To address this issue, a physiologically-based pharmacokinetic (PBPK) model was implemented to quantitatively assess doxorubicin toxicity at cellular scale. Due to its unique pharmacokinetic behavior (e.

Exploring the permeability of Amphotericin B trough serum albumin dispersions and lipid nanocarriers for oral delivery.

Amphotericin B (AmB) is a potent polyenic antifungal agent with leishmanicidal activity. Due to its low solubility and permeability in the gastrointestinal tract, AmB is usually administered intravenously. In this context, various approaches have been used to try to improve these properties.

Hyaluronan nanoplatelets exert an intrinsic anti-inflammatory activity in a rat model of bladder painful syndrome/interstitial cystitis.

Glycosaminoglycan (GAG) replenishment therapy consists of the instillation of GAG solutions directly in the bladder to alleviate Bladder Painful Syndrome/Interstitial Cystitis (BPS/IC). However, several issues were reported with this strategy because the GAG solutions are rapidly eliminated from the bladder by spontaneous voiding, and GAG have low bioadhesive behaviors. Herein, GAG nanomaterials with typical flattened morphology were obtained by a self-assembly process.

Shape stability of ellipsoidal nanomaterials prepared by physical deformation.

The nonspherical shape of nanomaterials (NMs) represents a key attribute for controlling their biological behaviors. Analyzing shape stability over time represents a significant concern because nonspherical NMs are likely to rearrange into a thermodynamically more stable spherical shape. In this investigation, ellipsoidal NMs were designed by physical deformation of core/shell nanospheres composed of poly(isobutylcyanoacrylate) and chitosan or a mixture of chitosan and thiolated chitosan.

Real-time visualization of morphology-dependent self-motion of hyaluronic acid nanomaterials in water.

Drug delivery to target sites is often limited by inefficient particle transport through biological media. Herein, motion behaviors of spherical and nonspherical nanomaterials composed of hyaluronic acid were studied in water using real-time multiple particle tracking technology. The two types of nanomaterials have comparable surface compositions and surface potentials, and they have equivalent diameters.

Nanoparticles facing the gut barrier: Retention or mucosal absorption? Mechanisms and dependency to nanoparticle characteristics.

A better knowledge on influence of nanomedicine characteristics on their biological efficacy and safety is expected to accelerate their clinical translation. This work aimed understanding of the oral fate of polymer-based nanomedicines designed with different characteristics. The influence of nanoparticle characteristics (size, zeta potential, molecular architecture surface design) was explored on biological responses evaluating their retention and absorption by rat jejunum using the Ussing chamber experimental model.

Role of the interactions of soft hyaluronan nanomaterials with CD44 and supported bilayer membranes in the cellular uptake.

Increasing valence by acting on nanomaterial morphology can enhance the ability of a ligand to specifically bind to targeted cells. Herein, we investigated cell internalization of soft hyaluronic acid (HA) nanoplatelets (NPs) that exhibit a typical hexagonal shape, flat surfaces and high aspect ratio (Γ≈12 to 20), as characterized by atomic force microscopy in hydrated conditions. Fluorescence imaging revealed that internalization of HA-NPs by a T24 tumor cell line and by macrophages was higher than native polysaccharide in a dose-dependent and time-dependent manners.

Characterization and in vitro evaluation of a vaginal gel containing Lactobacillus crispatus for the prevention of gonorrhea.

The increasing resistance of Neisseria gonorrhoeae to any current antibiotic treatment and the difficulties associated with the use of prevention means such as condom urge the need for alternative methods to prevent this sexually transmitted infection. In this work, a prevention strategy based on the use of a vaginal gel containing Lactobacilli was assessed in vitro. A Lactobacillus crispatus strain (ATCC 33197) was selected based on the published data on its ability to inhibit Neisseria gonorrhoeae.

Hierarchically built hyaluronan nano-platelets have symmetrical hexagonal shape, flattened surfaces and controlled size.

Most of nanomaterials composed of hyaluronic acid (HA) used for drug targeting are spherical. In this investigation, we suggest that the morphology of HA nanomaterials could be considered as a new parameter to control their interactions with cells. However, designing nanomaterials with elongated morphology and controlled size is still challenging.

Intestinal permeability enhancement of benzopyran HP1-loaded nanoemulsions.

The benzopyran HP1, a compound isolated from Hypericum polyanthemum, has demonstrated significant opioid-mediated antinociceptive activity after its oral administration. Despite the pharmacological potential, the poor aqueous solubility limits the oral absorption of this compound. For this reason, HP1 has been alternatively incorporated in lipid-based drug delivery systems.

Hierarchical supramolecular platelets from hydrophobically-modified polysaccharides and α-cyclodextrin: Effect of hydrophobization and α-cyclodextrin concentration on platelet formation.

Micro- and nano-platelets are a group of particles with typical flat surfaces and hexagonal shape. They are obtained by hierarchical self-assembly in water of α-cyclodextrin and polysaccharides hydrophobically-modified with alkyl chains. It is expected that the formation of well structured and cohesive platelets is driven by the interaction between alkyl chains grafted on polysaccharides and α-cyclodextrin.

New insights on the structure of hexagonally faceted platelets from hydrophobically modified chitosan and α-cyclodextrin.

A new class of non-spherical particles was recently designed in our research group by mixing a polysaccharide grafted with fatty acids and α-cyclodextrin in water. Because their flat surfaces, and according to their size, particles are called micro- or nano-platelets. Here, we varied the composition of fatty acids grafted on chitosan (oleic acid, palmitic acid or stearic acid) and characterized platelet morphology.

Intestinal permeability determinants of norfloxacin in Ussing chamber model.

Recently, many efforts are taken to identify the intestinal uptake and efflux transporters since they are responsible for the absorption of many drugs as their interactions. Norfloxacin (NFX) is a fluoroquinolone that presents low solubility and low permeability, and as a consequence, low bioavailability. In this context, the aim of this study is evaluate for the first time the intestinal permeability mechanisms of NFX by Ussing chamber model.

Cyclodextrin based nanosponge of norfloxacin: Intestinal permeation enhancement and improved antibacterial activity.

Nanosponges are a novel class of hyperbranched cyclodextrin-based nanostructures that exhibits remarkable potential as a drug host system for the improvement in biopharmaceutical properties. This work aims the development of cyclodextrin-based nanosponge of norfloxacin to improve its physicochemical characteristics. β-cyclodextrin was used as base and diphenyl carbonate as crosslinker agent at different proportions to produce nanosponges that were evaluated by in vitro and in vivo techniques.

Phase solubility studies and anti-Trichomonas vaginalis activity evaluations of metronidazole and methylated β-cyclodextrin complexes: Comparison of CRYSMEB and RAMEB.

Metronidazole (MTZ) is a 5-nitroimidazole drug used for the treatment of Trichomonas vaginalis parasitic infection. Aqueous formulations containing MTZ are restricted because apparent solubility in water of this drug is low. In this context, two methylated-β-cyclodextrins (CRYSMEB and RAMEB) were used as a tool to increase apparent solubility of MTZ in water.

Chitosan-Acrylic Polymeric Nanoparticles with Dynamic Covalent Bonds. Synthesis and Stimuli Behavior.

Drug delivery represents one of the most important research fields within the pharmaceutical industry. Different strategies are reported every day in a dynamic search for carriers with the ability to transport drugs across the body, avoiding or decreasing toxic issues and improving therapeutic activity. One of the most interesting strategies currently under research is the development of drug delivery systems sensitive to different stimuli, due to the high potential attributed to the selective delivery of the payload.

Mucoadhesive properties of low molecular weight chitosan- or glycol chitosan- and corresponding thiomer-coated poly(isobutylcyanoacrylate) core-shell nanoparticles.

The aim of the present work was to evaluate the mucoadhesive properties of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles (NPs) coated with Low Molecular Weight (LMW) chitosan (CS)- and glycol chitosan (GCS)-based thiomers as well as with the corresponding LMW unmodified polysaccharides. For this purpose, all the CS- and GCS-based thiomers were prepared under simple and mild conditions starting from the LMW unmodified polymers CS and GCS. The resulting NPs were of spherical shape with diameters ranging from 400 to 600nm and 187 to 309nm, for CS- and GCS-based NPs, respectively.

Increased intestinal permeation and modulation of presystemic metabolism of resveratrol formulated into self-emulsifying drug delivery systems.

Despite various beneficial biological properties, resveratrol lacks therapeutic applications because of poor bioavailability due to variable absorption and extensive metabolism. The present study aims at evaluating the capability of self-emulsifying drug delivery systems (SEDDS) to enhance resveratrol permeation across rat intestine and to modulate its presystemic metabolism. For that purpose, semi-solid (SS) and liquid (L) SEDDS were prepared and dispersed in an aqueous buffer to produce nanoemulsions (NE).

Supramolecular Chitosan Micro-Platelets Synergistically Enhance Anti-Candida albicans Activity of Amphotericin B Using an Immunocompetent Murine Model.

Purpose: The aim of this work is to design new chitosan conjugates able to self-organize in aqueous solution in the form of micrometer-size platelets. When mixed with amphotericin B deoxycholate (AmB-DOC), micro-platelets act as a drug booster allowing further improvement in AmB-DOC anti-Candida albicans activity.

Methods: Micro-platelets were obtained by mixing oleoyl chitosan and α-cyclodextrin in water.

M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures.

Microbicides are considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analyzed the antiviral activity of the miniCD4 M48U1 peptide formulated in hydroxyethylcellulose (HEC) hydrogel in activated peripheral blood mononuclear cells (PBMCs) infected with R5- and X4-tropic HIV-1 strains. The results demonstrate that M48U1 prevented infection by several HIV-1 strains including laboratory strains, and HIV-1 subtype B and C strains isolated from the activated PBMCs of patients.

In situ forming pluronic® F127/chitosan hydrogel limits metronidazole transmucosal absorption.

The objective of this work is to design topically-applied thermosensitive and mucoadhesive hydrogel containing metronidazole (MTZ) for the treatment of Trichomonas vaginalis infections. Hydrogel composed of pluronic® F127 (20wt%), chitosan (1wt%) and metronidazole MTZ (0.7wt%) mixture showed its ability to decrease by a factor 4 MTZ flux and apparent permeability absorption through vaginal mucosa.

Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration.

The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study.

Gelation and micellization behaviors of pluronic(®) F127 hydrogel containing poly(isobutylcyanoacrylate) nanoparticles specifically designed for mucosal application.

The aim of this investigation is to combine the advantages of pluronic(®) F127 hydrogels and nanoparticles composed of poly(isobutylcyanoacrylate) (PIBCA) core coated with a mixture of chitosan and thiolated chitosan to design novel multifunctional formulation for mucosal application. Nanoparticles offer the advantage of being mucoadhesive while pluronic(®) F127 hydrogel allowed prolonged contact time onto mucosal surfaces. This work highlights an unprecedented comprehensive study on the effect of nanoparticles on gelation and micellization behaviors of pluronic(®) F127 using rheology and micro-calorimetry experiments.

Ex vivo permeation of tamoxifen and its 4-OH metabolite through rat intestine from lecithin/chitosan nanoparticles.

Tamoxifen citrate is an anticancer drug slightly soluble in water. Administered orally, it shows great intra- and inter-patient variations in bioavailability. We developed a nanoformulation based on phospholipid and chitosan able to efficiently load tamoxifen and showing an enzyme triggered release.