Topological defects in polycrystalline hexosomes from β-cyclodextrin fatty esters.

Colloidal nanoparticles were prepared by aqueous self-assembly of amphiphilic β-cyclodextrins (βCDs) acylated on their secondary face with C chains to a total degree of substitution of 7.0, a thermolysin-catalyzed transesterification process. The small-angle X-ray scattering pattern of the nanoparticles was consistent with a reverse hexagonal organization.

Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery.

We previously developed two optimized formulations of dexamethasone acetate (DXMa) hydrogels by means of special cubic mixture designs for topical ocular administration. These gels were elaborated with hydroxypropyl-β-CD (HPβCD) and hydroxypropyl-γ-CD (HPγCD) and commercial hydrogels in order to enhance DXMa water solubility and finally DXMa's ocular bioavailability and transcorneal penetration. The main objective of this study was to characterize them and to evaluate , , and their safety, biopermanence, and transcorneal permeation.

Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation.

Ocular inflammation is one of the most common symptom of eye disorders and diseases. The therapeutic management of this inflammation must be rapid and effective in order to avoid deleterious effects for the eye and the vision. Steroidal (SAID) and non-steroidal (NSAID) anti-inflammatory drugs and immunosuppressive agents have been shown to be effective in treating inflammation of the ocular surface of the eye by topical administration.

Pharmacokinetic study of intravenously administered artemisinin-loaded surface-decorated amphiphilic γ-cyclodextrin nanoparticles.

Artemisinin and its derivatives are currently recommended by World Health Organization for the treatment of malaria. Severe malaria requires a parenteral administration of artemisinin-based formulations. However, the effective use of artemisinin is limited by the pharmacokinetic characteristics of the drug (low water solubility, poor bioavailability and short half-life).

Capillary electrophoretic apparatus for the endpoint detection in microtitration methods.

Titration methods are routinely used in the laboratories for the quantification of acids and bases, for the complexometric determination of metal ions and for the ion-pair titrations of drugs in pharmaceutical control. They also find application in a wide variety of chemical and biochemical studies. However, conventional titration methods (CTM) require large amounts of samples that are not always available.

Investigation of Combined Cyclodextrin and Hydrogel Formulation for Ocular Delivery of Dexamethasone Acetate by Means of Experimental Designs.

Dexamethasone acetate (DXMa) has proven its efficiency to treat corneal inflammation, without a great propensity to increase intraocular pressure. Unfortunately, its poor aqueous solubility, associated with a rapid precorneal elimination, results in a low drug bioavailability and a low penetration after topical ocular administration. The main objective of this study was to improve the apparent aqueous solubility of DXMa using cyclodextrins.

Inline Coupling of Electrokinetic Preconcentration Method to Taylor Dispersion Analysis for Size-Based Characterization of Low-UV-Absorbing Nanoparticles.

The inline coupling of the field-amplified sample injection (FASI) to Taylor dispersion analysis (TDA) was used to characterize low-UV absorbing carboxylated silica nanoparticles (cNPs). The hydrodynamic diameters (D) were measured by using a commercial capillary electrophoresis instrument. The proposed methodology did not require any complicated instruments or chromophoric dye to increase the detection sensitivity.

New nanoparticles obtained by co-assembly of amphiphilic cyclodextrins and nonlamellar single-chain lipids: Preparation and characterization.

This work aimed at preparing new nanoscale assemblies based on an amphiphilic bio-esterified β-cyclodextrin (β-CD), substituted at the secondary face with n-decanoic fatty acid chains (β-CD-C), and monoolein (MO) as new carriers for parenteral drug delivery. Stable binary (β-CD-C/MO) and ternary (β-CD-C/MO/stabilizer) nanoscale assemblies close to 100nm in size were successfully prepared in water by the solvent displacement method. The generated nanoparticles were fully characterized by dynamic light scattering, transmission electron microscopy, small-angle X-ray scattering, residual solvent analysis, complement activation and the contribution of each formulation parameter was determined by principal component analysis.

Self-Assembly of Amphiphilic Biotransesterified β-Cyclodextrins: Supramolecular Structure of Nanoparticles and Surface Properties.

A series of β-cyclodextrin (βCD) amphiphilic derivatives with varying degrees of substitution were prepared by acylating βCDs on their secondary face using thermolysin to catalyze the transesterification. After dissolution in acetone, the βCD-C derivatives (n = 8, 10, 12, 14) were nanoprecipitated in water, where they self-organized into structured particles that were characterized using cryo-transmission electron microscopy (cryo-TEM) images and small-angle X-ray scattering (SAXS) data. Two types of morphologies and ultrastructures were observed depending on the total degree of substitution (TDS) of the parent derivative.

Mesoporous self-assembled nanoparticles of biotransesterified cyclodextrins and nonlamellar lipids as carriers of water-insoluble substances.

Soft mesoporous hierarchically structured particles were created by the self-assembly of an amphiphilic deep cavitand cyclodextrin βCD-nC (degree of substitution n = 7.3), with a nanocavity grafted by multiple alkyl (C) chains on the secondary face of the βCD macrocycle through enzymatic biotransesterification, and the nonlamellar lipid monoolein (MO). The effect of the non-ionic dispersing agent polysorbate 80 (P80) on the liquid crystalline organization of the nanocarriers and their stability was studied in the context of vesicle-to-cubosome transition.

Biocompatible Double-Membrane Hydrogels from Cationic Cellulose Nanocrystals and Anionic Alginate as Complexing Drugs Codelivery.

A biocompatible hydrogel with a double-membrane structure is developed from cationic cellulose nanocrystals (CNC) and anionic alginate. The architecture of the double-membrane hydrogel involves an external membrane composed of neat alginate, and an internal composite hydrogel consolidates by electrostatic interactions between cationic CNC and anionic alginate. The thickness of the outer layer can be regulated by the adsorption duration of neat alginate, and the shape of the inner layer can directly determine the morphology and dimensions of the double-membrane hydrogel (microsphere, capsule, and filmlike shapes).

Self-assembled biotransesterified cyclodextrins as potential Artemisinin nanocarriers. II: In vitro behavior toward the immune system and in vivo biodistribution assessment of unloaded nanoparticles.

In a previous study, we reported on the formulation of Artemisinin-loaded surface-decorated nanoparticles (nanospheres and nanoreservoirs) by co-nanoprecipitation of PEG derivatives (PEG1500 and PEG4000-stearate, polysorbate 80) and biosynthesized γ-CD fatty esters. In the present study, the co-nanoprecipitation was extended to the use of a PEGylated phospholipid, namely DMPE-PEG2000. As our goal was to prepare long-circulating nanocarriers for further systemic delivery of Artemisinin (ART), here, we have investigated, on the one hand, the in vitro behavior of these surface-modified γ-CD-C10 particles toward the immune system (complement activation and macrophage uptake assays) and, on the other hand, their biodistribution features in mice.

Progress in developing amphiphilic cyclodextrin-based nanodevices for drug delivery.

Nowadays, colloidal drug carriers represent an alternative to solve drug bioavailabily problems. During the past two decades, colloidal drug carriers have proved to improve the therapeutic index of drugs and thus increase their efficacy and/or reduce their toxicity. However, the major challenge in the development of these drug carriers remains the search for materials able to self-organize into stable nanoscale systems.

Quantitative evaluation of the combination between cytotoxic drug and efflux transporter inhibitors based on a tumour growth inhibition model.

ATP-Binding Cassette transporters such as ABCG2 confer resistance to various anticancer drugs including irinotecan and its active metabolite, SN38. Early quantitative evaluation of efflux transporter inhibitors-cytotoxic combination requires quantitative drug-disease models. A proof-of-concept study has been carried out for studying the effect of a new ABCG2 transporter inhibitor, MBLI87 combined to irinotecan in mice xenografted with cells overexpressing ABCG2.

A template model for studying anticancer drug efflux transporter inhibitors in vitro.

Efflux transporters play an important role in drug absorption and also in multidrug resistance. ABCG2 (BCRP) is an efflux transporter conferring cross-resistance to mitoxantrone (Mit), irinotecan (CPT11), and its active metabolite SN38. MBLI87, a new ABCG2 inhibitor has proven its efficacy against ABCG2-mediated efflux in vitro and in vivo.

Monodisperse nanoparticles from self-assembling amphiphilic cyclodextrins: modulable tools for the encapsulation and controlled release of pharmaceuticals.

Selective chemical functionalization of cyclodextrins (CDs) is a readily amenable methodology to produce amphiphilic macromolecules endowed with modulable self-organizing capabilities. Herein, the synthesis of well-defined amphiphilic CD derivatives, with a "skirt-type" architecture, that incorporate long-chain fatty esters at the secondary hydroxyl rim and a variety of chemical functionalities (e. g.

Self-assembled biotransesterified cyclodextrins as Artemisinin nanocarriers - I: formulation, lyoavailability and in vitro antimalarial activity assessment.

We recently reported a one-step transesterification of cyclodextrins (CDs) by vinyl-acyl fatty esters catalyzed by thermolysin. By using the solvent displacement method and depending on the experimental conditions, the CD derivatives grafted with decanoic alkyl chains (CD-C(10)) yielded either nanosphere or nanoreservoir-type systems with a size ranging from 70 to 220 nm. Both types of nanostructures were able to associate artemisinin (ART), a well-known antimalarial lipophilic drug.

Physicochemical characterization of α-, β-, and γ-cyclodextrins bioesterified with decanoate chains used as building blocks of colloidal nanoparticles.

Nanoparticles of amphiphilic α-, β-, and γ-cyclodextrins were obtained by formulation of cyclodextrins enzymatically transesterified with vinyl decanoate. The product of this synthesis is a mixture of bioesterified cyclodextrins with various degrees of substitution (DS) presenting for a same DS different regio-isomers. In a first step, the efficiency of a MALDI-TOF procedure to characterize the average molecular weight of the derivative bulk mixture was demonstrated by comparing the results with those obtained from complementary NMR and HPLC techniques.

Antimitotic and antiproliferative activities of chalcones: forward structure-activity relationship.

A series of 59 chalcones was prepared and evaluated for the antimitotic effect against K562 leukemia cells. The most active chalcones were evaluated for their antiproliferative activity against a panel of 11 human and murine cell cancer lines. We found that three chalcones were of great interest as potential antimitotic drugs.

Nanoparticles of beta-cyclodextrin esters obtained by self-assembling of biotransesterified beta-cyclodextrins.

The synthesis of decanoate beta-cyclodextrin esters (beta-CDd) and hexanoate beta-cyclodextrin esters (beta-CDh) was biocatalyzed by thermolysin from native beta-cyclodextrin (beta-CD) and vinyl hexanoate or vinyl decanoate used as acyl donors. The products were chemically characterized by infrared, NMR, and mass spectrometry. Both beta-CDd and beta-CDh esters were identified as a mixture of beta-CD preferentially substituted on the C2 position by the corresponding acyl chain.

Efficient size control of amphiphilic cyclodextrin nanoparticles through a statistical mixture design methodology.

Purpose: the aim of the study was to investigate size control of amphiphilic beta-cyclodextrin nanoparticles obtained by solvent displacement technique.

Methods: An experimental design methodology for mixture design was undertaken using D-optimal approach with the following technique variables: water fraction X1 (40-70% v/v), acetone fraction X2 (0-60% v/v) and ethanol fraction X3 (0-60% v/v).

Results: The resulting quadratic model obtained after logarithmic transformation of data and partial least-square regression was statistically validated and experimentally checked.

Conformational states and thermodynamics of alpha-lactalbumin bound to membranes: a case study of the effects of pH, calcium, lipid membrane curvature and charge.

The study of the conformational changes of bovine alpha-lactalbumin, switching from soluble states to membrane-bound states, deepens our knowledge of the behaviour of amphitropic proteins. The binding and the membrane-bound conformations of alpha-lactalbumin are highly sensitive to environmental factors, like calcium and proton concentrations, curvature and charge of the lipid membrane. The interactions between the protein and the membrane result from a combination of hydrophobic and electrostatic interactions and the respective weights of these interactions depend on the physicochemical conditions.

Influence of chemical structure of amphiphilic beta-cyclodextrins on their ability to form stable nanoparticles.

The aim of the study was to establish a correlation between the chemical structure of amphiphilic beta-cyclodextrins (beta-CDa) and their ability to form stable nanospheres. Amphiphilic derivatives were obtained according to an optimized well-known three-step synthesis. The selective acylation of the secondary face of beta-CD being well controlled, several beta-CDa presenting different substitution degree were synthesized.

Chromatographic determination of the association constants between nimesulide and native and modified beta-cyclodextrins.

The retention of a non-steroidal anti-inflammatory drug (NSAID), i.e. nimesulide, in high performance liquid chromatography (HPLC) was investigated using a phenyl bond silica column and beta-cyclodextrin (beta-CD) or hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as mobile phase additive (0-10 mM).