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.

Crystal and molecular structure of V-amylose complexed with ibuprofen.

Rectangular V-amylose single crystals were prepared by adding racemic ibuprofen to hot dilute aqueous solutions of native and enzymatically-synthesized amylose. The lamellar thickness increased with increasing degree of polymerization of amylose and reached a plateau at about 7 nm, consistent with a chain-folding mechanism. The CP/MAS NMR spectrum as well as base-plane electron and powder X-ray diffraction patterns recorded from hydrated specimens were similar to those of V-amylose complexed with propan-2-ol.

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).

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.

Polymorphism of crystalline complexes of V-amylose with fatty acids.

The crystallization of amylose from dilute solutions in the presence of a series of linear saturated fatty acids (C3 to C20) was investigated by varying the fatty acid concentration, crystallization temperature and solvent composition (DMSO:water in various ratios). The morphology and structure of the resulting model lamellar crystals were characterized by transmission electron microscopy as well as electron and X-ray diffraction. By adequately controlling the crystallization parameters, all fatty acids could induce the formation of both 6- and 7-fold V-amylose single helices, indicating that the amylose conformation was independent of the chain length of the complexing molecule.

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).

State of knowledge of Cameroonian drug prescribers on pharmacovigilance.

Introduction: The present study conducted in Cameroon from June 2013 to February 2014 aimed to estimating the level of pharmacovigilance knowledge and practice of health professionals in Cameroon.

Methods: We conducted a descriptive cross-sectional survey on 149 health professionals in Cameroon from June to September 2013. Data were analyzed using software IBM SPSS 20.

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.

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.

Characterisation of complex amphiphilic cyclodextrin mixtures by high-performance liquid chromatography and mass spectrometry.

It is established that amphiphilic beta-cyclodextrins chemically modified with alkyl chains on the secondary face exhibit self-organisation properties yielding stable nanospheres or nanoparticles. The ability of these promising colloidal drug carriers to encapsulate drugs being partly related to the internal structure of nanosystems, precise characterisation methods are required to control their synthesis procedure. The present work describes the development of complementary analytical methods based on reversed-phase high-performance liquid chromatography (RPLC) coupled to evaporative light-scattering detection (ELSD) and electrospray ionisation-mass spectrometry (ESI-MS) to characterize various beta-cyclodextrins enzymatically transesterified by vinyl-acyl fatty esters (the number of carbon atom in the acyl chain varying from 4 to 12).

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.

Differential effects of cyclodextrins and derivatives on the biological behavior of the myocardial perfusion imaging agent 99mTcN-NOET.

In addition to improving drug solubilization, cyclodextrins (CDs) also affect the biological behavior of the included compound. We evaluated the effects of two natural CDs beta-CD and gamma-CD, and six beta-CD derivatives, Dimeb, Trimeb, SBb, 2-HP, 6AD, and 6 MTU on the biological behavior of (99m)TcN-NOET, a technetium-99m-labeled, lipophilic compound readily detectable through radioactivity assessment. Determination of CDs' affinities for (99m)TcN-NOET indicated that the cavity size of gamma-CD was not suitable for (99m)TcN-NOET inclusion, and that beta-CD derivatization mostly resulted in decreased CDs affinities for (99m)TcN-NOET to various extents compared with the natural beta-CD.

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).