Francois Chouinard

Enzymatic degradation of cross-linked high amylose starch tablets and its effect on in vitro release of sodium diclofenac.

The influence of several physicochemical parameters on enzymatic hydrolysis and the in vitro release of sodium diclofenac (SDic) from cross-linked high amylose starch (Contramid) (CLA) tablets was evaluated. These parameters included pH, ionic strength of the medium, enzyme concentration, compression force and incorporation of gel-forming polymers such as hydroxypropyl methylcellulose (HPMC), poly(ethylene oxide) (PEO) and poly(vinyl alcohol) into the tablet. Pure CLA tablets were incubated in phosphate buffer (pH 6.8) containing alpha-amylase and the extent of enzymatic erosion was determined by gravimetry. Release of SDic from CLA tablets, in the presence of alpha-amylase, was measured using a USP type III dissolution apparatus. For low alpha-amylase concentrations (<2250 IU/l), the drug release was mainly diffusion-controlled. At higher alpha-amylase concentrations (>4500 IU/l) both diffusion and erosion contributed to the release of SDic. The hydrolysis kinetics of CLA tablets by alpha-amylase was biphasic. During the first phase (2-4 h), the hydrolysis rate was hyperbolically related to the alpha-amylase concentration but was practically alpha-amylase concentration-independent during the second phase. Enzymatic erosion and drug release kinetics appear to be relatively independent of ionic strength, pre-incubation time in simulated gastric fluid, and compression force of the tablets (6-34 kN). Incorporation of HPMC or PEO into the tablet resulted in a significant decrease of both tablet erosion and drug release rates.

Preparation and purification of polyisohexylcyanoacrylate nanocapsules

Abstract Nanocapsules (200 nm diameter) were prepared by interfacial polymerization of isohexylcyanoacrylate in an oil-in-water emulsion. Sulphur dioxide was added to the monomer prior to its dissolution in the oil-ethanol phase in order to avoid immediate polymerization. Upon addition to the aqueous phase, interfacial polymerization occurred resulting in the formation of nanocapsules. The effect of different variables on nanocapsule size was evaluated. Miglyol concentration played a major role by controlling the size of emulsified droplets while SO 2 and pH only slightly affected nanocapsule size. Monomer concentration showed a significant effect on the density, indicating that polymeric walls of different thicknesses can be obtained. Finally, a purification method based on centrifugation and redispersion was developed.

Biodegradable Nanospheres Containing Phthalocyanines and Naphthalocyanines for Targeted Photodynamic Tumor Therapy

Preparation methods of cyanoacrylic nanocapsules or nanoparticles containing phthalocyanines and naphthalocyanines are described. Nanocapsules were obtained by interfacial polymerization in an oil-in-water emulsion. Drug encapsulation efficiency depended upon drug concentration, ethanol concentration, and phthalocyanine sulfonation degree and reached 100% in some cases. Nanocapsules size ranged from 150 to 250 nm and varied with phthalocyanine sulfonation degree and pH of the aqueous phase. Nanoparticles were prepared by the addition of monomer to an aqueous phase containing hydrophilic phthalocyanine derivatives. Depending upon the pH, sizes ranged from 10 to 380 nm. Drug binding was between 75 and 80%. These new preparations could prove useful in the photodynamic treatment of tumors.

Effect of various poloxamer coatings on in vitro adhesion of isohexylcyanoacrylate nanospheres to rat ileal segments under liquid flow

This work evaluates the bioadhesive properties of isohexylcyanoacrylate nanocapsules coated with poloxamers 407, 238, 403 and poloxamine 908 compared to nanoparticles coated with poloxamer 407. Nanocapsules (oil droplets surrounded by a polymeric wall) and nanoparticles (plain polymeric spheres) were prepared, labelled with covalently linked with tetraiodinated 125I-phthalocyanine-Zn and laid on the rat ileal segment in vitro. After 0 and 10 min following transfer of nanospheres, a liquid flow was started. In all cases studied, a fraction of the nanospheres was not adherent when perfusion was initiated and was recovered in the first fraction. The other fraction, representing approx. 45% of the nanospheres, adhered firmly and was removed very slowly by the liquid flow. In addition, when nanocapsules were coated with poloxamers 238 and 407, the percentage adhesion increased between and 10 min. Our results demonstrate that the greatest extent of mucoadhesion was achieved with poloxamers possessing a short centra polyoxypropylene (POP) chain and long polyoxyethylene (POE) side chains. The results are discussed on the basis of diffusion of the POE groups into the mucin network and creation of secondary chemical adhesive bonds (Van der Waals type) between the nanosphere coating and mucus.

Poly(alkylcyanoacrylate) nanocapsules: physicochemical characterization and mechanism of formation.

Nanocapsules of poly(isobutylcyanoacrylate) and poly(isohexylcyanoacrylate) were prepared by addition of the monomer to an organic phase and subsequent mixing of the organic phase to an aqueous phase containing poloxamer 188, 238 or 407. Gel permeation chromatography indicated that in contrast to literature reports, polymerization occurred in the organic phase and nanocapsules were obtained by interfacial precipitation of the polymer without any significant change of the molecular weight. Addition of SO2 to the organic phase before the introduction of the monomer allowed preparation of nanocapsules with a lower molecular weight. Nanospheres were prepared in a similar way albeit using an organic phase that was completely miscible within the aqueous phase so that solid spheres were obtained. Density gradient centrifugation revealed that nanocapsules had a density intermediate between nanospheres and an emulsion prepared in the same way without addition of monomer to the organic phase. Further, the process used to prepare nanocapsules had a high yield since no oil droplets or nanospheres were obtained by this process. Zeta potential of the nanocapsules and spheres was found to be related to the molecular weight of the polymer: values as high as ≈ −42 mV were obtained for low molecular weight nanocapsules (MW ≈ 1000) compared to ≈ −l0mV for the emulsion and the high molecular weight nanocapsules (MW ≈ 100 000). Surface charge of the nanocapsules and molecular weight of their polymeric wall conditioned the adsorption capacity of poloxamers. Moreover, the highest adsorption was measured with the most hydrophobic poloxamer. These observations agree with previous work conducted on hydrophobic surfaces.

Association of cyclosporin to isohexylcyanoacrylate nanospheres and subsequent release in human plasma in vitro

Polyisohexylcyanoacrylate nanocapsules containing cyclosporin were prepared by mixing in a 1:2 ratio an oil/ethanol solution of monomer and drug with an aqueous phase. Drug nanoencapsulation rate was controlled by its partition coefficient between the inner (organic) and outer (aqueous) phases. Thus highest encapsulation yields (88 per cent) were achieved by reducing cyclosporin solubility in the aqueous phase, i.e. by reducing ethanol concentration under reduced pressure, achieving a 3-fold volume reduction. Due to the relative insolubility of cyclosporin in water, no drug was released from the nanocapsules during storage in this injectable vehicle. Upon a 1/5 dilution in human plasma at 37 degrees C in vitro around 40 per cent of the initially encapsulated cyclosporin diffused quickly out of the capsules and an equilibrium was reached, the drug being most likely dissolved in the fatty compartment of the plasma such as lipoproteins, etc. This release mechanism is different from plain polymeric nanoparticles. Indeed, in this case the drug was released in two phases: an initial burst (around 60 per cent) of adsorbed drug as a result of the dilution, followed by a slow release (around 20 per cent over 3 h) which is likely to result from the progressive enzymatic erosion of the polymer. The initial burst was markedly more pronounced (around 80 per cent) when nanoparticle suspensions were evaporated to 1/3 of their initial volume under reduced pressure. Finally, experiments performed at 0 degree C allowed a reduction of the fraction released immediately from both types of nanospheres, probably because of a reduced solubility in plasma. In the case of nanoparticles the second phase of slow release is also inhibited at 0 degree C, in agreement with an enzymatically controlled release mechanism.