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. Its probiotic properties were first characterized. Then, a thermo-sensitive hydrogel containing 21.5% of poloxamer 407, 1% of sodium alginate and 9log10 CFU of Lactobacillus crispatus per gel sample (5 g) was developed. The gelation temperature and the rheological characteristics of this formulation appeared suitable for a vaginal administration. Lactobacillus crispatus was viable in the gel for six months although a large amount of the bacteria was not culturable. The ability of Lactobacillus crispatus to inhibit Neisseria gonorrhoeae was still observed with the gel. Such system, thus, appeared promising for the prevention of gonorrhea.

Rheological and syringeability properties of highly concentrated human polyclonal immunoglobulin solutions.

This study of highly concentrated polyvalent immunoglobulin solutions, IgG, aimed at analyzing the relationships between protein concentration and aggregation on the one hand and viscosity on the other hand. Viscosity variations as a function of IgG concentration showed two well-defined behaviours: a Newtonian behaviour for low-concentrated solutions and a shear-thinning behaviour for highly concentrated ones. The viscosity data fitted very well with the Mooney model, suggesting the absence of intermolecular interactions in the IgG solutions that behaved like a non-interacting suspension of hard particles. The polyclonal nature of IgG seems to prevent intermolecular interaction. The shape factor, determined from Mooney fitting, revealed a non-spherical shape of the polyclonal IgG molecules. The rheological properties were also correlated with the injection force (F) through hypodermic needles by syringeability tests. Here, F was mainly affected by three parameters: the solution viscosity, the injection flow rate, and the needle characteristics. In fact, syringeability tests showed that F increased with IgG concentration and flow rate and decreased with the internal diameter of the needle. A zone for optimal injection conditions was then identified taking into account the different affecting parameters and mainly a maximum force for manual injection, which was fixed at 30N.

Structural and rheological properties of chitosan semi-interpenetrated networks.

The local structure and the viscoelastic properties of semi-interpenetrated biopolymer networks based on cross-linked chitosan and poly(ethylene oxide) (PEO) were investigated by Small Angle Neutron Scattering and rheological measurements. The specific viscosity and the entanglement concentration of chitosan were first determined, respectively, by capillary viscosimetry and steady-state shear rheology experiments performed at different polymer concentrations. Mechanical spectroscopy was then used to study the gelation process of chitosan/PEO semi-interpenetrated networks. By fitting the frequency dependence of the elastic and loss moduli with extended relations of relaxation shear modulus around the sol-gel transition, it was shown that the addition of PEO chains had a significant effect on the viscoelastic properties of aqueous chitosan networks but no effect on the gelation time. The improvement of mechanical properties was in accordance with the correlation length decrease deduced from Small Angle Neutron Scattering experiments.

In vitro and in vivo characteristics of a thermogelling and bioadhesive delivery system intended for rectal administration of quinine in children.

The aim of this work was to improve the rectal bioavailability of quinine hydrochloride by designing thermosensitive and mucoadhesive gels intended for rectal delivery. The rheological and mucoadhesive properties of poloxamer 407 solutions have been modulated by addition of hydroxypropylmethycellulose (HPMC) and propanediol-1,2. In vitro release and rectal absorption of quinine have been highlighted by a dialysis dissolution testing method and by the determination of bioavailability of the different formulations in rabbits. Increasing the proportions of HPMC and poloxamer in the formulations resulted in a prolonged release of quinine. Indeed, compared to the DT 50% of a rectal solution and a simple HPMC gel (27 and 65 min, respectively) the DT 50% of thermosensitive ternary systems was increased and ranged between 80 and 138 min, depending on the system composition. The release rate depended strongly on the elasticity of the gels after thermogelation. The absolute rectal bioavailability of quinine determined in rabbits was significantly improved with these thermosensitive and adhesive systems. It increased from 62% for the rectal solution to 98% for a ternary system 16/0.5/30 (poloxamer (16%)/HPMC (0.5%)/propanediol-1,2 (30%)). As a result of combined bioadhesion and prolonged release of quinine in vivo, higher average values of MRT and t(max) (9.1+/-0.2h and 30 min, respectively) were obtained compared to the rectal solution (6.9+/-0.9h and 15 min, respectively). Moreover, these formulations presented a very good rectal tolerance. Modulation by HPMC of the viscoelastic and mucoadhesive properties of poloxamer 407 thermogelling solutions allowed a prolonged release of quinine hydrochloride and an improvement of bioavailability in rabbit.

Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine.

The aim of this work was to formulate and characterize thermosensitive gels based on poloxamer 407, a thermosensitive polymer, and hydroxypropylmethylcellulose (HPMC), a bioadhesive polymer, intended for the rectal delivery of quinine in children. In order to avoid the macroscopic phase separation between the two polymers it was necessary to add propanediol-1,2. After the formulation of stable ternary systems, their rheological properties were studied as a function of temperature. It was thus possible to obtained the gelation temperature of the systems as well as their elastic modulus, G', at 37 degrees C. It appeared that HPMC in the presence of propanediol-1,2 had a synergistic effect on the gelation of poloxamer 407. Tests on the rabbit rectal mucous membrane, founded on a technique of traction of the adhesive/adhered joint, made it possible to characterize the bioadhesive properties of the gels by measuring the work of adhesion, W, and the maximum detachment force, F(max). Over small concentration ranges of poloxamer and HPMC, very important variations of the viscoelastic and mucoadhesives properties were observed. It was shown that the viscoelastic and the bioadhesive properties were tightly correlated. Indeed, an empirical equivalence relation was established between the shear frequency and the rate of deformation in traction and allowed to describe all our samples by a master curve. This master curve would make it possible to predict the values of W at various rates of traction by the simple non-destructive measurement of the elastic modulus, G', at an equivalent shear frequency.

Water state characterization, swelling behavior, thermal and mechanical properties of chitosan based networks.

Two kinds of chitosan-based hydrogels, a crosslinked chitosan reference gel and a chitosan-poly(ethylene oxide) semi-interpenetrating network (semi-IPN), with potential pH-sensitive swelling and drug delivery properties are characterized. Swelling studies were performed on the two kinds of hydrogels by differential scanning calorimetry (DSC) at pH 1.2 and by the gravimetric method at pH 1.2 and pH 7.2. Both methods lead to similar results. If pH-dependent swelling properties were observed with both hydrogels, they were however improved for the semi-IPN. The amount of bound water in the xerogels could be determined from DSC measurements and a thermogravimetric analysis. The results obtained by both techniques were in good agreement and indicated that the semi-IPN contained more bound water than the reference gel probably due to the presence of the hydrophilic poly(ethylene oxide) chains. Young modulus of the swollen hydrogels was determined by indentation analysis. The semi-IPN displayed improved mechanical properties compared to the reference gel.

Controlled release of vancomycin from poloxamer 407 gels.

The purpose of this study was to investigate Poloxamer 407 25% (w/w) formulations aimed at prolonging the residence time of vancomycin, a time-dependent antibiotic, in a body site with a high infectious risk. Reversible thermal gelation of the formulations permitted their local injection in liquid form and in situ gelation as they warmed to body temperature. Neither the rheological properties of the Poloxamer matrices nor the antibacterial activity of vancomycin was altered by their combination. In vitro, the dispersed form exhibited prolonged release, with a lower diffusion coefficient of vancomycin compared to the solubilized form (4.7x10(-8) vs 2. 1x10(-7) cm(2) s(-1)131 mg l(-1) for the solubilized form), followed by lower but effective antibacterial levels for at least 8 days. Controlled-release profiles, good preservation of vancomycin activity, good tolerability in rats, and ease of administration suggest that Poloxamer 407 may be useful as a vancomycin delivery vehicle for local prophylaxis of infections, especially in prosthetic surgery.