Francisco Otero-Espinar | PubMed Health

PubMed2006

Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capability.

The influence of the proportion of acrylamidomethyl-gamma-cyclodextrin (gamma-CD-NMA) on loading and release of the hydrophobic triamcinolone acetonide (TA) and the hydrophilic propranolol (PR) by acrylic acid hydrogels was evaluated. gamma-CD-NMA was synthesized by condensation of gamma-cyclodextrin (gamma-CD) with N-(hydroxymethyl) acrylamide. Hydrogels were prepared with gamma-CD-NMA and sodium acrylate (3 M or 4 M), using N,N'-methylen(bisacrylamide) (BIS) as cross-linker, by free radical polymerization into glass moulds of 2 mm wide and were cut as discs (10 mm diameter). gamma-CD-NMA did not modify the pH-dependent swelling of the hydrogels, but significantly increased the swelling degree in the 40:60 ethanol:water, medium in which TA can be dissolved. Hydrogels prepared with gamma-CD-NMA above 5% (w/w of total monomers) showed a remarkably higher capacity to load TA, e.g., 33 mg/g dry hydrogel versus 0.6 mg/g dry hydrogel without gamma-CD-NMA. This is explained by the formation of 1:1 inclusion complexes of TA with gamma-CD mers that overcomes the lack of interactions with the acrylic groups of the network. The release of TA in water, 0.1 N HCl, or pH 6.8 phosphate buffer was sustained for at least 24 h, whatever the pH and the composition of the medium used. In contrast, loading of PR from the water solutions was greater for hydrogels prepared with 3 M acrylate than with 4 M acrylate, irrespective to their content in gamma-CD-NMA, and in less than 2 h ca. 80% PR was released. The lower affinity of PR for the gamma-CD cavities, compared to the strong intensity of the electrostatic interactions with the acrylic acid groups, explains why the incorporation of gamma-CD-NMA did not increased the loading and control release capacity of the hydrogels of this hydrophilic drug. In summary, the copolymerisation of CD with acrylic monomers can provide highly hydrophilic pH-sensitive networks which load large amounts of hydrophobic drugs and release them in a sustained way.

Calorimetry, Differential Scanning↗

PubMed2004

Efficacy of alpha-cyclodextrin against experimental cryptosporidiosis in neonatal goats.

The efficacy of orally administered tablets containing alpha-cyclodextrin, an excipient used in the pharmaceutical industry with demonstrated anticryptosporidial activity in vitro and in neonatal mice, was evaluated in neonatal goat kids. The formulation was evaluated for hardness and was subjected to in vitro drug release studies. Twenty goat kids were orally inoculated with 10(6) oocysts of C. parvum within the first 6 days of age. Half of the animals were treated by oral administration of four tablets of alpha-cyclodextrin/day (500 mg/kg of body weight) for six consecutive days, the treatment beginning on the day of inoculation. Infection was monitored by daily examination of faecal samples from the first day to 25 days post-inoculation. The criteria studied in evaluating efficacy were: oocyst shedding, presence of diarrhoea and weight gain at 15 and 25 days post-inoculation. alpha-cyclodextrin was effective when given at the beginning of infection: there was a longer pre-patent period, a reduction in the patent period and a decrease in the intensity of infection, these differences being statistically significant (P < 0.05) compared with untreated neonatal kids. Moreover, except in one animal, the diarrhoea was prevented in infected neonatal kids. Animals from both groups increased the body weight and no significant differences were seen between the two groups.

Animals↗