Biomedical subjects

A Santoveña

Publications and source records attributed to A Santoveña.

5 recordsLinked to original sources

PubMed2006

A mathematical model for interpreting in vitro rhGH release from laminar implants.

Recombinant human growth hormone (rhGH), used mainly for the treatment of growth hormone deficiency in children, requires daily subcutaneous injections. The use of controlled release formulations with appropriate rhGH release kinetics reduces the frequency of medication, improving patient compliance and quality of life. Biodegradable implants are a valid alternative, offering the feasibility of a regular release rate after administering a single dose, though it exists the slight disadvantage of a very minor surgical operation. Three laminar implant formulations (F(1), F(2) and F(3)) were produced by different manufacture procedures using solvent-casting techniques with the same copoly(D,L-lactic) glycolic acid (PLGA) polymer (Mw=48 kDa). A correlation in vitro between polymer matrix degradation and drug release rate from these formulations was found and a mathematical model was developed to interpret this. This model was applied to each formulation. The obtained results where explained in terms of manufacture parameters with the aim of elucidate whether drug release only occurs by diffusion or erosion, or by a combination of both mechanisms. Controlling the manufacture method and the resultant changes in polymer structure facilitates a suitable rhGH release profile for different rhGH deficiency treatments.

Biocompatible Materials↗

PubMed2005

Structural properties of biodegradable polyesters and rheological behaviour of their dispersions and films.

This paper focuses on the dependence of the rheological properties of PLA-PEG and PLGA dispersions and films on the polymer structural properties, in order to obtain useful information to predict and explain the performance of polyester films as drug-delivery systems. In this study, one PLA-PEG and three PLGA polymers of different molecular mass were synthesized and characterized by NMR, GPC, DSC and TGA-FT-IR. To characterize the viscoelastic behaviour of concentrated solutions in dichloromethane and of the films obtained by a solvent-casting technique, oscillatory shear rheometry was used. The polymer dispersions showed a characteristic Newtonian viscous behaviour, but with different consistency index depending on the nature of the polymer. Freshly prepared, PLGA and PLA-PEG films had elastic modulus (G') greater than viscous modulus (G"). The decrease in both moduli caused by an increase in temperature from 25 to 37 degrees C was especially marked for the polymers with T(g) below or around 25 degrees C (PLGA 27 kDa and PLA-PEG 27 kDa). After being immersed in pH 7.4 aqueous solution for one week, PLGA films showed a significant increase in both G' and G", due to the promotion of polymer-polymer interactions in a non-solvent medium. In contrast, the PLA-PEG film became softer and more hydrated, due to the amphiphilic character of the polymer. The water taken up by the film acted as a plasticizer and induced the softening of the system. These results suggest that the presence of PEG chains exerts a strong influence on the mechanical properties of polyesters films and, possibly, the performance as coating or matrices of drug-delivery systems.

Biodegradation, Environmental↗

PubMed2004

Rheological properties of PLGA film-based implants: correlation with polymer degradation and SPf66 antimalaric synthetic peptide release.

This paper reports on the rheological properties of poly(D,L-lactic-co-glycolic acid) polymers (PLGA) dispersions used to form films and of the implants prepared by compression of SPf66 antimalaric peptide between several films, before application and during drug release. 25% PLGA (M(w)=48,000Da) dispersions in dichloromethane showed viscous Newtonian behaviour, being easy flowing and adaptable to the moulds. Evolution of viscoelastic properties, polymer molecular weight, and SPf66 release pattern from the implants immersed in various media was evaluated. Oscillatory shear test showed that freshly prepared implants have an elastic modulus, G', greater than the viscous modulus, G", being both practically independent of angular frequency. After 6 weeks immersion in a pH 7.4 phosphate buffer, G' and G" increased in almost one order of magnitude, despite of a significant polymer degradation. Polymer molecular weight decreased slowly during the first 10 days of immersion (a similar pattern was obtained at pHs 2 and 7.4) and then the degradation process accelerated (degradation index on day 7 equals to 0.89, and on day 14 equals to 16.5). SPf66 release profile followed a pattern similar to that of the polymer degradation index. These observations are explained in terms of changes in polymer structure and conformation that happen in the implant.

Absorbable Implants↗

PubMed2004

Stability indicating method for SPf66 antimalarial peptide in solution.

Stability studies on the SPf66 antimalarial peptide with different pH and temperature conditions were carried out. The degradation mechanism was elucidated by the size-exclusion chromatography (SEC) technique and the experimental data obtained at 37 degrees C and different pH were fitted to a kinetic degradation model that could explain the loss of its immunogenic capacity. At 5, 25, 37, and 70 degrees C and pH 2, changes were detected in the areas of the different species, although the values obtained could not be fitted to any known degradation kinetics.

Chromatography, Gel↗

PubMed1999

Stability study of human serum albumin pharmaceutical preparations.

The influence of temperature on the stability of human serum albumin (HSA) pharmaceutical preparations has been studied by size-exclusion high-performance liquid chromatography with multi-angle laser-light-scattering detection and by particle-size analysis. The behaviour of HSA in two pharmaceutical preparations stored at different temperatures (40, 55 and 70 degrees C) followed the same pattern--an increase in the relative percentage of dimer (MW 132 000 Da) and aggregate (MW > 200 000 Da), and then a decrease in the concentration of all species and, finally, sudden protein coagulation. These results suggest a time- and temperature-dependent process. At 70 degrees C, monomer only was detected for both preparations; the amount remaining was 83 and 72% for formulations A and B, respectively. Analysis of size-distribution curves also seems to confirm these results. Initially, three distributions were observed with length-volume mean diameters (d1,v) of 1.67, 10.6 and 57 microm. After 80 days at 55 degrees C, only two distributions were observed, with d1,v of 3.07 and 76 microm. An additional study using pure HSA at different concentrations (0.3, 2.5, 5 and 10% w/v) and storage at 75 degrees C was performed to determine the influence of the concentration of auxiliary substances and of the HSA. Only when the HSA concentration was 0.3% w/v did the remaining fraction of HSA fit a Prout-Thompkins nucleation model. Initially three distributions with mean sizes of 2, 20 and 40 microm were observed whereas at the end of the assay only one distribution, mean size 129 microm, was seen. The methodology used enabled us to separate the HSA degradation products and to determine the absolute molecular weight of albumin monomer and dimer. It is possible to conclude that the degradation mechanism for the formulations studied is complex, and that it is possible to fit the degradation data to Prout-Thompkins kinetics only when the concentration of HSA is low enough (0.3% w/v).

Chromatography, High Pressure Liquid↗