Oral administration of peptide and protein drugs requires their protection from the acidic and enzymatic degradation in the gastro-intestinal environment and their targeting to the absorption zone. For this purpose, an alginate microsystem, as a carrier of bovine serum albumin (BSA), as a model protein, was developed using a spray-drying technique. A hardening process with Ca2+ and chitosan (CS) provided a system with resistance to the gastro-intestinal barriers and of appropriate size for targeting to the Peyer's patches. The present work aims to evaluate the effects of the ratio of sodium alginate (Na-A) and BSA as well as the pH of the crosslinking medium on the microsystem properties. Microparticle morphological and dimensional characteristics did not change significantly with the formulation variables. BSA loading at a pH value less than the protein isoelectric point (pI) was higher than that at a pH similar to the pI owing to an electrostatic interaction between the charged protein and the polyanionic alginate. The maximum encapsulation efficiency was obtained at the highest Na-A/BSA ratio. Protein release in a simulated gastro-intestinal fluid was not affected by the preparative variables, but was controlled by the pH-dependent nature of the polymer material. Polyacrylamide gel electrophoresis (PAGE) demonstrated the stability of the protein to both the preparative conditions and the gastro-intestinal pH values.

Alginates↗

PubMedDate not supplied

Influence of drug loading level on drug release and dynamic swelling of crosslinked gelatin microspheres.

The effect of drug loading level both on dynamic swelling and drug release was evaluated using crosslinked gelatin microspheres. Owing to water penetration the microsphere diameter went first to a maximum value, which was not affected by the payload; the diameter gradually approached to an equilibrium swollen value, which was affected by drug loading level. Water absorption increases and drug diffusion decreases the microsphere diameter. Obviously, the diameter variation depends on the factor (water absorption or drug diffusion) predominating in the process. As the payload affected only the equilibrium swollen value it is reasonable to hypothesize that drug loading level has a greater effect on drug diffusion than on polymer relaxation. This rationale could explain the increase of the diffusion component of the drug release process as the payload increased.

Aminophylline↗

PubMedDate not supplied

Analysis of release data in the evaluation of the physical state of progesterone in matrix systems.

Ethylene-vinyl acetate microspheres were prepared by an emulsion solvent-evaporation method as sustained delivery carriers of progesterone. Physical state of the drug in the microspheres was affected by drug loading level. As thermal analysis and mathematical release models showed, low payloads of the matrix supported the molecularly dispersed drug. Crystalline drug appeared only as the drug loading level increased. The release process of the crystalline drug produced a porosity increase in the polymeric system; thus, the drug could diffuse through pores and channels. Hence, the porosity of the matrix structure was affected by the payload. This hypothesis could justify the increasing goodness-of-fit of the release data to the square-root model as the drug loading level of the microspheres increased.

Calorimetry, Differential Scanning↗

PubMedDate not supplied

The concentration of the cross-linking agent as a tool for the control of release and swelling properties of gelatin microspheres.

The effect of the concentration of a cross-linking agent (gelatin hardener) on gelatin microspheres was evaluated. A concentration increase of the gelatin hardener (formaldehyde) produced a decrease of drug loading, swelling degree and drug release rate. The cross-linking agent concentration affected also the kinetics of water absorption and drug release. This paper suggests a decreasing significance of the diffusion-type mechanism of drug release as the concentration of the cross-linking agent increased.

Capsules↗

PubMedDate not supplied

General and cardiac toxicity of doxorubicin-loaded gelatin nanoparticles.

General and cardiac toxicity of doxorubicin loaded gelatin nanoparticles cross-linked by glutaraldheyde were investigated in healthy rats. The rats were treated with free doxorubicin (DXR), unloaded nanoparticles (UNp), physical mixture of doxorubicin and unloaded nanoparticles (DRX/UNp), and DXR-loaded nanoparticles (DXR-Np). Each group of animals received the same dose of DXR (3 mg/kg) via i.p. once a week. Both electrocardiogram (ECG) parameters and body weight were measured 24 h before each administration. Rats treated with UNp behaved as controls. DXR/UNp provoked the same toxic effects as free DXR. On the contrary, DXR-Np resulted more toxic since significant variations of both the body weight and the ECG parameters were observed during the first week of treatment. In addition, the rats treated with DXR-Np died between the 3rd and the 5th day after the 2nd administration. These results demonstrate that, in these experimental conditions, the couplage of DXR to nanoparticles enhanced the cardiotoxicity of the drug. Since DXR was linked to the protein matrix of nanoparticles via glutaraldehyde, the high toxicity of DXR-loaded nanoparticles could be due to the covalent binding of the drug to the carrier.

Animals↗