Biomedical subjects

Lothar Kleiner

Publications and source records attributed to Lothar Kleiner.

3 recordsLinked to original sources

PubMed2005

Structure formation in injectable poly(lactide-co-glycolide) depots. II. Nature of the gel.

The benzyl benzoate solutions of poly(D,L-lactide-co-glycolide), a random oriented synthesized copolymer with L/G ratio of 50:50, have been shown to form gels during aging and upon injection into buffer or water. The gelation properties influence drug release kinetics for these injectable, depot-forming solutions. In this article, we report on the mechanism of gelation. We find that only polymers that have a certain average block length of glycolide units form gels during aging as well as depots upon in vitro. Thus, gel formation is likely due to the formation of ordered solvated aggregates of blocky glycolide units. Rheometry, differential scanning calorimetry, and nuclear magnetic resonance were used to investigate the gelation kinetics and the polymer molecular parameters. Of all the polymers used, poly(lactide-co-glycolide)s with glycolide average block length <2.9 did not show any gelation behavior. The details of the gelation process are also solvent dependent.

Calorimetry, Differential Scanning↗

PubMed2004

Drug release from injectable depots: two different in vitro mechanisms.

Certain poly (lactide-co-glycolide) (PLGA)/benzyl benzoate (BB) solutions can form gels when injected into buffer (depot formation) as well as upon ageing under ambient conditions. When evaluating various PLGAs in benzyl benzoate, we have found that only those that gel upon ageing also form gel depots in buffer. This indicates that depot formation in this system may be fundamentally different from the phase inversion depot formation that has been observed for PLGA in water-miscible solvents. The drug release kinetics in vitro is controlled both by diffusion and erosion, with the base form of the drug being always released faster than its salt form. This is due to base-catalyzed hydrolysis. While gel permeation chromatography (GPC) measurements show a continuous decrease in molecular weight, the rheological properties upon buffer injection show maxima, for the base drug and the salt drug. The location of the viscosity maximum with time is dependent on the nature of the drug and its concentration.

Benzoates↗

PubMed2003

Structure formation in injectable poly(lactide-co-glycolide) depots.

Solutions of low-molecular-weight poly(lactide-co-glycolide) (PLGA) in organic solvents have been investigated as novel injectable drug depots for drug delivery over periods of weeks to months. In this paper, we investigated the structure formation in a PLGA/benzyl benzoate system, using controlled stress rheometry, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). GPC analysis demonstrated a decrease in molecular weight as a function of time and temperature, indicating degradation. Rheological experiments showed that the flow properties of PLGA/benzyl benzoate solutions were affected by a combination of degradation and gelation; the latter was also detected by an endotherm in DSC and by three-dimensional structure formation studies by rheology. Extent of degradation and gelation of PLGA were shown to depend on the solvent.

Benzoates↗