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Biomedical subjects

Subbu Venkatraman

Publications and source records attributed to Subbu Venkatraman.

6 recordsLinked to original sources

ABA and BAB type triblock copolymers of PEG and PLA: a comparative study of drug release properties and "stealth" particle characteristics.

We synthesized two types of triblock copolymers containing PEG and PLA as controlled release carriers of hydrophobic drugs: these are the ABA type (PLA-PEG-PLA) and the BAB type (PEG-PLA-PEG). These polymers are amphiphilic and can form nanomicelles (40-200nm) in aqueous medium. On the surface of PLA-PEG-PLA (ABA) type nanomicelles, the PEG content was enhanced somewhat over the bulk amount; whereas in the PEG-PLA-PEG (BAB type), surface segregation was much higher. The copolymers tested can entrap 35% of paclitaxel by weight on the average. In general, the diffusion-controlled release of paclitaxel is slower for the BAB polymers; furthermore, the actual release rates are influenced by the PLLA lengths in the BAB copolymers. Surface PEG contents influence the "stealth" characteristics of the nanomicelles. Compared with PLA particles, all nanomicellar particles tested, of both BAB and ABA types, showed a four-fold reduction in monocyte cell uptake, with the BAB type copolymer exhibiting a lesser uptake.

Delayed-Action Preparations↗

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↗

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↗

Study of the initial stages of drug release from a degradable matrix of poly(d,l-lactide-co-glycolide).

The initial stages of the in vitro degradation of and the drug release from a matrix made of poly(d,l-lactide-co-glycolide) was carried out in a phosphate buffer saline (pH 7.0) medium. It has been observed that substantial matrix degradation occurs at the end of 2 weeks of immersion. The drug release using films of the polymer shows a tri-phasic pattern, unlike the bi-phasic patterns usually seen. Mechanisms are proposed for each phase of release, based on results from weight loss, amount of water absorption and scanning electron microscopy. The details of the structural changes and their effects on drug release may have implications for delivering potent drugs over a 2-week period.

Absorbable Implants↗

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↗

Collapse pressures of biodegradable stents.

Biodegradable stent prototypes were produced from poly L-lactic acid polymers with different molecular weights. The effects of molecular weight, drug incorporation and stent design on the collapse pressure of the stents were evaluated. While molecular weights did not show a significant effect on the collapse pressure of the stents, drug incorporation at high percentage decreased the collapse pressure of the stents substantially. Cryogenic fracture surfaces showed significant drug agglomeration as the concentration increased. The design of the stent was also found to a have significant effect on the collapse pressure. The stent produced from the same material has a higher collapse pressure when the load bearing surface area is increased.

Absorbable Implants↗