Biomedical subjects

Subbu S Venkatraman

Publications and source records attributed to Subbu S Venkatraman.

9 recordsLinked to original sources

PubMed2006

Sustained release of hydrophobic and hydrophilic drugs from a floating dosage form.

Floating dosage forms enable the sustained delivery of drugs in the gastro-intestinal tract. In this study, a type of multi-unit floating gel bead was synthesized with calcium alginate, sunflower oil, and a drug of interest through an emulsification/gelation process. The alginate beads with oil addition were able to continuously float over the medium for 24h under constant agitation while the non-oily beads could not. Three kinds of drugs with different hydrophilicities, ibuprofen, niacinamide and metoclopramide HCl, were tested in the study. The hydrophobic drug ibuprofen was released in a sustained manner for 24h, due to the oil partitioning. With suitable modification, the beads were able to also release the hydrophilic drugs, niacinamide and metoclopramide HCl, for a similar duration. Therefore a floating dosage form that is able to sustain release both hydrophobic and hydrophilic drugs within its extended gastric retention time has been developed.

Alginates↗

PubMed2006

Controlled release of sirolimus from a multilayered PLGA stent matrix.

The release of sirolimus from a bi-layer biodegradable polymeric film is reported in this study. Approved drug-eluting metal stents use a thin polymer coating to control drug release, but the degree of control is limited. In a fully polymeric stent, the use of multilayers allows a range of release kinetics. A bi-layer system, with PLLA as the supporting layer and PLGA as the drug-eluting layer, was used in this study to simulate release of sirolimus from a stent. The results show that the release of sirolimus is diffusion and degradation-controlled, and that the amount of sirolimus loading does not affect its release kinetics. The release of sirolimus is, however, accelerated by the addition of a plasticizer, such as PEG, as water uptake is increased. An increased water uptake increases polymer degradation, and changes the dominant mode of release to degradation-control. The release of sirolimus can, on the other hand, be retarded by using a coating of a biodegradable polyester with a lauryl ester end group. Therefore, multilayered systems offer many options for controlling sirolimus release over months.

Delayed-Action Preparations↗

PubMed2006

Effect of radio-opaque filler on biodegradable stent properties.

The effect of the addition of a radio-opaque filler, barium sulfate (BaSO(4)), on the mechanical properties of a biodegradable amorphous polymer film (poly-lactic-co-glycolic acid, PLGA) was studied, as a function of degradation. With up to about 18% loading (v/v), the modulus of the filled polymer increases; beyond this concentration, agglomerates are formed. The filled systems are also radio-opaque, over a thickness range of 0.07-0.19 mm in stent form (helicoidal). These stents were then immersed in phosphate buffer pH 7.4 at 37(o)C for 2 weeks. The radial strength of stent was measured by using a compression test. It was found that filler-loaded stent (FS) increased in radial strength by about 4 times (14.95 +/- 1.20 N/mm) compared to the unfilled stent (UFS). However, both samples lost radial strength as the polymer degraded in buffer, but FS retained 60% (9.05 +/- 0.07 N/mm) of its strength after 2 weeks whereas only 36% (1.39 +/- 1.04 N/mm) was retained for UFS. Moreover, UFS lost its helical shape after 3 weeks. The findings have implications for optimization of degradable stent formulations.

Absorbable Implants↗

PubMed2006

Collapse pressures of bilayered biodegradable stents.

Biodegradable helicoidal stent prototypes made up of layers of poly-L-lactic acid (PLLA) and poly(L-lactic-co-glycolic acid) (PLGA) polymers were fabricated by temperature conditioning the stents at different stages of fabrication. The process incorporated elastic memory, or self-expandability in the stent, which is desirable to minimize stent recoil. The collapse pressures of such stents were studied, with and without in vitro degradation. The effects of thickness and the composition of each layer on the collapse pressure were modeled using the simple series model. Results of the in vitro studies for over 3 months showed that collapse pressure of the stents depended mainly on the degradation and other side-effects brought about by the degradation of different polymer compositions. Generally, the trend is dominated by the thicker of the two layers that were used to form the stents.

Absorbable Implants↗

PubMed2005

Micelle-like nanoparticles of star-branched PEO-PLA copolymers as chemotherapeutic carrier.

Four-armed (star-branched) block copolymers of l-PLA and PEO were synthesized using ring opening polymerization with different LA/EO ratio. Micellar aggregates were prepared from these block copolymers and characterized. Some surface segregation of PEG was found : the extent depends on the state of the material (whether it is in film or particle form), as well as on molecular geometry. The degradation behavior of star-shaped copolymer was studied over a three week period and compared to its linear counterpart. Anti-cancer drugs 5-FU and paclitaxel were loaded into the micellar nanoparticles. The drug release profile showed that the release of paclitaxel from these polymers could be controlled over 2 weeks. The kinetics of drug release for star-branched, tri- and di-block copolymers were compared. The micelles from star-shaped branch showed more complete release of drug than the diblock copolymers; also, the lower hydrodynamic radius of star-shaped polymers may result in better clearance of the carrier polymer from the body.

Antineoplastic Agents↗

PubMed2005

Biodegradable stents with elastic memory.

This work reports, for the first time, the development of a fully biodegradable polymeric stent that can self-expand at body temperatures (approximately 37 degrees C), using the concept of elastic memory. This self-expansion is necessary in fully polymeric stents, to overcome the problem of elastic recoil following balloon expansion in a body vessel. Bi-layered biodegradable stent prototypes were produced from poly-L-lactic acid (PLLA) and poly glycolic acid (PLGA) polymers. Elastic memory was imparted to the stents by temperature conditioning. The thickness and composition of each layer in the stents are critical parameters that affect the rate of self-expansion at 37 degrees C, as well as the collapse strengths of the stents. The rate of self-expansion of the stents, as measured at 37 degrees C, exhibits a maximum with layer thickness. The Tg of the outer layer is another significant parameter that affects the overall rate of expansion.

Absorbable Implants↗

PubMed2005

Micelle-like nanoparticles of PLA-PEG-PLA triblock copolymer as chemotherapeutic carrier.

Triblock copolymer PLA-PEG-PLA were synthesized using ring opening polymerization with different LA/EG ratio. Micellar aggregates were prepared from these block copolymers and characterized. The degradation characteristics of selected copolymers were assessed in both micellar and film forms. Surface segregation of PEG was also quantified as a function of copolymer composition. Anti-cancer drugs 5-FU and paclitaxel were loaded into the micellar nanospheres with good efficiency. The drug release profile showed good control over the release of paclitaxel from these polymers.

Drug Carriers↗

PubMed2005

Controlled release from bioerodible polymers: effect of drug type and polymer composition.

The effect of the chemical nature of the drug on matrix degradation and drug release behavior of degradable polymers was studied, using lidocaine as a model drug in base and salt forms. We show in this study that the drug in the base form has a substantial effect on the release characteristics, through an accelerating effect on matrix degradation. Study of drug release from PdlLGA shows that lidocaine salt follows a three-phase release pattern, in contrast to the biphasic release of the lidobase. However, PlLA shows a different drug release pattern, with only a single diffusion phase exhibited for both lidobase and lidosalt. We also demonstrate that the crystallinity of matrix plays an important role on drug release profiles: a crystalline matrix (PlLA IV=2.04) releases the drug at a much slower rate compared to its amorphous counterpart of similar molecular weight (PdlLA IV=2.4). The details of the study of different factors influencing the drug release may have important implications for the control of delivery of potent drugs in various therapeutic windows.

Algorithms↗

PubMed2004

In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices.

We have studied the in vitro release kinetics of two important antirestenosis drugs from biodegradable stent matrices. A helical stent incorporating drugs was exposed to buffer, and both degradation-controlled and diffusion-controlled drug releases were observed. New methods for in vitro drug release for both paclitaxel and rapamycin have been developed. The release profile shows a slow diffusion-controlled phase, followed by a more rapid degradation-controlled region. In the early part of the drug release, no burst effect is observed for either drug. This might be significant for paclitaxel administration, where cardiotoxicity has been sometimes of concern. By suitable polymer/drug formulations, it is possible to develop controlled release stent matrices that can exhibit a variety of release profiles. These release profiles may have relevance to antirestenotic effects and to local or systemic toxic effects.

Paclitaxel↗