Biomedical subjects

Dinesh B Shenoy

Publications and source records attributed to Dinesh B Shenoy.

8 recordsLinked to original sources

PubMed2005

Microgel-based engineered nanostructures and their applicability with template-directed layer-by-layer polyelectrolyte assembly in protein encapsulation.

A novel strategy for the fabrication of microcapsules is elaborated by employing biomacromolecules and a dissolvable template. Calcium carbonate (CaCO(3)) microparticles were used as sacrificial templates for the two-step deposition of polyelectrolyte coatings by surface controlled precipitation (SCP) followed by the layer-by-layer (LbL) adsorption technique to form capsule shells. When sodium alginate was used for inner shell assembly, template decomposition with an acid resulted in simultaneous formation of microgel-like structures due to calcium ion-induced gelation. An extraction of the calcium after further LbL treatment resulted in microcapsules filled with the biopolymer. The hollow as well as the polymer-filled polyelectrolyte capsules were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and scanning force microscopy (SFM). The results demonstrated multiple functionalities of the CaCO(3) core - as supporting template, porous core for increased polymer accommodation/immobilization, and as a source of shell-hardening material. The LbL treatment of the core-inner shell assembly resulted in further surface stabilization of the capsule wall and supplementation of a nanostructured diffusion barrier for encapsulated material. The polymer forming the inner shell governs the chemistry of the capsule interior and could be engineered to obtain a matrix for protein/drug encapsulation or immobilization. The outer shell could be used to precisely tune the properties of the capsule wall and exterior. [Diagram: see text] Confocal laser scanning microscopy (CLSM) image of microcapsules (insert is after treating with rhodamine 6G to stain the capsule wall).

Alginates↗

PubMed2005

Poly(ethylene oxide)-modified poly(epsilon-caprolactone) nanoparticles for targeted delivery of tamoxifen in breast cancer.

This study was carried out to evaluate and compare the biodistribution profile of tamoxifen when administered intravenously (i.v.) as a simple solution or when encapsulated in polymeric nanoparticulate formulations, with or without surface-stabilizing agents. Tamoxifen-loaded, poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were prepared by solvent displacement process that allowed in situ surface modification via physical adsorption of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock polymeric stabilizer (Pluronic). The nanoparticles were characterized for particle size and surface charge. Presence of PEO chains on nanoparticle surface was ascertained by electron spectroscopy for chemical analysis (ESCA). In vivo biodistribution studies were carried out in Nu/Nu athymic mice bearing a human breast carcinoma xenograft, MDA-MB-231 using tritiated [(3)H]-tamoxifen as radio-marker for quantification. PEO-PCL nanoparticles with an average diameter of 150-250 nm, having a smooth spherical shape, and a positive surface charge were obtained with the formulation procedure. About 90% drug encapsulation efficiency was achieved when tamoxifen was loaded at 10% by weight of the polymer. Aqueous wettability, suspendability, and ESCA results showed surface hydrophilization of the PCL nanoparticles by the Pluronics. The primary site of accumulation for the drug-loaded nanoparticles after i.v. administration was the liver, though up to 26% of the total activity could be recovered in tumor at 6h post-injection for PEO-modified nanoparticles. PEO-PCL nanoparticles exhibited significantly increased level of accumulation of the drug within tumor with time as well as extended their presence in the systemic circulation than the controls (unmodified nanoparticles or the solution form). Pluronic surfactants (F-68 and F-108) presented simple means for efficient surface modification and stabilization of PCL nanoparticles to achieve preferential tumor-targeting and a circulating drug reservoir for tamoxifen.

Animals↗

PubMed2004

Phase structures of a hydrated anionic phospholipid composition containing cationic dendrimers and pegylated lipids.

The effect of 4th generation poly(amidoamine) dendrimer (4G PAMAM) present in an anionic phospholipid composition, consisting of hydrogenated soyphosphatidylcholine (HSPC), cholesterol (CH), dicetyl phosphate (DCP), and poly(ethylene glycol) (Mw approximately 2000) derivatized phosphatidylethanolamine (PEG2000-PE), on the hydration and liquid crystalline structure formation was investigated. The optical and polarized light microscopies of the liposomal dispersion obtained from the hydrated lipid composition show two types of birefringent structures (mesophases): plastic, wormlike microstructures and conventional, over-elongated lamellae. Differential scanning calorimetry (DSC) shows an increase in the liquid crystalline phase transition (Tg) of the lipid composition from 60 to 94 degrees C with increasing 4G PAMAM concentrations from 0 to 0.011 mM, respectively. The Tg values of the two microstructures were 68 and 84 degrees C, respectively, indicating that the plastic microstructures were 4G PAMAM/DCP-complexes-rich (alpha mesophases) and the conventional and elongated lamellae were dendrimer-doped HSPC/CH-rich microstructures (beta mesophases). Optical microscopy shows that the alpha mesophases convert into various other types of vesicular structures such as giant unilamellar vesicles and biliquid foams, upon heating above the phase transition temperature of the lipid composition (approximately 60-65 degrees C). The microstructure transformation is a result of an osmotic influx of water and the detergent action of PEG2000-PE present in the lipid composition. The transmission electron microscopy (TEM) images of the liposomal dispersion show particles embedding circular transparent domains that exactly correlate to the theoretical 4G PAMAM/DCP complex sizes, thus, providing evidence of 4G PAMAM interspersed within the two mesophases. Small-angle X-ray scattering (SAXS) measurements indicate that the alpha mesophases are a dendrimer-interlinked, symmetrically undulated lamellar phase and the beta mesophases are dendrimer-doped, occasionally kinked lamellae. An increase in dendrimer concentration in the lipid composition was found to decrease interlamellar spacing. On the basis of optical microscopy, DSC, TEM, and SAXS data, a model of dendrimer-doped mesophase structure and lamellae fusion is proposed. This investigation provides new self-assembled materials for drug/gene delivery and supplements the understanding of mechanisms involved in various biological processes such as membrane fusion, transmembrane permeation, and endocytosis.

Calorimetry, Differential Scanning↗

PubMed2004

Engineered microcrystals for direct surface modification with layer-by-layer technique for optimized dissolution.

This investigation relates to a two-step formulation development technique-synthesis of sterically stabilized drug microcrystals followed by direct surface modification by sequential electrostatic adsorption. Stable microcrystals of naproxen were produced by pH-induced reprecipitation in presence of a stabilizer. Sequential layer growth was achieved by the layer-by-layer assembly of biocompatible polyelectrolytes (PEs) and was registered using microelectrophoresis. The coated colloids were characterized using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The in vitro controlled release pattern of the drug through the PE diffusion barrier was studied using a diffusion cell assembly at physiological pH of 7.4, both before and after freeze-drying. Thermodynamically stable naproxen microcrystals were obtained by association and had a mean length of 15 microm and a zeta potential of -37.5 mV and were surface modified efficiently using biocompatible polysaccharide/protein-based PEs. Sufficient charge reversal with each layer was evident indicating layer growth with successive deposition cycles. The coating was complete and homogeneous as visualized under CLSM and SEM. The in vitro release study revealed that the stoichiometry of PEs in the complex coating and its molecular architecture played important roles in forming the diffusion barrier, which offered efficient control of the dissolution rate of drug core (up to 50% lower than bare crystal). The release profile fitted zero order release kinetics. This novel formulation technique enables administration of high concentrations of water-insoluble drugs in a stable, tissue compatible form, simultaneously affording sustained release.

Chemical Engineering↗

PubMed2003

Potential applications of polymeric microsphere suspension as subcutaneous depot for insulin.

The objective of this investigation was to develop an injectable, depot-forming drug delivery system for insulin based on microparticle technology to maintain constant plasma drug concentrations over prolonged period of time for the effective control blood sugar levels. Formulations were optimized with two well-characterized biodegradable polymers namely, poly(DL-lactide-co-glycolide) and poly-epsilon-caprolactone and evaluated in vitro for physicochemical characteristics, drug release in phosphate buffered saline (pH 7.4), and evaluated in vivo in streptozotocin-induced hypoglycemic rats. With a large volume of internal aqueous phase during w/o/w double emulsion solvent evaporation process and high molecular weight of the polymers used, we could not achieve high drug capture and precise control over subsequent release within the study period of 60 days. However, this investigation revealed that upon subcutaneous injection, the biodegradable depot-forming polymeric microspheres controlled the drug release and plasma sugar levels more efficiently than plain insulin injection. Preliminary pharmacokinetic evaluation exhibited steady plasma insulin concentration during the study period. These formulations, with their reduced frequency of administration and better control over drug disposition, may provide an economic benefit to the user compared with products currently available for diabetes control.

Animals↗

PubMed2002

Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation.

In order to examine the efficacy of paclitaxel (Taxol, Bristol-Myers Squibb) after administration locally at the tumor site, we have developed a thermo-reversible gelling formulation in poloxamer 407 (Pluronic F-127) solution. Paclitaxel was incorporated in poloxamer 407 [20% (w/w)] at 0.5- and 1.0-mg/mL concentrations. The in vitro release studies were carried out in phosphate-buffered saline (pH 7.4) at 37 degrees C. Control and paclitaxel-poloxamer 407 formulations were administered intratumorally at a dose of 20 mg/kg in B16F1 melanoma-bearing mice. The change in tumor volume as a function of time and the survival of treated animals were used as measures of efficacy. Poloxamer 407 solution undergoes a reversible sol-gel transition when the temperature is raised to above 21 degrees C. In vitro paclitaxel release from poloxamer 407 gels was very slow (only 6.1% after 6 hr) probably due to the poor aqueous solubility of the drug. Significant enhancement in the anti-tumor efficacy was noted following intratumoral administration of paclitaxel-poloxamer 407 formulation. The initial tumor growth rate was delayed by 67% and the tumor volume doubling time was increased by 72% relative to saline control. In addition, more than 91% of the tumor-bearing animals that received paclitaxel in poloxamer 407 gel survived on day 15 post-administration as compared to 58% in the control group. The results of this study show significant benefit of paclitaxel for solid tumor when administered locally in an in situ gelling poloxamer 407 formulation.

Animals↗

PubMed2002

Biodegradable microspheres of curcumin for treatment of inflammation.

Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7) was formulated as prolonged release biodegradable microspheres for treatment of inflammation. Natural biodegradable polymers, namely, bovine serum albumin and chitosan were used to encapsulate curcumin to form a depot forming drug delivery system. Microspheres were prepared by emulsion-solvent evaporation method coupled with chemical cross-linking of the natural polymers. Curcumin could be encapsulated into the biodegradable carriers upto an extent of 79.49 and 39.66% respectively with albumin and chitosan. Different drug:polymer ratios did not affect the mean particle size or particle size distribution significantly. However, the concentration of the crosslinking agent had remarkable influence on the drug release. In-vitro release studies indicated a biphasic drug release pattern, characterized by a typical burst-effect followed by a slow release which continued for several days. Evaluation of antinflammatory activity using Freund's adjuvant induced arthritic model in Wistar rats revealed significant difference between both the formulations, albumin microspheres and chitosan micropheres as well as against control. It was evident from the present study that the curcumin biodegradable microspheres could be successfully employed as prolonged release drug delivery system for better therapeutic management of inflammation as compared to oral or subcutaneous route.

Absorbable Implants↗

PubMedDate not supplied

Layer-by-layer engineering of biocompatible, decomposable core-shell structures.

The objective of the present investigation was to fabricate composite colloidal particles consisting of a sacrificial, decomposable template of biodegradable nature covered with biocompatible polyelectrolyte multilayers using the layer-by-layer sequential adsorption technique. Poly-dl-lactic acid and poly(dl-lactic-co-glycolic acid) were chosen to design the microparticulate template, and a preliminary feasibility study was carried out with poly(styrene sulfonate sodium)-poly(allylamine hydrochloride) as shell components. The properties of both core-shell and hollow structures obtained by core dissolution were characterized by confocal laser scanning microscopy, microelectrophoresis, scanning force microscopy, and scanning electron microscopy. The concept was then extended to biocompatible polyelectrolytes as shell wall building blocks to deduce stable hollow capsules with tailored properties. Uniform, complete coating with oppositely charged polyelectrolyte pairs was achieved for all the combinations investigated. The results demonstrate that polyester microparticles could serve as viable alternative components to conventionally employed templates to derive hollow capsules with defined size, shape, and shell thickness. With all the components used for fabrication being biocompatible, these polyelectrolyte capsules may find interesting applications in the fields of biology, biochemistry, biotechnology, and drug delivery.

Biocompatible Materials↗