Biomedical subjects

Sadhana Sharma

Publications and source records attributed to Sadhana Sharma.

8 recordsLinked to original sources

PubMed2006

Controlled-release microchips.

Efficient drug delivery remains an important challenge in medicine: continuous release of therapeutic agents over extended time periods in accordance with a predetermined temporal profile; local delivery at a constant rate to the tumour microenvironment to overcome much of the systemic toxicity and to improve antitumour efficacy; improved ease of administration, and increasing patient compliance required are some of the unmet needs of the present drug delivery technology. Microfabrication technology has enabled the development of novel controlled-release microchips with capabilities not present in the current treatment modalities. In this review, the current status and future prospects of different types of controlled-release microchips are summarised and analysed with reference to microneedle-based microchips, as well as providing an in-depth focus on microreservoir-based and nanoporous microchips.

Animals↗

PubMed2005

Release of biologically functional interferon-alpha from a nanochannel delivery system.

Metastatic melanoma lesions often are unresectable due to their size and/or location near critical structures. These lesions represent a significant challenge for the oncologist, because radiation therapy and chemotherapy are infrequently successful in halting tumor growth. Of primary concern is the fact that these lesions are usually painful and present a cosmetic dilemma. We hypothesized that the development of a silicon-based nano-device capable of delivering antitumor compounds (e.g. immune modulators), locally, at a constant rate, to the tumor microenvironment could avoid the toxicity of systemic administration and the inconvenience of frequent clinic visits for local injections. Because of its diminutive size, such a device could be implanted using a minimally invasive procedure in close proximity to unresectable melanoma lesions. The current report uses interferon alpha-2b (IFN-alpha) as a model antitumor agent, since it is commonly used in the treatment of malignant melanoma and metastatic renal cell carcinoma. In this system, IFN-alpha is delivered directly to the tumor microenvironment by a novel nanochannel delivery system (nDS) that is capable of zero order release of small molecules. We have demonstrated that the IFN-alpha released from the nDS is functionally active on both host immune cells and a human melanoma cell line in vitro. This drug delivery platform could be used to develop alternative strategies for the treatment of unresectable tumors.

Antineoplastic Agents↗

PubMed2005

Nanostructured antifouling poly(ethylene glycol) films for silicon-based microsystems.

The creation of antifouling surfaces is one of the major prerequisites for silicon-based micro-electrical-mechanical systems for biomedical and analytical applications (known as BioMEMS). Poly(ethylene glycol) (PEG), a water-soluble, nontoxic, and nonimmunogenic polymer has the unique ability to reduce nonspecific protein adsorption and cell adhesion and, therefore, is generally coupled with a wide variety of surfaces to improve their biocompatibility. To this end, we have analyzed PEG thin films of various grafting densities (i.e., number of PEG chains per unit area) coupled to silicon using a single-step PEG-silane coupling reaction scheme using variable-angle ellipsometry. Initial PEG concentration and coupling time were varied to attain different grafting densities. These data were theoretically analyzed to understand the phenomenon of PEG film formation. Furthermore, all the PEG films were evaluated for their ability to control biofouling using albumin and fibrinogen as the model proteins. PEG thin films formed by using higher PEG concentrations ( > or = 10 mM PEG) or coupling time ( > or = 1 h) demonstrated enhanced protein fouling resistance behavior. This analysis is expected to be useful to form PEG films of desired grafting density on silicon substrates for appropriate application.

Adsorption↗

PubMed2004

XPS and AFM analysis of antifouling PEG interfaces for microfabricated silicon biosensors.

In the past two decades, the biological and medical fields have seen great advances in the development of biosensors capable of quantifying biomolecules. Many of these biosensors have micro- and nano-scale features, are fabricated using biochip technology, and use silicon as a base material. The creation of antifouling sensor interfaces is critical to avoid serious consequences that arise due to their contact with biological fluids. To this end, we have created thin PEG interfaces of various grafting densities on silicon using a single-step PEG-silane coupling reaction scheme. Initial PEG concentration (5-50 mM) and coupling time (0.5-24 h) were varied to attain different grafting densities, and different PEG interfaces so created were analyzed using XPS and AFM. Furthermore, all the PEG interfaces were evaluated using XPS and AFM for their antifouling abilities using fibrinogen as the model protein. Results indicated that PEG interfaces created in this investigation are appropriate for biosensors with micro- and nano-scale features, and are efficient in controlling protein fouling.

Biosensing Techniques↗

PubMed2004

Evaluation of the stability of nonfouling ultrathin poly(ethylene glycol) films for silicon-based microdevices.

The creation of nonfouling surfaces is one of the major prerequisites for microdevices for biomedical and analytical applications. Poly(ethylene glycol) (PEG), a water soluble, nontoxic, and nonimmunogenic polymer has the unique ability of reducing nonspecific protein adsorption and cell adhesion and, therefore, is generally coupled with a wide variety of surfaces to improve their biocompatibility. The performance of these modified surfaces for long-term biomedical applications largely depends on the stability of these PEG films. To this end, we have investigated the stability of covalently coupled ultrathin PEG films on silicon in aqueous in vivo like conditions for a period of 4 weeks. The PEG-modified silicon substrates were incubated in PBS (37 degrees C, pH 7.4, 5% CO2) for different periods of time and then characterized using the techniques of ellipsometry, contact angle measurement, X-ray photoelectron spectroscopy, and atomic force microscopy. The ability of the PEG-modified surfaces to control protein fouling was examined by protein adsorption studies using fluorescein isothiocyanate labeled bovine serum albumin and ellipsometry. Furthermore, the ability of these films to control fibroblast adhesion was examined. Studies suggest that the PEG-modified surfaces retain their protein and cell repulsive nature even though the PEG film thickness decreases for the period of investigation.

Biocompatible Materials↗

PubMed2002

The lumicins: novel bacteriocins from Photorhabdus luminescens with similarity to the uropathogenic-specific protein (USP) from uropathogenic Escherichia coli.

Bacteriocins are proteins produced by bacteria to destroy other bacteria occupying their ecological niche. Photorhabdus luminescens is an insect pathogenic bacterium carried by an entomopathogenic nematode and occupies several different niches in its life cycle. The nematode enters the insect and releases a single strain of P. luminescens. The bacteria then kill the host and the bacteria and nematodes replicate within the cadaver. Strikingly, at the end of the infection the cadaver is still occupied by a single strain of bacterium, suggesting that P. luminescens can destroy other bacteria entering, or present within, the insect. Here we describe four loci encoding 'lumicins' in P. luminescens subsp. akhurstii strain W14. The lumicins are novel bacteriocins capable of killing other strains of Photorhabdus and Escherichia coli. These loci predict killer proteins and multiple dual type immunity proteins with domains similar to pyocins and colicins. The killer proteins are chimeric in nature with multiple domains, one of which is similar to the uropathogenic-specific protein (USP) described from uropathogenic E. coli. The implications of these novel bacteriocins for the lifestyle of Photorhabdus and the potential role of USP as a bacteriocin in E. coli are discussed.

Amino Acid Sequence↗

PubMed2002

Bacterial infection of a model insect: Photorhabdus luminescens and Manduca sexta.

Invertebrates, including insects, are being developed as model systems for the study of bacterial virulence. However, we understand little of the interaction between bacteria and specific invertebrate tissues or the immune system. To establish an infection model for Photorhabdus, which is released directly into the insect blood system by its nematode symbiont, we document the number and location of recoverable bacteria found during infection of Manduca sexta. After injection into the insect larva, P. luminescens multiplies in both the midgut and haemolymph, only later colonizing the fat body and the remaining tissues of the cadaver. Bacteria persist by suppressing haemocyte-mediated phagocytosis and culture supernatants grown in vitro, as well as plasma from infected insects, suppress phagocytosis of P. luminescens. Using GFP-labelled bacteria, we show that colonization of the gut begins at the anterior of the midgut and proceeds posteriorly. Within the midgut, P. luminescens occupies a specific niche between the extracellular matrix and basal membrane (lamina) of the folded midgut epithelium. Here, the bacteria express the gut-active Toxin complex A (Tca) and an RTX-like metalloprotease PrtA. This close association of the bacteria with the gut, and the production of toxins and protease, triggers a massive programmed cell death of the midgut epithelium.

Animals↗

PubMedDate not supplied

Improving the integrity of three-dimensional vascular patterns by poly(ethylene glycol) conjugation.

Development of functional tissue-engineering constructs may require that multiple cell types be organized in controlled three-dimensional (3-D) microarchitectures with proper nutrient diffusion and vascularization. In the past few years, a variety of microscale techniques have demonstrated the ability to control protein and cell attachment in defined patterns. Nevertheless, maintenance of these patterns over time has been a significant challenge due to nonspecific protein adsorption and cell migration. To this end, we have investigated the effectiveness of poly(ethylene glycol) (PEG) thin films in maintaining the integrity of 3-D cellular patterns, using human umbilical vein endothelial cells (HUVEC) as a model system. These HUVEC constructs were created using extracellular matrix (ECM)-based microfluidic patterning. Our results indicated that PEG-conjugated substrates improve cell pattern integrity as compared to control silicon. The compliance multifactor (a measure of pattern integrity; higher value means lower pattern integrity) was about 3.66 +/- 0.29 on day 5 for PEG-conjugated surfaces, compared with 8.23 +/- 0.42 for control surfaces ECM-based microfluidic patterning coupled with stable PEG-conjugated surfaces may serve as a vital tool for vascularized tissue engineering.

Cells, Cultured↗