Biomedical subjects

Siddhartha Jain

Publications and source records attributed to Siddhartha Jain.

4 recordsLinked to original sources

PubMed2005

Directed cell migration via chemoattractants released from degradable microspheres.

Chemotaxis, cell migration directed by spatial concentration gradients of chemoattractant molecules, is critical for proper function of the immune system. Materials capable of generating defined chemoattractant gradients via controlled release may be useful for the design of improved vaccines and immunotherapies that draw specific cells to an immunization site. To this end, we encapsulated formyl-Nle-Leu-Phe-Nle-Tyr-Lys (fN'LFN'YK) peptides or macrophage inflammatory protein-3alpha (MIP-3alpha or CCL20) in degradable poly(lactide-co-glycolide) microspheres that provided sustained release for more than 2 weeks in vitro. fN'LFN'YK and MIP-3alpha chemoattract dendritic cells (DCs), the key antigen-presenting cells involved in generation of primary immune responses, and their precursors, monocytes. Using an in vitro videomicroscopy migration assay, we detected strong chemotaxis of human monocytes and monocyte-derived DCs through 3D collagen gels toward microspheres releasing fN'LFN'YK. Similarly, microparticles releasing MIP-3alpha were able to attract mouse bone marrow-derived dendritic cells. Strikingly, prolonged attraction of DCs from distances up to 500 microm from the source to the point of contact with individual microspheres was observed. Such microspheres could be of general interest for the design of vaccines that promote adaptive immunity and as a platform for studying the biology of chemotaxis in vitro and in vivo.

Absorbable Implants↗

PubMed2002

Kinetic model for designing a cancer therapy.

A kinetic model has been developed to study cancer growth. Cancer growth has been considered as interaction between various independent but interacting compartments. The model considers cell growth and metastasis resulting in the formation of new tumor masses. Using certain representative parameter values, cell growth has been modeled in the absence and the presence of various cancer therapies. Based on this analysis, the critical parameters involved in cancer development have been identified. This model may thus be useful in studying and designing a cancer therapy using the data obtained from specific in vitro experiments.

Journal Article↗

PubMed2002

Artificial in vivo antigen presentation by the APCs and subsequent T-cell activation: a feasibility analysis.

Inappropriate antigen presentation by the antigen-presenting cells (APCs) is a cause of various diseases. One of the ways to combat these diseases is to immobilize the APCs near the infected tissue or a tissue which is susceptible to an antigen. The antigen is presented by the APCs present in the immobilized form on an implant and these upon binding to T(H)-cells result in triggering of a cascade of events as part of the natural immune response leading to the destruction of the antigen. This system has been modeled as a dialysis bag containing immobilized receptors inside the bag and the ligand diffusing out of the bag. The simulations show that by using the implant, the concentration of the ligand that has diffused into the tissue matrix can be substantially reduced and by suitably choosing the coupler size, the T(H)-cells can also effectively be activated.

Antigen Presentation↗

PubMedDate not supplied

Synthesis of protein-loaded hydrogel particles in an aqueous two-phase system for coincident antigen and CpG oligonucleotide delivery to antigen-presenting cells.

Materials that effectively deliver protein antigens together with activating ligands to antigen-presenting cells are sought for improved nonviral vaccines. To this end, we synthesized protein-loaded poly(ethylene glycol) (PEG)-based hydrogel particles by cross-linking PEG within the polymer-rich phase of an emulsion formed by a poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) triblock copolymer in saturated aqueous salt solution. These particles (500-nm diameter) contained high levels of encapsulated protein (approximately 75% of dry mass), which was selectively released by proteolytic enzymes normally present in the phagosomal/endosomal compartments of dendritic cells (DCs). For co-delivery of cellular activation signals, gel particles were surface-modified by sequential adsorption of poly(l-arginine) and CpG oligonucleotides. DCs pulsed with protein-loaded particles activated naïve T cells in vitro approximately 10-fold more efficiently than DCs incubated with soluble protein. This organic solvent-free strategy for protein encapsulation within submicron-sized hydrophilic particles is attractive for macromolecule delivery to a variety of phagocytic and nonphagocytic cells.

Adsorption↗