Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alz... more Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues.
Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a sign... more Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a significant hurdle in using nanomedicine for treating hemorrhage, thrombosis, and atherosclerosis. While several types of nanoparticles have been developed to meet this goal, their utility is limited by poor circulation, limited margination, and minimal targeting. Platelets have an innate ability to marginate to the vascular wall and specifically interact with vascular injury sites. These platelet functions are mediated by their shape, flexibility, and complex surface interactions. Inspired by this, we report the design and evaluation of nanoparticles that exhibit platelet-like functions including vascular injury site-directed margination, site-specific adhesion, and amplification of injury site-specific aggregation. Our nanoparticles mimic four key attributes of platelets, (i) discoidal morphology, (ii) mechanical flexibility, (iii) biophysically and biochemically mediated aggregation, and ...
Journal of controlled release : official journal of the Controlled Release Society, Jan 10, 2015
Cyclosporine A (CsA) is used for the treatment of psoriasis; however systemic administration of C... more Cyclosporine A (CsA) is used for the treatment of psoriasis; however systemic administration of CsA is potentially life threatening and there are long-term side effects. Topical application of CsA has the potential to overcome this hurdle; however, its use is limited by poor water solubility and low permeability. Here, we report the use of a physical mixture of SPACE-peptide and CsA in an aqueous ethanol solution to enhance the dermal absorption of the drug. The aqueous ethanol solution (hydroethanolic solution) containing 5mg/mL CsA and 50mg/mL of free SPACE-peptide (SP50) delivered about 30% of topically applied CsA into the porcine skin in vitro and led to an approximately 9-fold (p<0.01) increase in accumulation in viable epidermis compared to the hydroethanolic solution without SPACE-peptide (control group). In vivo biodistribution and pharmacokinetic studies performed using SKH1 hairless mice also confirmed the efficacy of SP50 in dermal delivery of CsA and also demonstrate...
Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alz... more Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer's disease, Parkinson's disease, and arthritis, represents one of the major challenges in drug delivery. Monocytes possess a unique ability to target and penetrate into sites of inflammation. Here, we describe a broad approach to take advantage of the natural ability of monocytes to target and deliver flat polymeric particles ("Cellular Backpacks") to inflamed tissues. Cellular backpacks attach strongly to the surface of monocytes but do not undergo phagocytosis due to backpack's size, disk-like shape and flexibility. Following attachment of backpacks, monocytes retain important cellular functions including transmigration through an endothelial monolayer and differentiation into macrophages. In two separate in vivo inflammation models, backpack-laden monocytes exhibit increased targeting to inflamed tissues. Cellular backpacks, and their abilities to attach to monocytes without impairing monocyte functions and 'hitchhike' to a variety of inflamed tissues, offer a new platform for both cell-mediated therapies and broad targeting of inflamed tissues.
Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a sign... more Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a significant hurdle in using nanomedicine for treating hemorrhage, thrombosis, and atherosclerosis. While several types of nanoparticles have been developed to meet this goal, their utility is limited by poor circulation, limited margination, and minimal targeting. Platelets have an innate ability to marginate to the vascular wall and specifically interact with vascular injury sites. These platelet functions are mediated by their shape, flexibility, and complex surface interactions. Inspired by this, we report the design and evaluation of nanoparticles that exhibit platelet-like functions including vascular injury site-directed margination, site-specific adhesion, and amplification of injury site-specific aggregation. Our nanoparticles mimic four key attributes of platelets, (i) discoidal morphology, (ii) mechanical flexibility, (iii) biophysically and biochemically mediated aggregation, and ...
Journal of controlled release : official journal of the Controlled Release Society, Jan 10, 2015
Cyclosporine A (CsA) is used for the treatment of psoriasis; however systemic administration of C... more Cyclosporine A (CsA) is used for the treatment of psoriasis; however systemic administration of CsA is potentially life threatening and there are long-term side effects. Topical application of CsA has the potential to overcome this hurdle; however, its use is limited by poor water solubility and low permeability. Here, we report the use of a physical mixture of SPACE-peptide and CsA in an aqueous ethanol solution to enhance the dermal absorption of the drug. The aqueous ethanol solution (hydroethanolic solution) containing 5mg/mL CsA and 50mg/mL of free SPACE-peptide (SP50) delivered about 30% of topically applied CsA into the porcine skin in vitro and led to an approximately 9-fold (p<0.01) increase in accumulation in viable epidermis compared to the hydroethanolic solution without SPACE-peptide (control group). In vivo biodistribution and pharmacokinetic studies performed using SKH1 hairless mice also confirmed the efficacy of SP50 in dermal delivery of CsA and also demonstrate...
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Papers by Sunny Kumar