Developing a Dissociative Nanocontainer for Peptide Drug Delivery

Patrick Kelly, Prachi Anand, Alexander Uvaydov, Srinivas Chakravartula, Chhime Sherpa, Elena Pires, Alison O’Neil, Trevor Douglas and Mandë Holford
Additional contact information
Patrick Kelly: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA
Prachi Anand: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA
Alexander Uvaydov: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA
Srinivas Chakravartula: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA
Chhime Sherpa: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA
Elena Pires: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA
Alison O’Neil: Stem Cell and Regenerative Biology Department, Harvard University, 7 Divinity Ave, Cambridge, MA 02138, USA
Trevor Douglas: Department of Chemistry, Indiana University, 800 E. Kirkwood Ave., Bloomington, IN 47405, USA
Mandë Holford: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA

IJERPH, 2015, vol. 12, issue 10, 1-13

Abstract: The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB) models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP) reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid) is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.

Keywords: peptide therapeutics; nanocontainers; drug delivery; P22 bacteriophage; viral capsid; ROMP; controlled disassembly; triggered release; Grubbs catalyst; venom peptides (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2015
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