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Published on: June 23, 2018
Micelle-Based Nanocarriers for Targeted Delivery of Cargo to Pancreas
Swati Mishra1,2, Philip R Streeter3
1Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University, Portland, OR, USA. mishra@ohsu.edu.
Abstract:
Innovations in the field of amphiphilic block copolymers have led to the development of a series of attractive polymer-based drug and gene delivery micellar formulations. The amphiphilic block copolymers' low critical micelle concentration (CMC) results in highly stable nanoscale micelles possessing favorable in vivo safety profiles and biocompatibility, making them an excellent carrier choice for the systemic administration of various poorly soluble drugs. These micelles can also be used as an actively targeted drug delivery system. The targeting is achieved by conjugating specific targeting ligand molecules to the micelle surface. The conjugation takes place at the hydrophilic termini of the copolymers, which forms the shell or surface of the nanomicelles. In our lab, we have developed a targeted Pluronic® F127-based nanoformulation to achieve targeting of specific cell types in the pancreas. To achieve active targeting based on the desired end application, we have conjugated several monoclonal antibodies (~150 kDa IgG) reactive to specific cell types in the pancreas by coupling lysine amino groups of the antibody to the p-nitrophenyl carbonate groups generated on the hydrophilic PEO segments of the Pluronic® F127. The resultant targeted nanomicelles demonstrated high binding specificity and targeting efficiency. These nanomicelles can be used to encapsulate and deliver hydrophobic imaging agents and/or water-insoluble therapeutic small molecules to specific pancreatic cell types, enabling the development of diverse tools for use in the diagnosis and/or treatment of pancreas pathologies.

