title: Synthesis and characterization of polymer nanocarriers for the targeted delivery of therapeutic enzymes.
abstract: Protein drugs, such as recombinant enzymes useful for detoxification and replacement therapies, have extraordinary specificity and potency. However, inherently inadequate delivery to target sites and rapid inactivation limit their medical utility. Using chaperone polymeric particles designed within an injectible size range (sub-micron) may help solve these shortcomings. Such nanocarriers would (i) prevent premature inactivation of encapsulated therapeutic protein cargoes, (ii) provide a carrier that can be surface decorated by targeting ligands, and (iii) optimize sub-cellular localization of the drug. This chapter describes the techniques successfully employed for the preparation of polymer nanocarriers (PNC) loaded with the antioxidant enzyme, catalase, and targeted to endothelial cells. Methods of PNC synthesis, loading with catalase, characterization, coupling of a targeting moiety, and in vitro testing of the enzymatic and targeting activities are provided here. Advantages and disadvantages of specific designs are discussed. Due to the modular nature of the targeting methodology employed, it is believed that these protocols will provide a solid foundation for the formulation of a wide variety of enzymatic drug targeting strategies.
authors.affiliation: Vertex Pharmaceuticals, Inc, Formulation Development, 130 Waverly Street, Cambridge, MA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Simone
authors.forename: Thomas
authors.initials: T
authors.lastname: Dziubla
authors.forename: Vladimir
authors.initials: V
authors.lastname: Shuvaev
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykantov
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D049329:Nanostructures / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D004337:Drug Carriers; D011108:Polymers; D002374:Catalase