title: Carboxylesterase-triggered hydrolysis of nanoparticle PEGylating agents.
abstract: Despite the importance of PEGylation in achieving long nanoparticle circulation times, many nanoparticles are coated with PEGylating agents susceptible to enzymatic degradation. In this study, solid lipid nanoparticles (SLNs) prepared with ester-containing compounds were evaluated for their stability in the presence of carboxylesterase. SLN suspensions became turbid within 30 min of enzymatic exposure, indicating possible disassociation of a portion of the nanoparticles. The particle size of SLNs incubated with the enzyme was smaller than the size of controls, although their morphologies appeared similar in transmission electron microscopy images. Although SLNs offered some protection over micelles, PEG6000 monostearate was rapidly degraded within 15 min. Hydrolysis of polysorbate 60 was much slower, reaching only 36% in 2 h. These studies reveal the importance of confirming the stability of PEG surface coatings prior to undertaking in vivo experiments in small animal models, which can have considerably higher plasma esterase activity than humans.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0596, United States.
authors: Melissa D
authors: MD
authors: Howard
authors: Xiuling
authors: X
authors: Lu
authors: John J
authors: JJ
authors: Rinehart
authors: Michael
authors: M
authors: Jay
authors: Thomas D
authors: TD
authors: Dziubla
mesh_terms: D000818:Animals; D043182:Carboxylesterase / Q000378:metabolism*; D004355:Drug Stability; D005230:Fatty Acids, Nonesterified / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013499:Surface Properties; D013552:Swine
chemical_list: D005230:Fatty Acids, Nonesterified; D011092:Polyethylene Glycols; D043182:Carboxylesterase