title: Sheddable coatings for long-circulating nanoparticles.
abstract: Nanoparticles, such as liposomes, polymeric micelles, lipoplexes and polyplexes are frequently studied as targeted drug carrier systems. The ability of these particles to circulate in the bloodstream for a prolonged period of time is often a prerequisite for successful targeted delivery. To achieve this, hydrophilic 'stealth' polymers, such as poly(ethylene glycol) (PEG), are used as coating materials. Such polymers shield the particle surface and thereby reduce opsonization by blood proteins and uptake by macrophages of the mononuclear phagocyte system. Yet, after localizing in the pathological site, nanoparticles should deliver their contents in an efficient manner to achieve a sufficient therapeutic response. The polymer coating, however, may hinder drug release and target cell interaction and can therefore be an obstacle in the realization of the therapeutic response. Attempts have been made to enhance the therapeutic efficacy of sterically stabilized nanoparticles by means of shedding, i.e. a loss of the coating after arrival at the target site. Such an 'unmasking' process may facilitate drug release and/or target cell interaction processes. This review presents an overview of the literature regarding different shedding strategies that have been investigated for the preparation of sterically stabilized nanoparticulates. Detach mechanisms and stimuli that have been used are described.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Sorbonnelaan 16, Utrecht, The Netherlands.
authors.forename: Birgit
authors.initials: B
authors.lastname: Romberg
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016503:Drug Delivery Systems; D005079:Excipients; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
chemical_list: D005079:Excipients; D007202:Indicators and Reagents; D010455:Peptides; D011108:Polymers; D011092:Polyethylene Glycols