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Review
. 2008 Jan;25(1):55-71.
doi: 10.1007/s11095-007-9348-7. Epub 2007 Jun 6.

Sheddable coatings for long-circulating nanoparticles

Birgit Romberg  1 , Wim E Hennink, Gert Storm
Affiliations
Review

Sheddable coatings for long-circulating nanoparticles

Birgit Romberg et al. Pharm Res. 2008 Jan.

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.

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Figures

Fig. 1
Fig. 1
Schematic representation of the different shedding applications following the localization of sterically stabilized nanoparticles at the target site. Top panel: extracellular shedding leading to: a extracellular release of the entrapped drug and subsequent uptake of the drug, b exposure of a targeting ligand and subsequent receptor-mediated internalization and intracellular drug release and c exposure of a positively charged surface and subsequent internalization and intracellular drug release. Bottom panel: d intracellular shedding after endocytosis and subsequent drug release events.
Fig. 2
Fig. 2
Hydrolysis reactions relevant to acid-sensitive linkers used in sheddable coatings. R1 contains the hydrophilic part of the molecule (PEG), R2 contains the hydrophobic anchor, ODN or PLL, depending on the type of carrier.
Fig. 3
Fig. 3
Reduction-sensitive PEG–S–S–lipid conjugates.
Fig. 4
Fig. 4
Chemical structure of PEG–PE, PEG–Ceramides, PEG–diacylglycerols, PEG–dialkyloxypropylamines and PEG–SAINT.
Fig. 5
Fig. 5
Chemical structure of PHEG–lipid conjugate (n ≈ 20).
See this image and copyright information in PMC

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