Long-circulating poly(ethylene glycol)-coated poly(lactid-co-glycolid) microcapsules as potential carriers for intravenously administered drugs

Abstract

The intrinsic advantages of microcapsules with regard to nanocapsules as intravenous drug carrier systems are still not fully exploited. Especially, in clinical situations where a long-term drug release within the vascular system is desired, if large amounts of drug have to be administered or if capillary leakage occurs, long-circulating microparticles may display a superior alternative to nanoparticles. Here, microcapsules were synthesised and parameters such as in vitro tendency of agglomeration, protein adsorption and in vivo performance were investigated. Biocompatible poly(ethylene glycol) (PEG)-coated poly(DL-lactide-co-glycolide) (PLGA) as wall material, solid and perfluorodecalin (PFD)-filled PEG-PLGA microcapsules (1.5 µm diameter) were manufactured by using a modified solvent evaporation method with either 1% poly(vinyl alcohol) (PVA) or 1.5% cholate as emulsifying agents. Compared to microcapsules manufactured with cholate, the protein adsorption (albumin and IgG) was clearly decreased and agglomeration of capsules was prevented, when PVA was used. The intravenous administration of these microcapsules, both solid and PFD-filled, in rats was successful and exhibited a circulatory half-life of about 1 h. Our data clearly demonstrate that PEG-PLGA microcapsules, manufactured by using PVA, are suitable biocompatible, long-circulating drug carriers, applicable for intravenous administration.

Oxygen delivery using engineered microparticles

“…We developed a two-stage, emulsion-based approach that uses a phase separation step to generate core-shell particles followed by a spontaneous selfemulsification step that results in the formation of an interconnected porous network within the shell structure. PLGA was chosen as the shell material because of its documented use in the medical device and pharmaceutical industry and for its ability to form core-shell structures using phase separation (24,25). To manufacture PHMs, PLGA (shell material), perfluorooctyl bromide (nonsolvent) (PFOB) and Pluronic F-68 (self-emulsifying agent) were dissolved in dicholoromethane (common solvent) (DCM) and emulsified in an aqueous solution [0.5 wt% polyvinylppyrrolidone (PVP)] to produce an oil-in-water emulsion (Fig.…”

Perfluorocarbon-based oxygen carriers: from physics to physiology

“…There are three ways to reduce this process: Firstly, through choosing the adequate emulsifiers such as endogenous proteins and lipids. Secondly, via the attachment of polyethylene glycol (so-called PEGylation) to the outside of the particle, which sterically hinders the general interaction of proteins with the droplet surface [ 25 , 35 , 52 ]. Thirdly, by carefully adjusting the droplet size, which influences the circulation of PFC droplets in the blood.…”

Safety of poly (ethylene glycol)-coated perfluorodecalin-filled poly (lactide-co-glycolide) microcapsules following intravenous administration of high amounts in rats

“…However, typical problems such as biological incompatibility of the used emulsifiers, coalescence and flocculation of emulsion droplets leading to an increased particle size could not be satisfactorily eliminated [ 3 ]. We tried to overcome these problems by engineering biocompatible poly (ethylene glycol)-coated poly ( d , l -lactide-co-glycolide) microcapsules (PLGA microcapsules) with a PFC core [ 4 , 5 ]. PLGA and poly (ethylene glycol) (PEG) are metabolizable, harmless compounds, that are approved by the Food and Drug Administration for internal use in humans, thus representing ideal raw materials for the design of intravenously applicable drug carriers [ 5 ].…”