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

Abstract

The host response against foreign materials designates the biocompatibility of intravenously administered microcapsules and thus, widely affects their potential for subsequent clinical use as artificial oxygen/drug carriers. Therefore, body distribution and systemic parameters, as well as markers of inflammation and indicators of organ damage were carefully evaluated after administration of short-chained poly (vinyl alcohol, (PVA)) solution or poly (ethylene glycol (PEG))-shielded perfluorodecalin-filled poly (d,l-lactide-co-glycolide, PFD-filled PLGA) microcapsules into Wistar rats. Whereas PVA infusion was well tolerated, all animals survived the selected dose of 1247 mg microcapsules/kg body weight but showed marked toxicity (increased enzyme activities, rising pro-inflammatory cytokines and complement factors) and developed a mild metabolic acidosis. The observed hypotension emerging immediately after start of capsule infusion was transient and mean arterial blood pressure restored to baseline within 70 min. Microcapsules accumulated in spleen and liver (but not in other organs) and partly occluded hepatic microcirculation reducing sinusoidal perfusion rate by about 20%.Intravenous infusion of high amounts of PFD-filled PLGA microcapsules was tolerated temporarily but associated with severe side effects such as hypotension and organ damage. Short-chained PVA displays excellent biocompatibility and thus, can be utilized as emulsifier for the preparation of drug carriers designed for intravenous use.

Perfluorocarbon-based oxygen carriers: from physics to physiology

“…When the first Food and Drug Administration (FDA)–approved PFC emulsions such as Fluosol-DA and Perftoran came up in the 1980s, they suffered from flocculation, which gave the products weak shelf life [ 81 ]. The used emulsifiers were block polymers sometimes mixed with lecithin or phospholipids, which generate too little surface charge density to prevent this process [ 24 ]. Freezing the emulsion prior to storage was insufficient because of decay during thawing, which made it necessary to sonicate the emulsion prior to use.…”

Overcoming challenges in treating autoimmuntity: Development of tolerogenic immune-modifying nanoparticles

“…In one study, poly(ethylene glycol)-poly(lactide- co -glycolide) (PEG-PLGA) microcapsules (1.5 μm in diameter) that encapsulated perfluorodecalin (PFD) were intravenously administered to Wistar rats at a dose of 1247 mg/kg (i.e., 202 mg/kg, human equivalent dose; HED). 41 The purpose of this study was to evaluate PFD-filled PEG-PLGA microcapsules as artificial oxygen/drug carriers. Microcapsules were administered by syringe pump (30 min, 20 mL/kg body weight × hour).…”

Effect of Stratification on Surface Properties of Corneal Epithelial Cells

“…The choice of perfluorocarbons was based on their insolubility in aqueous solutions, their nontoxicity, their inertness, and their precedent usage for biomedical applications. [18][19][20] The air bubbles or perfluorocarbon droplets (10 lL) were placed in contact with the cellular surface. The stage was tilted at a rate of 0.58/s, and the advancing and receding angle values were measured every second until the bubble/droplet rolled off the surface.…”