The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles

Abstract

A key attribute for nanoparticles (NPs) that are used in medicine is the ability to avoid rapid uptake by phagocytic cells in the liver and other tissues. Poly(ethylene glycol) (PEG) coatings has been the gold standard in this regard for several decades. Here, we examined hyperbranched polyglycerols (HPG) as an alternate coating on NPs. In earlier work, HPG was modified with amines and subsequently conjugated to poly(lactic acid) (PLA), but that approach compromised the ability of HPG to resist non-specific adsorptions of biomolecules. Instead, we synthesized a copolymer of PLA-HPG by a one-step esterification. NPs were produced from a single emulsion using PLA-HPG: fluorescent dye or the anti-tumor agent camptothecin (CPT) were encapsulated at high efficiency in the NPs. PLA-HPG NPs were quantitatively compared to PLA-PEG NPs, produced using approaches that have been extensively optimized for drug delivery in humans. Despite being similar in size, drug release profile and in vitro cytotoxicity, the PLA-HPG NPs showed significantly longer blood circulation and significantly less liver accumulation than PLA-PEG. CPT-loaded PLA-HPG NPs showed higher stability in suspension and better therapeutic effectiveness against tumors in vivo than CPT-loaded PLA-PEG NPs. Our results suggest that HPG is superior to PEG as a surface coating for NPs in drug delivery.

Intravenous delivery of camptothecin-loaded PLGA nanoparticles for the treatment of intracranial glioma

“…We achieved a loading of CPT in our nanoparticles of $10% by weight; this value is higher than our theoretical loading of 8%, indicating that more PLGA was lost than CPT during the nanoparticle fabrication process. Loss of PLGA during nanoparticle fabrication has been reported previously (Sawyer et al, 2011), and our loading is consistent with the 5-25% loading reported by other groups encapsulating CPT in PLGA (Deng et al, 2014;McCarron et al, 2008). The average hydrated nanoparticle diameter measured by DLS ($200 nm) was larger than the diameter measured by SEM ($120 nm), which is expected, given that NPs will become hydrated in the aqueous environment required for DLS and that a fraction of nanoparticles will experience aggregation after resuspension.…”

“…The method for measuring release of CPT from nanoparticles was adapted from a method described previously (Deng et al, 2014). Nanoparticles (150 mg) with or without CPT were suspended in 2 ml of 1Â PBS and incubated at 37 C on a shaker.…”

Surface zwitterionization of hemocompatible poly(lactic acid) membranes for hemodiafiltration

“…PLA is one of the eco-friendly bioplastics with excellent biodegradability, processibility, less energy dependence and lower cost, which has been widely utilized in biomedical fields such as sutures, resorbable plates and screws, and drug delivery device [12][13][14][15][16]. The Food and Drug Administration (FDA) has also approved PLA for direct contact with biological fluids.…”

Multi‐arm star polymers of lactide obtained in melt in the presence of hyperbranched oligoglycerols

“…33 Polymerization of L-LA in the presence of PG and Sn(Oct) 2 Table 3 (nos. [1][2][3][4][5][6][7][8].…”

“…1,2 They exhibit different physical properties in comparison to their linear homologues, such as lower viscosity in dilute solutions and in the melt, 3 poor mechanical properties and less susceptibility to form crystalline phases. 4 The solubility of HBPs depends mostly on the nature of HBP end groups, degree of branching and solvent.…”