Biocompatible and Biodegradable Polymersome Encapsulated Hemoglobin: A Potential Oxygen Carrier

Abstract

This work describes the development of polymersome-encapsulated hemoglobin (PEH) self-assembled from biodegradable and biocompatible amphiphilic diblock copolymers composed of poly(ethylene oxide) (PEO), poly(caprolactone) (PCL), and poly(lactide) (PLA). In the amphiphilic diblock, PEO functions as the hydrophilic block, while either PCL or PLA can function as the hydrophobic block. PEO, PCL, and PLA are biocompatible polymers, while the last two polymers are biodegradable. PEH dispersions were prepared by extrusion through 100 nm pore radii polycarbonate membranes. In this work, the encapsulation efficiency of human and bovine hemoglobin (hHb and bHb) in polymersomes was adjusted by varying the initial concentration of Hb. This approach yielded Hb loading capacities that were comparable to values in the literature that supported the successful resuscitation of hamsters experiencing hemorrhagic shock. Moreover, the Hb loading capacities of PEHs in this study can also be tailored simply by controlling the diblock copolymer concentration. In this study, typical Hb/diblock copolymer weight ratios ranged 1.2-1.5, with initial Hb concentrations less than 100 mg/mL. The size distribution, Hb encapsulation efficiency, oxygen affinity (P 50), cooperativity coefficient (n), and methemoglobin (metHb) level of these novel PEH dispersions were consistent with values required for efficient oxygen delivery in the systemic circulation. Taken together, our results demonstrate the development of novel PEH dispersions that are both biocompatible and biodegradable. These novel dispersions show very good promise as therapeutic oxygen carriers.

SOD Antioxidant Nanoreactors: Influence of Block Copolymer Composition on the Nanoreactor Efficiency

“…The thickness of the vesicles membrane depended on the weight of the hydrophobic block, as has been reported for other amphiphilic block copolymers. [28] Based on previous reports concerning PMOXA-PDMS-PMOXA block copolymers [32] we have estimated for ABA3 a thickness of around 24 nm; combined with the intermediate size of the vesicles (radius 167 nm), this led us to assume that the inner available space for encapsulation is comparable to that of ABA2 vesicles (Table 2). Vesicles containing the enzyme were stable for more than one month at 5 8C, and did not change their hydrodynamic radius, as previously reported.…”

“…[27,28] The relation between the size of the block copolymers and the vesicles was attributed by Eisenberg to the size of the hydrophilic block and the overall thickness of the membrane in the case of polystyrene-poly(acrylic acid) (PS-PAA) diblock copolymers, while Discher indicated that the thickness of the vesicle wall is proportional with the length of the hydrophobic block. [27,28] However, the nanoreactors already reported were introduced only as a concept, [1,2,[8][9][10] without further modulation of their properties to gain insight into their role or to optimize their function. The aim of our study is to compare nanoreactors made of three PMOXA-PDMS-PMOXA block copolymers in terms of vesicle size, encapsulation efficiency and superoxide radical anions permeability.…”

Self‐Assembled Block Copolymer Aggregates: From Micelles to Vesicles and their Biological Applications

“…[125] Therapeutic oxygen carriers based on PEO-PCL or PEO-PLA copolymer vesicles that are successfully loaded with either human or bovine haemoglobin that exhibits good oxygen binding and release, have been developed for potential applications as haemoglobinbased oxygen carriers for the treatment of ischemic tissues. [126] Membrane Loading of Polymer Vesicles for Medical Uses…”

A Three‐Enzyme Cascade Reaction through Positional Assembly of Enzymes in a Polymersome Nanoreactor

“…Rameez et al determined the efficiency of haemoglobin (Hb) encapsulation in the polymersome lumen by lysis of the vesicles, followed by UV/Vis detection of released Hb with an Hb-specific protocol. [28] For a more general approach, we chose to employ a commercially available ruthenium complex with an isothiocyanato moiety (3), which is easily covalently linked to any molecules containing free amines, as most proteins do in their lysine residues or N termini. After encapsulation or immobilisation, the use of inductively coupled plasma-mass spectrometry (ICP-MS), allowed the quantitative detection of ruthenium, and hence, of proteins.…”