Polymersome Encapsulated Hemoglobin:  A Novel Type of Oxygen Carrier

Abstract

Bovine hemoglobin (Hb) was encapsulated inside polymer vesicles (polymersomes) to form polymersome encapsulated Hb (PEH) dispersions. PEH particles are 100% surface PEGylated with longer PEG chains and possess thicker hydrophobic membranes as compared to conventional liposomes. Polymersomes were self-assembled from poly(butadiene)-poly(ethylene glycol) (PBD-PEO) amphiphilic diblock copolymers with PBD-PEO molecular weights of 22-12.6, 5-2.3, 2.5-1.3, and 1.8-0.9 kDa. The first two diblock copolymers possessed linear hydrophobic PBD blocks, while the later possessed branched PBD blocks. PEH dispersions were extruded through 100 and 200 nm pore radii membranes. The size distribution, Hb encapsulation efficiency, P(50), cooperativity coefficient, and methemoglobin (metHb) level of PEH dispersions were consistent with values required for efficient oxygen delivery in the systemic circulation. The influence of different molecular weight diblock copolymers on the physical properties of PEH dispersions was analyzed. PBD-PEO copolymers with molecular weights of 22-12.6 and 2.5-1.3 kDa completely dissolved in aqueous solution to form polymersomes, while the other two copolymers formed a mixture of solid copolymer precipitates and polymersomes. PEHs self-assembled from 22-12.6 and 2.5-1.3 kDa PBD-PEO copolymers possessed Hb loading capacities greater than PEG-LEHs, PEGylated actin-containing LEHs, and nonmodified LEHs, although their sizes were smaller and their hydrophobic membranes were thicker. The Hb loading capacities of these polymersomes were also higher than lipogel encapsulated hemoglobin particles and nanoscale hydrogel encapsulated hemoglobin particles. PEH dispersions exhibited average radii larger than 50 nm and exhibited oxygen affinities comparable to human erythrocytes. Polymersomes did not induce Hb oxidation. The interaction between Hb and the membrane of 2.5-1.3 kDa PBD-PEO polymersomes improved the monodispersity of these particular PEH dispersions. These results suggest that PEHs could serve as efficient oxygen therapeutics.

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

“…Lee et al successfully encapsulated myoglobin, hemoglobin, and albumin in PEO-b-PBD based polymer vesicles at varying degrees of encapsulation efficiency [5]. Arifin and Palmer further demonstrated that bovine hemoglobin (Hb) could be encapsulated inside PEO-b-PBD polymer vesicles with oxygen affinities similar to those of human red blood cells; they demonstrated that these "polymersomes-encapuslated hemoglobin" (PEH) dispersions could store and transport Hb and potentially act as in vivo oxygen therapeutics [47]. The ability to encapsulate proteins within polymersomes provides a promise for future protein therapies, which are currently facing delivery obstacles.…”

Preparation of ultrapure bovine and human hemoglobin by anion exchange chromatography

“…A variety of HBOCs exist and include: recombinant Hbs [4], cross-linked Hbs [5], polymerized Hbs [6][7][8][9], PEGylated Hbs [10], liposome encapsulated Hbs [11][12][13], polymersome encapsulated Hbs [14] and other particle encapsulated Hbs [15][16][17]. In order to synthesize and/ or formulate these HBOCs, a pure source of Hb is needed.…”

Haemoglobin, oxygen carriers and perioperative organ perfusion

“…A third group, particulate haemoglobin preparations able to carry other useful substances such as enzymes are also studied, but their development is still far from any clinical application [48][49][50][51].…”

“…Unlike liposomes, polymersomes can be completely covered by polyethylene-glycol (PEG). PEG is a biologically inert polymer, used in drug delivery systems and known to be safe for in-vivo administration [48]. It influences the permeability of polymersomes, giving them better mechanical resistance with favourable osmotic properties, thus reducing problems with osmotic pressure gradients.…”