Poly(2-ethyl-2-oxazoline)-Conjugated Porcine Serum Albumin as a Veterinary Albumin Therapeutic

Advances in veterinary medicine have greatly improved the health and quality of life of companion animals. However, no reliable supply system exists for blood-derived products. Poly(2-ethyl-2-oxazoline)-conjugated porcine serum albumin (POx-PSA) was engineered as a veterinary albumin therapeutic to maintain circulating blood volume in domestic cats and dogs. This study details the synthesis, structural characteristics, and physicochemical properties of POx_M-n-PSA conjugates bearing varying average numbers (n) of POx_M chains (where M denotes polymer molecular weight). Their preclinical safety, efficacy, and non-toxicity were further assessed in vivo. The conjugation number n was precisely controlled within the range of 1-17. Four variants-POx_5k-6-PSA, POx_5k-10-PSA, POx_10k-6-PSA, and POx_10k-10-PSA-were prepared, and their solution properties were comprehensively analyzed. Particle size increased proportionally with POx chain length. At equivalent PSA concentrations, both viscosity and colloid osmotic pressure increased with higher POx molecular weight and greater degrees of conjugation. Among the prepared conjugates, POx_5k-6-PSA was identified as the most suitable structure for veterinary albumin therapeutic. In a rat hemorrhagic shock model, POx_5k-6-PSA rapidly restored mean arterial pressure and the heart rate to pre-shock levels. No abnormalities were observed in serum biochemical parameters or histopathological examinations at 2 h or 7 days post-resuscitation. Moreover, rats receiving a high dose corresponding to 2.4-fold the anticipated maximum clinical dose exhibited no adverse clinical signs or organ alternations over a 14-day monitoring period. These findings demonstrate that POx_5k-6-PSA effectively replenishes circulating blood volume and exhibits a favorable safety and efficacy as a veterinary albumin therapeutic.