A comparison study on the release kinetics and mechanism of bovine serum albumin and nanoencapsulated albumin from hydrogel networks.

An in situ-forming biodegradable hydrogel network has been developed to achieve extended release of protein drugs. Hyaluronic acids (HA) were selected as the scaffolding materials, and modified to afford thiolated HA (HASH) and methacrylated HA (HAME). Under near physiological conditions, a mixture of HASH and HAME achieved efficient sol-gel transition within 10 min at 37 °C. A systematic study was performed to characterize the morphology, rheological properties, swelling, degradation, and biocompatibility of the obtained hydrogel networks. Next, bovine serum albumin (BSA) and its nanocapsules were entrapped in the hydrogel network. Standard in vitro release studies and mathematic modeling were performed to gain insights into the release kinetics and mechanisms of protein drugs from the hydrogel network. For the hydrogel-nanocapsule hybrid system, a mathematical model combining the release processes from nanocapsules and hydrogel networks has been proposed to describe the release behavior of BSA from nanocapsules entrapped in the hydrogel network.

Noncovalent Protein Glycosylation Strategy via In Situ Nanoencapsulation.

An efficient strategy for noncovalent protein glycosylation has been developed by in situ saccharide-based nanoencapsulation. The positive monomer dimethylaminoethyl methacrylate is enriched on the protein surface via electrostatic adhesion, enabling free radical polymerization to generate nanocapsules with saccharides on the surface of the protein complex. Comparable to the glycosylation of native proteins, the d-fructose coated polymeric shell layer significantly enhanced the stability of proteins, rendering proteins with cell selectivity and tumor-specific distribution in MCF-7 breast tumor-bearing mice xenografts. Also, glycosylation improved the shelf life of therapeutic proteins which would further benefit manufacturing and facilitate transportation.

Hierarchical assembly of hyaluronan coated albumin nanoparticles for pancreatic cancer chemoimmunotherapy.

Pancreatic cancer is a highly malignant carcinoma with limited effective treatment options, resulting in a poor patient survival rate of less than 5%. In this study, cationic albumin nanoparticles were assembled with negatively charged hyaluronic acid (HA) to achieve a hierarchical nanostructure and efficient delivery of small molecule drugs to the tumor site in the pancreas. A combination of chemotherapy with indoleamine-2,3-dioxygenase (IDO) inhibition was explored to enhance the chemotherapeutic efficacy in vivo. Hydrophobic celastrol (CLT) and hydrophilic 1-methyltryptophan (MT) were concurrently loaded in HA coated cationic albumin nanoparticles (HNPs) with an average size of ∼300 nm. The size of HNPs was reduced in the presence of hyaluronidase to facilitate penetration into deep tumor tissues. Also, the biodistribution study in the C57BL/6 mice xenograft model showed enhanced tumor accumulation and prolonged circulation of HNPs. Compared with CLT solution, the combination of CLT with MT showed significantly enhanced tumor inhibition in both xenograft and orthotopic pancreatic cancer mice models via downregulating the immunosuppressive tumor microenvironment. Taken together, the combination of CLT with MT administered via HNPs represents a highly promising strategy for targeted pancreatic cancer therapy.