Self-Encapsulation of Biomacromolecule Drugs in Porous Microscaffolds with Aqueous Two-Phase Systems.

Jian Kang,Ziwei Wu,Wei-En Yuan,Yunpeng Cai,Siyi Wang

doi:10.3390/pharmaceutics13030426

Abstract

At present, the most commonly used methods of microencapsulation of protein drugs such as spray drying, multiple emulsification, and phase separation, can easily cause the problem of protein instability, which leads to low bioavailability and uncontrolled release of protein drugs. Herein, a novel method to encapsulate protein drugs into porous microscaffolds effectively and stably was described. Ammonium hydrogen carbonate (NH4HCO3) was employed to prepare porous microscaffolds. α-Amylase was encapsulated into the porous microscaffolds without denaturing conditions by an aqueous two-phase system (PEG/Sulfate). The pores were closed by heating above the glass transition temperature to achieve a sustained release of microscaffolds. The pore-closed microscaffolds were characterized and released in vitro. The integrity and activity of protein drugs were investigated to verify that this method was friendly to protein drugs. Results showed that the pores were successfully closed and a high loading amount of 9.67 ± 6.28% (w/w) was achieved. The pore-closed microscaffolds released more than two weeks without initial burst, and a high relative activity (92% compared with native one) of protein demonstrated the feasibility of this method for protein drug encapsulation and delivery.

Highlights

Biodegradable polymeric microparticles/microscaffolds mainly based on poly (D, L-lactic-co-glycolic acid) (PLGA) have been extensively studied as an injectable sustained release depot for protein delivery over the decades [1]
Aqueous two-phase systems were investigated to decide what kind of protein drugs have the potential to be partitioned into the porous microscaffolds
The uncertainty of salt concentration made it difficult to determine the actual protein drug concentration in the poly(ethylene glycol) (PEG) phase, even when the standard curve was corrected with the corresponding salt

Summary

Introduction

Biodegradable polymeric microparticles/microscaffolds mainly based on poly (D, L-lactic-co-glycolic acid) (PLGA) have been extensively studied as an injectable sustained release depot for protein delivery over the decades [1]. Protein instability leads to low bioavailability and uncontrolled release of protein drugs loaded microparticles/microscaffolds, which makes protein stability an urgent problem. To address the stability issue, some researchers have turned to porous microparticles/microscaffolds, which have a high capacity for protein loading due to its porous structure [5]. M. et al found that high protein loading efficiencies were achieved in porous microspheres. Protein is encapsulated into porous microparticles/microscaffolds to avoid the problems caused by traditional preparation methods. After the protein is loaded, the pores of the particles are closed to form a sustained release depot

Methods

Results

Conclusion