Protein-Based Nanoparticles as Drug Delivery Systems

Abstract

Nanoparticles have been extensively used as carriers for the delivery of chemicals and biomolecular drugs, such as anticancer drugs and therapeutic proteins. Natural biomolecules, such as proteins, are an attractive alternative to synthetic polymers commonly used in nanoparticle formulation because of their safety. In general, protein nanoparticles offer many advantages, such as biocompatibility and biodegradability. Moreover, the preparation of protein nanoparticles and the corresponding encapsulation process involved mild conditions without the use of toxic chemicals or organic solvents. Protein nanoparticles can be generated using proteins, such as fibroins, albumin, gelatin, gliadine, legumin, 30Kc19, lipoprotein, and ferritin proteins, and are prepared through emulsion, electrospray, and desolvation methods. This review introduces the proteins used and methods used in generating protein nanoparticles and compares the corresponding advantages and disadvantages of each.

Keywords: biocompatible; biodegradable; controlled release; drug delivery; protein nanoparticle.

Figure 1

Delivery of protein nanoparticle to the cell. Intracellular delivery of insoluble drugs by protein nanoparticles via the endocytosis process. Protein nanoparticles have several advantages as a drug delivery system, such as increased stability and activity due to increased protection from enzymatic degradation, immunogenicity, phagocytosis, and renal clearance, thereby leading an increase in the half-life of the drug.

Figure 2

Categorization of methods for preparing protein nanoparticles. (a) The chemical method produces protein nanoparticles using a chemical reaction and includes emulsion and complex coacervation. (b) The physical method includes physically aggregating after separating proteins into nanosized particles and includes an electrospray technique and a nano spray drying method. (c) The self-assembly method is a method of making nanoparticles by agglutinating proteins by themselves and it includes the desolvation method.

Figure 3

(a) The emulsion process is a method of forming nanoparticles by removing solvent/non-solvent after an emulsion system is formed by dispersing via mechanical agitation or ultrasonic waves. Moreover, a double emulsion method was also used. (b) The complex coacervation method adjusts the pH to producing the protein cationic or anionic and then interacts with other polymers to produce nanoparticles.

Figure 4

(a) Nano spray drying is the process of releasing and drying a protein liquid jet stream with a nozzle using heated nitrogen and carbon dioxide gas to produce nanoparticles. (b) The electrospray technique generates nanoparticles by ejecting a liquid jet stream through a nozzle that forms an aerosolized droplet by applying a high voltage to a protein solution supplied through a nebulizer.

Figure 5

(a) In the self-assembly method, individual protein chains are dissolved in an aqueous solution and a CMT exceeding the CMC to spontaneously generate protein micelles during the formation of nanosized aggregates. (b) In the desolvation method, nanoparticles are prepared through a simple process of adding a desolvating agent to a protein solution containing drugs.