Nanoparticles for Therapeutic Cargos — Protein Drugs

Most of proteins are potent and specific in their physiological activities and have become drugs of choice for the treatment of numerous diseases as a result of their striking selectivity and their ability to provide effective and potent action on disease treatment. Major issues in protein drug delivery include the stabilization of proteins in delivery devices and the design of appropriate protein carriers. CD Bioparticles is experienced in offering custom products and services to deliver your protein drugs by appropriate and effective nanocarriers.

Protein Drugs Introduction

Protein drugs represent an irreplaceable part of the pharmaceuticals coming on the market every year and are now widely applied to treat or relieve symptoms related to many metabolic and oncologic diseases. Most proteins cannot be delivered orally due to their degradation in the acidic environment of the gastrointestinal tract. Protein drugs are commonly administrated by intravenous injections, which are usually not well tolerated by the recipient. In addition, the transportation of protein drugs in the body is limited by their high molecular weight, which prevents the crossing of tissue barriers, and by their short lifetime due to immune response and enzymatic degradation. However, the short half-lives and wide tissue distribution of protein drugs in the blood stream lead to frequent and high doses of drugs in order to obtain therapeutic efficacy. Systemic administration in high doses can lead to side effects and can also be toxic. Also, physiochemical properties like fragile molecules, complex structure, protein denaturation, and change in spatial characteristics as well as potential for immunogenicity limited the development of proteins drugs as therapeutic agents. Thus, advanced drug delivery strategy - nanocarriers show great superiority in maintaining structure and activity of protein drugs during preparation and delivery as well as during shipping and long-term storage.

Nanocarriers allow for the encapsulation of proteins inside a matrix of great biocompatibility, thus protecting them against hydrolysis and enzymatic degradation. They can be designed to control the dispatch of the loaded drug to different areas, increasing its local concentration and therapeutic efficiency, while prolonging its retention, half-life, and effectiveness. They can also avoid diffusion of the protein drugs into normal organs, thus avoiding negative side effects. Moreover, nanocarriers can be targeted to certain sites based on particle size, surface charge, surface modification, and hydrophobicity.

Carriers such as biodegradable polymeric nanoparticles (poly-lactic acid, poly (lactic-co-glycolic acid), polycaprolactone), chitosan nanoparticles and solid lipid nanoparticles, as well as liposomes, have shown great potential in the delivery of proteins drugs. Many well-established nanocarrier systems have been developed for controllable delivery of protein drugs.

Application of Nanoparticles in Protein Drug Delivery

With the deepening of nanoparticle research, there are more and more explorations in the field of protein drug delivery. Among them, the more popular delivery ingredients include: peptide, protein, growth factor, enzymes, antibody, and ADC drugs.

Peptide drugs: Scientists have investigated the incorporation of nanoparticles in peptide-based drugs to improve their stability, bioavailability, and targeted delivery. For example，in a study published in the journal Biomaterials, researchers developed lipid-based nanoparticles to encapsulate a therapeutic peptide for the treatment of diabetes. The nanoparticles protected the peptide from degradation and allowed for sustained release, resulting in improved therapeutic outcomes.

Protein drugs: In the field of protein therapeutics, nanoparticles have been explored as carriers to protect and deliver proteins to specific sites in the body. Studies have examined the use of nanoparticle platforms, such as liposomes or polymer-based nanoparticles, to encapsulate and stabilize protein drugs, prolonging their circulation time and minimizing degradation. For example，scientists at MIT developed a nanoparticle platform for the delivery of protein-based drugs, as reported in the journal Nature Biotechnology. They designed a self-assembling nanoparticle system that encapsulated therapeutic proteins, such as insulin or erythropoietin, protecting them from enzymatic degradation and extending their circulation time in the body.

Growth factor drugs: Nanoparticles have been investigated for their potential to enhance the delivery and efficacy of growth factor-based therapies. Researchers have explored surface modification of nanoparticles to enable controlled release of growth factors, improving their bioavailability and promoting tissue regeneration in various biomedical applications, such as wound healing or bone repair. For example, in a study published in ACS Nano, researchers engineered gold nanoparticles loaded with vascular endothelial growth factor (VEGF) for the promotion of blood vessel formation. The nanoparticles provided controlled release of VEGF, enhancing its stability and bioavailability, and facilitated targeted delivery to damaged tissues for improved tissue regeneration.

Enzyme drugs: The use of nanoparticles as carriers for enzyme-based drugs has shown promise in enhancing their stability and targeted delivery. Researchers have explored approaches such as encapsulating enzymes within nanoparticle matrices or attaching them onto nanoparticle surfaces, allowing for controlled release and protection against degradation. A research team reported in the journal Advanced Materials on the development of mesoporous silica nanoparticles for the delivery of enzyme therapeutics. They loaded the nanoparticles with catalase, an antioxidant enzyme, and demonstrated its protection against degradation and improved therapeutic efficacy in a model of oxidative stress-induced tissue injury.

Antibody drugs: Nanoparticles have been explored as platforms for antibody-based therapeutics, aiming to improve their pharmacokinetics and targeting capabilities. Researchers have investigated the conjugation of antibodies onto nanoparticle surfaces, enabling selective delivery to specific cells or tissues, and enhancing antibody stability and circulation time in the body.In a study published in Science Translational Medicine, scientists utilized polymeric nanoparticles coated with antibodies for targeted delivery of anticancer drugs. The nanoparticles were functionalized with antibodies specific to cancer cell surface markers, enabling selective binding and internalization of the nanoparticles, thereby enhancing drug delivery and minimizing off-target effects.

Antibody-drug conjugates (ADCs): ADCs combine the specificity of antibodies with the cytotoxicity of small molecule drugs. Researchers have explored nanoparticle-based systems for ADC delivery, allowing for the targeted release of the cytotoxic payload at the tumor site while minimizing off-target effects. Nanoparticles have been investigated as carriers for ADCs to enhance their stability, controlled release, and tumor penetration. Researchers reported in the journal Nature Communications on the development of hybrid nanoparticles for the delivery of ADCs. They encapsulated a potent cytotoxic drug within a nanoparticle core and decorated the surface with targeting antibodies. This nanoparticle-based ADC system exhibited improved tumor targeting, enhanced internalization, and increased efficacy in preclinical models of cancer.

Figure 1. Proteins were encapsulated in a nanosized matrix prepared with monomers and a bisacrylated peptide cross-linker which can be specifically recognized and cleaved by furin and then release encapsulated cargos. In this research, protein cargos of different sizes and tertiary structures can be encapsulated and released reversibly without loss of bioactivity. (Biswas, A., et al. ACS nano, 2011, 5(2), 1385-1394.)

Our Featured Services

CD Bioparticles is specialized in the development of drug delivery systems and customizing nanoparticles for protein drug delivery utilizing our core technologies. With our high-quality products and services, the efficacy of your protein drug delivery can be tremendously improved.

We offer well-designed protein drug (native proteins, recombinant proteins, and others) production together with its loaded products in biodegradable polymer, chitosan and lipid matrix. We are experienced in providing protein drugs and can also help you choose appropriate carriers for protein drugs given. Carrier properties such as molecular weight, surface charges and charge density, solubility, and hydrophobicity could be designed and engineered at your will; as well as the addition of desired chemical groups or targeting moieties for further functionalization.

References:
1. Dai, C., Wang, B., Zhao, H. Microencapsulation peptide and protein drugs delivery system. Colloids and Surfaces B: Biointerfaces, 2005, 41(2-3), 117-120.
2. Jain, A., Jain, A., Gulbake, A., Shilpi, S., Hurkat, P., Jain, S. K. Peptide and protein delivery using new drug delivery systems. Critical Reviews™ in Therapeutic Drug Carrier Systems, 2013, 30(4).
3. Bruno, B. J., Miller, G. D., Lim, C. S. Basics and recent advances in peptide and protein drug delivery. Therapeutic delivery, 2013, 4(11), 1443-1467.
4. Solaro, R., Chiellini, F., Battisti, A. Targeted delivery of protein drugs by nanocarriers. Materials, 2010, 3(3), 1928-1980.