Biomacromolecules as carriers in drug delivery and tissue engineering

Abstract

Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.

Keywords: ABD, albumin binding domain; ACM, aclacinomycin; ACS, absorbable collagen sponge; ADH, adipic dihydrazide; ART, artemisinin; ASF, Antheraea mylitta silk fibroin; ATRA, all-trans retinoic acid; ATS, artesunate; BCEC, brain capillary endothelial cells; BMP-2, bone morphogenetic protein-2; BSA, bovine serum albumin; BSF, Bombyx mori silk fibroin; Biomacromolecule; CC-HAM, core-crosslinked polymeric micelle based hyaluronic acid; CD, cyclodextrin; CD-NPs, amphiphilic MMA–tBA β-CD star copolymers that are capable of forming nanoparticles; CD-g-CS, chitosan grafted with β-cyclodextrin; CD/BP, cyclodextrin–bisphosphonate complexes; CIA, collagen-induced arthritis; CM, collagen matrices; CMD-ChNP, carboxylmethyl dextran chitosan nanoparticle; DHA, dihydroartesunate; DOXO-EMCH, (6-maleimidocaproyl)hydrazone derivative of doxorubicin; DOX–TRF, doxorubincin–transferrin conjugate; DTX-HPLGA, HA coated PLGA nanoparticulate docetaxel; Drug delivery; ECM, extracellular matrix; EMT, epithelial mesenchymal transition; EPR, enhanced permeability and retention; FcRn, neonatal Fc receptor; GAG, glycosaminoglycan; GC-DOX, glycol–chitosan–doxorubicin conjugate; GDNF, glial-derived neurotrophic factor; GO, grapheme oxide; GSH, glutathione; Gd, gadolinium; HA, hyaluronic acid; HA-CA, catechol-modified hyaluronic acid; HCF, heparin-conjugated fibrin; HDL, high density lipoprotein; HEK, human embryonic kidney; HSA, human serum albumin; IDL, intermediate density lipoprotein; INF, interferon; LDL, low density lipoprotein; LDLR, low density lipoprotein receptor; LDV, leucine–aspartic acid–valine; LMWH, low molecular weight heparin; MSA, mouse serum albumin; MTX–HSA, methotrexate–albumin conjugate; NIR, near-infrared; NSCLC, non-small cell lung cancer; OP-Gel-NS, oxidized pectin-gelatin-nanosliver; PEC, polyelectrolyte; PTX, paclitaxel; Polysaccharide; Protein; RES, reticuloendothelial system; RGD, Arg–Gly–Asp peptide; SF, silk fibroin; SF-CSNP, silk fibroin modified chitosan nanoparticle; SFNP, silk fibroin nanoparticle; SPARC, secreted protein acidic and rich in cysteine; TRAIL, tumor-necrosis factor-related apoptosis-inducing ligand; Tf, transferrin; TfR, transferrin receptor; Tissue engineering; VEGF, vascular endothelial growth factor; VLDL, very low density lipoprotein; pDNA, plasmid DNA; rHDL, recombinant HDL; rhEGF-2/HA, recombinant human fibroblast growth factor type 2 in a hyaluronic acid carrier.

Graphical abstract

Figure 1

The properties and applications of biomacromolecule-based carriers and structures of representative proteins and polysaccharides.

Figure 2

Schematic illustration of the in vivo process of ABD-based indirect targeting of FcRn in tumor tissues.

Figure 3

Schematic illustration of HA-modified nanoparticles or micelles targeting CD44-overexpressing cancer cells.