# Diversity of Collagen Proteins and Their Biomedical Applications in Drug Delivery
## 4 Collagen Application for Drug Delivery
### Delivery of Small Molecule Drug  
Collagen has a stable triple-helix structure that can form a natural network structure. These structures can realize the effective loading and slow release of small molecule drugs, which is an ideal material for drug delivery. As shown in Figure 4, the collagen hydrogel was developed to deliver tetrahydrocurcumin (THC) [92]. The nanoparticles were prepared to carry doxorubicin hydrochloride (DOX) [93]. A chitosan-collagen film was made to release local anesthetics (LA) [94]. A scaffold made of type I collagen was used to alendronate (Aln) [95]. THC is obtained by hydrogenating curcumin and has a significant impact on the pharmaceutical and cosmetic industries. However, THC possesses low solubility in water, poor absorption, and rapid elimination in the body. To improve these disadvantages of THC, a novel hydrogel was prepared with porcine skin collagen using 3D printing technique to treat wound healing [92]. In cancer chemotherapy, DOX is a well-known anticancer agent. To realize the targeted and controlled release of DOX, the nanoparticles based on chitosan and collagen peptide (CP) were prepared, which are stable under physiological conditions and have the capability of pH-controlled release. The formation of CPCN nanoparticles is attributed to hydrogen bonding and electrostatic interactions. The results of the anticancer test showed that DOX-loaded NPs have significant anti-proliferative characteristics against HeLa cells [93]. LAs are commonly utilized in clinical settings to alleviate both acute and chronic pain. Prolonging LAs remains a difficult task. A research group has initiated the development of a chitosan-collagen film for a controlled delivery of combinations of local anesthetics, including lidocaine, benzocaine, and tetracaine. The film was composed of low molecular weight chitosan and calf skin collagen and could hold and release a mixture of the local anesthetics in a proper ratio within 24 h [94]. Aln, a second-generation bisphosphonate, is well-known as an anti-osteoporosis drug based on its dual functions of restraining osteoclasts and stimulating osteoblasts. It is an engineered implantable scaffold based on type I collagen that can sustainably release Aln to repair osteoporotic bone defects and resist bone loss in osteoporosis. The release kinetics showed that Aln was released at an average rate of 2.99 \(\mu\)g/d in the initial 8 days and could sustainably be released for 1 month [95]. Silymarin, a bioactive compound extracted from plant milk thistle, has been widely regarded as an effective treatment for liver diseases such as alcoholic fatty liver and viral hepatitis. In addition, it possesses the properties of neuroprotection, antioxidant, and tissue regeneration. Herein, the micellar nanoparticles based on ovine collagen were prepared and applied to deliver silymarin to treat ischemic brain injury. The animal test demonstrated that nanosilymarin had a marked improvement in neuroprotection when compared to the silymarin-treated control [96]. Vancomycin, belonging to the glycopeptide antibiotic family, is used to treat a variety of infections caused by pathogenic bacteria. A system for delivering antibiotics has been created, combining elastin-like peptide and collagen-like peptide nanovesicles (ECnVs) to fight pathogenic bacteria such as Staphylococcus aureus (MRSA). Chemical synthesis was used to create collagen-like peptide in this study. This delivery system exploited the synergy effects of peptide nanocarriers and their interactions with collagen-based scaffolds [97]. To reduce the infectious risk caused by the guided bone regeneration (GBR) material, a composite restoration material made of oxidized hyaluronic acid (HA)/type I collagen integrated with tricalcium phosphate (\(\beta\)-TCP) was applied to cure bone regeneration. The composite had a prominent mechanical strength and biocompatibility and guided the sustainable release of tetracycline for 5 days [98].