# Collagen Nanoparticles in Drug Delivery Systems and Tissue Engineering
## 3 Collagen-Based NPs in Biomedicine
### Collagen Based NPs in DDS  
[PERSON] et al. aimed at investigating the neuroprotective effect of the silymarin--collagen nanoparticle DDS. They studied the importance of NPs in improving the therapeutic effect of silymarin against neuronal injury. Collagen NPs were fabricated and stabilized using malondialdehydedehyde(MDA) and 3-ethyl carbodiimide-hydrochloride (EDC-HCl) as crosslinking agents. The collagen NPs that were fabricated possessed a loading efficiency of 3.17 \(\pm\) 0.37%, entrapment efficiency of 76.7 \(\pm\) 2.4%, and displayed a regulated and slow release. Their study concluded that the encapsulation of silymarin into collagen NPs improved the therapeutic efficacy of silymarin by enhancing its bioavailability [69]. Surface modified collagen nanospheres which are delivered to the bloodstream are another favorable method for drug delivery to the brain. Modification of the surface in the spheres enables the identification of the particular surface receptors of the cell which allow their transcytosis through modification of the sphere properties such as surface charge and hydrophobicity, or blood-brain barrier (BBB) [70; 71]. [PERSON] et al. studied that the modification of surface in these nanospheres may allow surface receptor recognition of a particular cell which, in turn, allows the modification of the physiological properties of the nanospheres or the transcytosis through BBB, to help them pass over BBB through adsorption carried out by endothelial cells [72; 73; 74].  
Figure 10: Enhanced properties of collagen NPs in DDS and TE.  
[PERSON] et al. loaded gold NPs (Au) on hydroxyapatite (HAp) surface using a rapid microwave assisted technique. They prepared varied concentrations of Au-loaded nanostructures covered with collagen (Au-HAp-Col), which were enhanced for the loading and releasing of the doxorubicin drug, for applications in biomedicine. Collagen and Au-HAp NPs have an electrostatic interaction between them which makes a steady nanostructure. A ph-receptive release of approximately 53% and the highest efficiency of drug loading of approximately 58.22% were procured for 0.1 weight percent of Au-HAp-Col NPs. Their results demonstrated that these enhanced Au-HAp-Col NPs with bioactive and biocompatible characteristics could be useful for drug delivery, scaffold materials, cell growth, proliferation and adhesion [73]. In this study conducted by [PERSON] et al., silver NPs (DdAgNPs) were synthesized with collagen and doxycycline (DO) and its strength to be utilised as a bactericidal agent was evaluated. It was found that the DdAgNPs combined with collagen displayed stronger antibacterial action against all the test organisms compared to the DdAgNPs alone [74].  
Another study showed that collagen NPs can be helpful in tumor infiltration for anti-cancer drug delivery. This is due to the advantage of collagen which resembles the microenvironment of the tumor. In this study, they developed collagen-based tumor spheroids and optimized them using 95-D, U87 and HCT116 cells. The antitumor and delivery efficiencies of the drug-conjugated NPs in this model were studied through cytotoxicity and uptake studies. Their results demonstrated that the conjugated NPs reach the tumor cells by perforating into the gel matrix. This model was found to be more precise in figuring out the therapeutic results and dynamics of the drug transport agents in vivo, and in the demonstration of tumor biology, which fastens the drug discovery for cancer therapy [75]. Studies have also demonstrated that collagen NPs have been utilised as parenteral carriers for therapeutic and cytotoxic substances, such as hydrocortisone ([PERSON] et al.) and camptothecin ([PERSON] et al.) [8,76,77] These investigations on collagen in DDS are summarized in Table 2.