# Collagen Nanoparticles in Drug Delivery Systems and Tissue Engineering
## 2 Methods of Collagen Nanoparticle Preparation
### Polymer Chain Collapse
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Preparation Method** & **Advantages** & **Limitations** & **References** \\ \hline \multirow{3}{*}{Emulsification/Solvent Extraction} & Process is simple, equipment required is simple, recovery can be controlled, high flexibility and selectivity & Require stabilizer and surfactant because of unstable thermodynamic nature, need to add organic solvent and then remove it, residues of organic solvent may be toxic & [10, 34] \\  & Particles formed are very stable, NPs of smaller size, by guiding process conditions, nanoparticle & Hard process to scale up & [36, 65] \\  & size and shape can be controlled, can be combined with sensitive drugs & & \\ \hline \multirow{3}{*}{Phase Separation} & Specialized apparatus is not necessary, particle size controllable by altering polymer solution concentration, uniform particles are formed & Limited particle size diameter, small-scale production, organic solvent requirement & [43, 44] \\ \hline \multirow{3}{*}{Nano Spray drying} & Economical process, simple to carry out experimentally, encapsulation of hydrophilic drugs takes place easily, beneficial for heat-sensitive samples as it helps maintain temperature of the nanoparticle droplets & Small scale production, difficult to integrate hydrophobic drugs, reduced encapsulation efficiency, great energy consumption & [45, 46] \\  & Can be scaled for industrial use, good drug loading efficiency, ease of particle synthesis due to single-step processing, formation of dry particles & Reduced flow, could produce degradation of macromolecules & [49, 50] \\ \hline \multirow{3}{*}{Self-Assembly} & Highly stable process, small NPs can be formed with high encapsulation efficiency & Hard to control NP size, shape and the potential of protein strain exists & [27, 54] \\ \hline \multirow{3}{*}{Desolvation/Simple Coacervation} & Increased encapsulation efficiency, Size and shape of NPs can be controlled using reaction conditions. & Can be carried out only for proteins influenced by dissolution or diluted by carrier proteins & [31, 55] \\  & Economical, easy experimentation, controllable NP size, large scale prodcution & Chamber has to be cooled due to heat release, uncontrollable NP shape, can be carried out only for coarse NPs & [57] \\ \hline \multirow{3}{*}{Interfacial Polymerization} & \multirow{3}{*}{Easy to carry out, inessential monomer purity} & Expensive polymer monomer, takes a lot of time to be carried out & [59, 60] \\  & & & \\ \hline \multirow{3}{*}{Polymer Chain Collapse} & Controllable NP properties, high stability, enhanced spherical shape particle production & Limited particle diameter, hard to control side reaction occurrence & [62, 63] \\  & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Advantages and limitations of collagen NP preparation methods. Figure 9: Polymer Chain Collapse—Distinct molecules are fabricated due to the precursor chain control that can direct the nanoparticle properties. Through intramolecular crosslinking, the polymer is fabricated to form single chain polymer NPs that find various applications in the human body.