**3. Method of preparation**

Various formulation methods have been designed and employed for the preparation of LPHNPs based on the chemical and physical nature of the structural components and the desired therapeutic purpose or outcome. These hybrid DDS include the lipid-polymer, lipid metal, polymer-inorganic hybrid, metal (Gold, Silver or Iron) along with polymer hybrid NPs have investigated and employed for the clinical use. Conventionally, two different approaches have been investigated including the two-step and single-step processes. First approach employed the mixing of the inner core and the outer layers to prepare the LPHNPs. While the single-step approach the lipid and polymer that are assembled using the different mechanisms to form the LPHNPs that overcome the drawback of individual components.
