**3.1 Two-step conventional method**

Two-step method was the most primitive and frequent method applied for the preparation of different hybrid nanoparticles and other DDS. In the method, the different layers comprise of structurally, different components were separately fabricated and then co incubated to make a complete particle by using the various approaches including the adsorption, self-assembling and encapsulation. The core and shell morphology might be obtained and the various hybrid nanoparticles were obtained by using the sonication [19], solvent emulsification, solvent evaporation [13], nanoprecipitation [20], extrusion, high speed homogenizers and other techniques. However, the selection of the method is based on the physicochemical properties of the loaded drug, size of the core particle and the desired properties that you want to introduce in the NP formulation [18]. For example, the single-step method has been chosen when the encapsulating materials are miscible with the coating substance and soluble in the organic solvent [21].

This method involves multiple preparatory steps to prepare the polymeric core materials and then the lipid vesicles by the different techniques. The polymeric core material might be prepared by dissolving the polymer in a suitable solvent and then precipitated into some nonsolvent phase. Finally, the both components are co-incubated and mixed under gentle stirring for certain time period to allow them to get assembled into lipid-polymer hybrid particles [22, 23]. The mixing may be carried out by vortexing, thin film hydration, probe sonication or extrusion processes so that the final LPHNPs were obtained. These processes actually provide the energy for the mixing, layering or adsorption of the outer coating material on the polymeric core material that might be strengthen by the electrostatic forces among these structural components.

**63**

*Lipid Polymer Hybrid Nanoparticles: A Novel Approach for Drug Delivery*

grade of PLG and PLA using the freeze-drying method [26, 27].

that either make the matrix or core shell morphology [29].

solvent evaporation method and solvent diffusion method.

Different modifications have been suggested in the conventional two-step process for the fabrication of the LPHNPs. These modifications might include the use spray drying and lithographic molding along with the freeze drying [24]. The inner central core of the NPs have been prepared with the process that further suspended or dispersed in any suitable organic solvent containing the different structural components of the LPHNPs [2]. Different studies indicate the formulation of LPHNPs loaded with various antibiotics agents including levofloxacin, ciprofloxacin and isoniazid in the form of freeze dried powders for the inhalation therapy that were entrapped in the mono or multiple layers of the lipid shell. The coating of the lipid might provide the core shell morphology to the NPs. This modification in the preparation of the NPs added advantage in term of better inhalation efficiency and greater control on the overall average particle size of the LPHNPs relative to the conventional method [25]. The nanoparticles and hybrid microfiber fabrication are the some other examples that utilized the polyglutamic acid, poly lysine and various

The poor entrapment and easy leakage of the drug from the polymeric core of the LPHNPs prepared by the conventional two-step methods urged the development of some newer methods that overcome these shortcomings and enhance the therapeutic efficiency of the prepared formulation [14, 28]. The development of single-step method provides the way to control the particle size, PDI, uniformity of the structural components. It also overcomes the variability in different batches and other properties of the LPHNPs in term of their physicochemical properties and stability. The method involves the single preparatory step that considers the mixing of two different phases containing the lipid and polymer in each of the given phase. The mixing process followed by the self-assembling of the structural components

Various techniques in the single-step preparation method might include the single or double emulsification method, sonication technique, nanoprecipitation,

LPNs have been prepared for efficient encapsulation and delivery of the wide range of therapeutic agents either alone or in combinations. LPNs have wide range of applications in cancer therapy and delivery of protein based therapeutic agents, i.e., small interfering RNA, nucleic acid and genes delivery etc. Additionally, LPNs can be used for oral drug delivery of many drugs [46]. LPN has wide range of applications in gene and DNA delivery, vaccines and diagnostic imaging agents as

Doxorubicin loaded polymer-lipid hybrid nanoparticles (Dox-PLN) were designed and injected intratumorally in mice. At a dose of 0.1 and 0.2 mg, 70 and 100% tumor growth delay was observed, respectively. Dox-PLN treated mice have not shown any sign of toxicity and only 2 mice out of 15 exhibited transient fur

*DOI: http://dx.doi.org/10.5772/intechopen.88269*

**3.2 Modified two-step method**

**3.3 Single-step preparation method**

**4. Biomedical applications**

shown in **Figure 2** [2].

**4.1 Cancer therapy**
