**3.3. Nature of polymer**

particle coalescence and stabilizes the formulation. In case where the lipid part is insufficient and the resulting electrostatic repulsive forces are weak, some agents like PEG can be incorporated in

The charge on lipid part which is responsible for electrostatic repulsion between particles is shielded when mixture of cationic and zwitterionic lipids is employed. Anionic heads of zwitterionic lipids face outwards which reduces of cationic lipids charge and promotes aggregation of particles. However, the higher cationic lipid concentration may overcome this charge screening and aggregation can be minimized [59, 99]. The zwitterionic lipid such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) produces less aggregation than a cationic lipid, 1,2-dipalmitoyl-3-trimethylammonium propane (DPTAP). Therefore, it zwitter ionic lipid

The two potential benefits that lipid augments to the HNPs are the encapsulation efficiency and retardant release of the incorporated drugs. The former is achieved by preventing drug leakage during self-assembling process, whereas the latter is due to reduced interaction of lipids with dissolution medium [17, 100]. The charge on the surface of lipids and drugs also affects the entrapment efficiency due to interaction of surface charge of HNPs and the charge of the drug. The loading of ciprofloxacin in the PLGA-PC hybrid system is not successful due

A significant higher percent encapsulation of docetaxel (59 ± 4) was achieved in HNPs assembled from lecithin, DSPE-PEG and PLGA i.e. compared to PLGA-PEG nanoparticles with 19 ± 3 (mean ± SD). This effect is attributed to the fencing action of lipids which keeps hydrophobic drugs within the core and retards water penetration. The lipid-polymer hybrid formulations also provide a sustained release of drug when compared with nonhybrid formulation due to less water penetration and reduced escape of drug molecules from polymeric core. A consistent 50 % release of docetaxel from lecithin-PLGA hybrid system was observed compared to the PLGA-PEG NPs and PLGA NPs released same amount of drug in 10 hours and 7 hours, respectively. The pH of the dissolution media also affected the encapsulation of drugs, for example, the erlotinib EE % was 77.1%, 28.83% and 18.45% at pH values

The steric stabilization of HNPs systems to withstand salt solutions, buffer actions and uptake by macrophages is provided by the appropriate surface modification by employing PEG. The term is called as PEGylation. PEGs can escalate circulation times of HNPs by preventing par-

Incorporation of PEG-lipid affects the colloidal stability of HNPs by two ways (i) chain length of PEG-lipid and (ii) molar Ratio of PEG-lipid. HNPs coated with PEG-lipid longer chains exhibited more stability than the shorter chain PEG-lipid coated particles. Similarly, at the fixed chain length more PEG-lipid incorporated onto polymer core and thickness of lipid shell

increased which lowered the zeta potential and hence stability is enhanced [78, 80].

ticle aggregation, opsonization and adsorption of plasma proteins [27, 78].

the formulations to provide steric repulsion and stabilization of the HNPs [52, 80–98].

provides more stability than ionic lipids [55, 59].

68 Advanced Technology for Delivering Therapeutics

of 7.4, 5.4 and 3.4, respectively [55, 59, 78, 100].

**3.2. PEGylation**

to the interaction of cationic drug with the anionic lipids [19, 78].

The characteristics such as density and surface charge play an important role in the fabrication of HNPs [35]. The density of polymer also has substantial effect on stability and particle size [59, 78]. HNPs fabricated from high density polymer are less stable toward increasing ionic strength of medium due to the higher sedimentation rate when electrostatic charges are shielded. PLA is 1.18 times denser than poly(styrene); hence, HNPs prepared with PLA core have less colloidal stability toward increasing ionic strength of medium [35]. Zhang et al. evaluated that change in viscosity of PLGA polymer from 0.19 to 0.82 resulted a decrease in particle diameter from 92.7 nm to 66.7 nm [59].

Adsorption of lipid over polymeric particle surface to form lipid shell depends upon curvature and surface charge of particle. Cationic lipids exhibit more adsorption than zwitter ions toward the anionic polymeric core due to the electrostatic attractions polymeric core from anionic polymer PLA has greater affinity for DPTAP cationic lipid than the zwitterionic DPPC. Lipid rearrangement around polymeric core can be quick and complete if the affinity between polymer and lipid is high. Larger size distribution and free lipid structures are observed when lipids cannot rearrange around polymeric core due to weaker affinity. Modification in pH of medium can improve the affinity of polymer for lipid by surface charge variation at different pH levels [35, 101, 102].
