6.2.2 Folic acid functionalized solid lipid nanoparticles

The folate receptor (FR) is one of the most widely evaluated receptor for active targeting of anticancer therapeutics in the case of in breast cancer cells. Folic acid has many advantages over antibody ligands such as small size, nonimmunogenicity, non-toxicity, ease of handling, stability and low cost [56]. Several researchers had reported earlier that the FA functionalized SLNs were able to deliver the chemotherapeutic agent, particularly to the cancerous cells. Thus, FA functionalized SLNs co-encapsulated with Docetaxel (DTX) and Curcumin (CUR) were successfully developed to enhance its therapeutic efficacy against breast cancer cells. FA-stearic acid (FA–SA) conjugate was synthesized by classical 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDAC) chemistry and incorporated in the DTX-CUR-SLN. Additionally, PEG–stearic acid (PEG–SA) was incorporated to obtain FA-DTX-CUR-SLN. The DTX-CUR-SLN and FA-DTX-CUR-SLN formulations were found to be stable at refrigerated condition for 2 months. Both the formulations showed sign of instability at accelerated condition (25°C/65% RH). The developed FA functionalized SLNs exhibited improved pharmacokinetic parameters, superior cancer cell targeting efficiency, and improved therapeutic efficacy of DTX. Folic acid was believed to be responsible for the targeting efficacy of the developed SLNs to the breast cancer cell. This conjugated system showed significant increase in area under the curve and mean residence time of the drug. Co-conjugation (FA and PEG) to SLNs co-encapsulated with DTX and CUR responsible for synergistic activity of both DTX and CUR. Moreover, bioaccumulation of DTX in heart and kidney was found very low which signified avoidance of vital organ toxicity [57].
