6.2 Solid lipid nanoparticles for passive breast cell targeting

#### 6.2.1 Fucose conjugated solid lipid nanoparticles

Fucose receptors are overexpressed in the breast cancer cell. Thus, conjugation of fucose to SLNs was proposed to deliver the drug specifically to breast cancerous cells. Fucose conjugated methotrexate (MTX) loaded SLNs were developed to achieve enhanced targeting potential for breast cancer cells. Fucosylation of MTX-SLNs was related with opening of fucose ring and reaction of its aldehyde group with free amino functionalities expressed over the surface of MTX-SLNs in sodium acetate buffer (pH 4.0). The above process led to the formation of Schiff's base (– N=CH). The Schiff's base might be reduced to secondary amine (–NHCH2) and establish equilibrium with Schiff's base. Physical stability of prepared SLNs was higher which could be due to positive zeta potential value that provides repulsive interaction between nanosized lipid particles preventing particle aggregation. The ex vivo study revealed higher cellular uptake as well as higher cytotoxicity at lower IC50 of MTX. The in vitro study results showed increased rate apoptosis with a change in lysosomal membrane permeability and a higher rate of lysosomal membrane degradation. The in vivo study revealed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution to other organs [55].

components of cell membranes or important mediators of cellular process that regulate the proliferation, survival, and death of cells. Moreover, sphingosines including N,N,N-trimethylsphingosine (TMP-I) have been reported for their role as a negative modulator of transmembrane signaling through protein kinase C (PKC) as well as an inhibitor of sphingosine kinase-1 (SK-1), controlling the various membrane-associated signaling mechanisms associated with cell growth and inhibitory apoptosis in tumor cells [58]. Ceramide, a kind of sphingosine conjugated with fatty acid residue, is also reported to enhance the sensitivity of MDR-acquired cancer cell lines to chemotherapeutic agents [59]. Thus, attempts were made to employ ceramide (CD) and trimethylphytosphingosine-iodide (TMP-I) as a targeting agent for docetaxel (DTX) loaded SLNs. The prepared SLNs were physically stable without any significant change in their physical appearance, drug content, and particle size over a period of 8 weeks at 4°C. CD enhanced the DTX sensitivity in MDR-acquired cancer cell lines. In vivo clearance of drug and tumor growth inhibitors were significantly decreased in case of CD and TMP-I conjugated SLNs when compared with the marketed product. Thus, CD and TMP-I conjugated

Solid Lipid Based Nano-particulate Formulations in Drug Targeting

DOI: http://dx.doi.org/10.5772/intechopen.88268

DTX-SLN could serve as a potentials alternative parenteral formulations of

Target Model Comments Ref.

Exhibited improved phototoxicity and anticancer efficacy

Possessed superior anticancer activity with reduced toxic effect.

Improved bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs.

Synergistic cancer efficacy due to coencapsulation of DTX and CRM along with targeted delivery of drugs

Significant increased antitumor efficacy with targeted drug delivery

[53]

[54]

[55]

[57]

[60]

method

and ultrasonication method

Hot

homogenization

homogenization method

microemulsion method

Modified ethanol injection method

homogenization method

List of SLNs and their different ligand conjugated forms for breast cancer cell targeting.

Breast Cancer cell

Breast Cancer cell

Fucose Receptor

Folic acid Receptor

CD & TMP-1 4T1, MDA-MB-231, Female Nu/Nu mice- MDA-MB-231

MCF-7 and HUVEC cell line

MCF-7 Cell line & Female SD rat

MCF-7 &MDA-MB-231Cell line. Female Wistar Rat

MCF-7 cell, MCF-7/ADR cells

Lipid(s) Drugs Preparation

complex

MTX Hot

PC, TMS, DTX High-pressure

01 SLN TD TMP Modified hot

COMP Mn (II)

DTX [60].

Sl. no SLN (Type)

02 Mn (II) Complex-SLN

04 FA-PEG-SLN

05 CD-TMP I-SLN

Table 4.

111

03 F-SLN PL90NG,

PL, STA, GEL

GMS, SA CUR, DTX
