Solid Lipid Based Nano-particulate Formulations in Drug Targeting DOI: http://dx.doi.org/10.5772/intechopen.88268

6.2 Solid lipid nanoparticles for passive breast cell targeting

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

has many advantages over antibody ligands such as small size, non-

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

immunogenicity, 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

The sphingosine-1-phosphate (S1P), phytosphingosine, ceramides, and sphingosine are the metabolites of sphingolipids and are reported as essential structural

6.2.3 Cetamide and trimethylphytosphingosine-iodide co-conjugated solid lipid

6.2.2 Folic acid functionalized solid lipid nanoparticles

avoidance of vital organ toxicity [57].

nanoparticles

110

6.2.1 Fucose conjugated solid lipid nanoparticles

Role of Novel Drug Delivery Vehicles in Nanobiomedicine

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 DTX-SLN could serve as a potentials alternative parenteral formulations of DTX [60].


#### Table 4.

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

List of SLNs and their different ligand conjugated form for breast cancer cell targeting have been summarized in Table 4.

following cataract surgery [68]. Chitosan (Cs) coated IMC loaded SLNs (IMC-Cs-SLN) were developed to deliver NSAID to the posterior segment of ocular tissues and for improving the pre-corneal residence time and transcorneal permeability characteristics. For surface modification of the developed SLNs, the chitosan was incorporated into the aqueous phase prior to preparation of the SLNs. The developed SLNs were stable in terms of drug loading, EE, and less drug expulsion during storage at 40°C for 90 days. The SLNs showed higher bioaccumulation of IMC in the ocular tissues. The IMC-Cs-SLN showed superior trans-membrane IMC permeation characteristics which were due to penetration enhancing properties

Betaxolol hydrochloride (BH) is widely used for the treatment of ocular hypertension and open-angle glaucoma in clinical therapeutics. However, it faces certain limitations like low bioavailability and pre-ocular retention, and some side effects.

Target Model Comments Ref.

Inhibition of expression of ANGPTL2mRNA, Reduction in angiogenesis area

Improvement of the retinal structure

Superior bactericidal activity

Improved biodistribution of IMC at posterior segment

Superior antifungal activity

Imaging, Superior cytotoxicity

Targeted delivery of DXM for ischemiareperfusioninduced injuryinduced AKI

Rabbit Significantly reduced inflammation, No irritation

[62]

[65]

[67]

[69]

[70]

[73]

[75]

[78]

Retina C57BL/6 mice

Retina 661W,

Aqueous humor

Posterior segment of ocular tissue

Cornea and Conjunctiva

Upper posterior eye

Colorectal part

E-selectin receptor

RS1hdeficient mouse

Albino rabbit

White albino Rabbits

ARPE-19 & RCE Cell line, Rat

LoVo, CHO-K1

HUVECs, ICR male Mice

method

Solvent emulsification followed by evaporation

microemulsion method

homogenization

evaporationlow temperature solidification method

followed by high pressure homogenizer

Modified solventdiffusion method

diffusion method

List of SLNs and their different ligand conjugated forms for eye, colon and kidney targeting.

DXM Solvent

BH Emulsion

Hydration method followed by extrusion

7.2.2 Intercalated montmorillonite solid lipid nanoparticles

Solid Lipid Based Nano-particulate Formulations in Drug Targeting

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

SLN (Type) Lipid(s) Drugs Preparation

ANGPTL2 RNA

gene

03 SLN SA TMC Warm o/w

04 Cs-SLN GB IMC Hot

GMS

GMS, OA

06 PEG-SLNs COMP KTZ Emulsification

CP BAI (Drug) C IR-780 (Diagnostic agent)

CHO

02 SLN PRE Human RS1

of Cs [69].

Sl. no

01 SLN DSGPC,

05 Mt-SLNs PC,

07 Multifunctional SLNs

08 SIA-PEGylated SLN

Table 5.

113
