4.2.4 Apolipoprotein E conjugated solid lipid nanoparticles

Low density lipoprotein (LDL) receptors are overexpressed on the BBB and apolipoprotein E (AP-E), a plasmatic protein is easily recognized by these receptors. Resveratrol (RSV), polyphenolic flavonoid promises to offer neuroprotective effects which are helpful in neurological disorders like Alzheimer's, Parkinson's, Huntington's diseases, brain ischemia, and epilepsy. The AP-E conjugated resveratrol (RSV) SLNs were successfully developed. The binding of ApoE to the SLNs surface was carried out by spontaneous interaction between the previously biotinylated ApoE and the covalently attached avidin on the SLNs surface, resulting


Table 2.

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

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

incorporating MMP-cleavable lipopeptide. The in vitro study indicated that the developed SLNs showed higher uptake and gene knockdown efficacy. SLNs also showed low cytotoxicity which was owing to masking of intrinsic positive charge of SLNs by PEGylated cleavable lipopeptide. In in vivo studies, angiopep functionalization played a vital role as a mediator of transport across the BBB and targeting

Low density lipoprotein (LDL) receptors are overexpressed on the BBB and apolipoprotein E (AP-E), a plasmatic protein is easily recognized by these receptors. Resveratrol (RSV), polyphenolic flavonoid promises to offer neuroprotective effects which are helpful in neurological disorders like Alzheimer's, Parkinson's, Huntington's diseases, brain ischemia, and epilepsy. The AP-E conjugated resveratrol (RSV) SLNs were successfully developed. The binding of ApoE to the SLNs surface was carried out by spontaneous interaction between the previously

biotinylated ApoE and the covalently attached avidin on the SLNs surface, resulting

DTX Lf

CRM Tf and Lf Receptors

RSV LDL

Receptors

siRNA Angiopep bEnd.3 cell,

Receptor

CMP Brain Human

Drugs Target Model Comments Ref.

Enhanced accumulation of CMP. Superior in vitro antitumor activity

bioaccumulation of RLZ in brain.

sustained drug release kinetics

Improved the brain targeting potential

Higher BBB permeability. Superior antiproliferative action

Higher uptake and gene knockdown efficacy

Brain targeted delivery of RSV [33]

[34]

[35]

[37]

[39]

[41]

[42]

glioma & Monocytic cell line. Wistar rats

RLZ Brain Male SD rats Higher

VIN Brain — Zero-order

U-87 MG cell lines & Swiss albino mice

U87MG, HBMECs

U87MG cells,

hCMEC/D3 Cell line

4.2.4 Apolipoprotein E conjugated solid lipid nanoparticles

Role of Novel Drug Delivery Vehicles in Nanobiomedicine

Preparation method

High shear homogenization

ultrasonication techniques

Warm oil-inwater microemulsion technique

High shear homogenization

ultrasonication techniques

Emulsification and solvent evaporation method

Homogenization followed by centrifugation

Detergent dialysis technique

homogenization followed by sonication technique

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

CP High shear

and

and

to glioma [41].

Sl. no SLN (Type)

01 SLN CP,

02 SLN COMP,

03 SLN SA,

04 Lf-SLN GMS,

06 SLN POPC,

05 Tf-Lf-SLNs

07 AP-E - SLNs

Table 2.

104

Lipid (s)

DMPC

SPC

GMS, PRE, GTP

SA, SL

TPM, DSPE

DSPE, CHO, DM

in two different ApoE-functionalized SLNs: SLN-DSPE-ApoE and SLN-Palmitate-ApoE. These conjugated SLNs were sufficiently stable and were able to prevail over the issues of RSV like low solubility, degradation but also to help its brain targeted delivery. Brain targeted delivery of RSV by such SLNs follows a bi-stage system. The AP-E-RSV-SLNs mimic lipoprotein particles that are endocytosed into the BBB endothelium via the LDL receptor and then transcytosed to the brain [42].

List of SLNs and their different ligand conjugated forms for brain cell targeting have been summarized in Table 2.
