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Table 3 Analysis of various research studies that employed NLCs as drug carriers for delivering anticancer drugs across the blood–brain barrier

From: Nanostructured lipid carriers: a promising drug carrier for targeting brain tumours

S. No. Solid lipid used Drug loaded Synthesis method MPS and EE Cell line(s) and animal model(s) used Key findings References
Liquid lipid used
1 Tripalmitin Curcumin Hot HPH method 214 nm and 88.6% A172 Increased inhibitory action (from 19.5% to 82.3%)
Increased cellular ROS levels (2.6 times greater than control)
[233]
BALB-C nude female mice bearing A172 xenografts Increased bioavailability (by 6.4 times)
Prolonged half-life (from 3.1 to 5.7 h)
Reduction in tumour volume (by 82.3%) in a short time span (19 days)
Oleic acid
2 Precirol ATO5 Curcumin Hot HPH method 146.8 nm and 90.86% U373MG and isolated sheep nasal mucosa (for permeation studies) NLCs permeated quickly from the nasal mucosa to the brain (76.71% in 11 h)
Enhanced antitumour efficacy
[234]
Capmul MCM Male Wistar rats Increased drug delivery across BBB
3 Compritol® Artemisinin Solvent evaporation method 145 ± 12.5 nm and 82.3 ± 7.3% U87MG Enhanced aqueous solubility, site-specificity, drug targeting, and permeation of the artemisinin across BBB [236]
Oleic acid
4 Cholesterol Paclitaxel Solvent evaporation method 205.4 ± 11 nm and 91.8 ± 0.5% U87MG Exhibited sustained drug release (over 3 days)
Enhanced anti-proliferative activity (at concentrations between 0.938 and 1.17 µM)
[237]
Triolein
5 Stearic acid Cytarabine Melt emulsification–ultrasonication and lyophilization 96.94 ± 1.81 nm and 49.5 ± 2.24% EL4 Formulation exhibited dual release (an initial burst release followed by sustained release for 3 days)
Enhanced cytotoxic activity on EL-4 cells
Better stability of the formulation
[238]
Oleic acid
6 Gelucire Temozolomide Hot HPH method + Ultrasonication 131.58 nm and 81.64 ± 3.71% Porcine nasal mucosa Prolonged drug release
Enhanced drug permeation across BBB through the nasal mucosa
[239]
Vitamin E Wistar rats Increased brain targeting efficiency (rose by 457%)
Enhanced drug uptake and retention in the brain
7 Compritol® 888 ATO Temozolomide Solvent diffusion technique 121.4 ± 5.6 nm and 81.4 ± 3.7% U87MG Significantly reduced the viability of malignant cells [240]
Polyoxyl castor oil (Cremophor ELP) BALB/c nude mice Reduced tumour volume (by 85%) in 21 days
8 Compritol® 888 ATO Temozolomide Solvent diffusion technique 118.3 ± 2.6 nm and 84.7 ± 3.2% U87MG Sustained drug release (up to 24 h)
Higher cytotoxicity (10 times) than drug solution
[241]
BALB/c nude mice Higher tumour inhibition (83.3%)
Higher tumour growth inhibition (4 times) than drug
Polyoxyl castor oil (Cremophor ELP)
9 Compritol® 888 ATO Temozolomide and vincristine Solvent diffusion technique 117.4 ± 2.8 nm and 88.9 ± 3.6% (for temozolomide) and
85.4 ± 2.8% (for vincristine)
U87MG Sustained release of both drugs (over 36 h)
Dual drug-loaded NLCs exhibited better cytotoxic activity than their single drug-loaded counterparts
[242]
Polyoxyl castor oil (Cremophor ELP) BALB/c nude mice Excellent tumour growth inhibition activity in vivo (83.17%)
10 Compritol® 888 ATO Enhanced green fluorescence protein plasmid (DNA) and temozolomide Solvent diffusion technique 178.9 ± 2.7 nm and 82.7 ± 2.5% U87MG Higher antitumour activity (4 times) than drug solution
Greater transfection efficiency
[139]
Polyoxyl castor oil (Cremophor ELP) BALB/c nude mice Enhanced in vivo anti-proliferative activity (3.3 times higher than drug solution)
Boosted brain targeting of the drug
11 Cetyl palmitate SN38 (metabolite of irinotecan) Hot ultrasonication and solvent evaporation/ modified emulsification solvent evaporation method 148.10 ± 2.71 nm and 81.36 ± 0.69% U87MG Drug was released in three phases
Higher cytotoxicity than drug
No remarkable toxicity
Higher cellular uptake
[244]
Oleic acid and Vitamin E TPGS
12 Glyceryl mono stearate Quercetin Hot HPH method 118.2 nm and 88.74% U373MG and isolated sheep nasal mucosa (for permeation studies) Sustained drug release
Significantly higher permeation rate
No remarkable toxicity on nasal mucosa
[246]
Capmul GMO
Higher local drug concentration in the brain
Enhanced bioavailability
Male Wistar rats
13 Glycerol monostearate Resveratrol Hot emulsification homogenization method 317.7 ± 15.9 nm and 77.42 ± 3.76% Isolated sheep nasal mucosa (for permeation studies) Exhibited dual drug release
Higher free radical scavenging activity
Exhibited highest cumulative permeation
[248]
Sesame oil
14 Cetyl palmitate Ferulic acid Phase inversion temperature method  < 50 nm and 90.7 ± 4.48% U87MG Exhibited slow drug release
Enhanced cytotoxic activity
[249]
Isopropyl myristate /Isopropyl palmitate /Isopropyl stearate
15 Cetyl Palmitate Ferulic acid Phase inversion temperature method 150–200 nm and 90.5 ± 0.94% U87MG Significant drop in cellular viability
High reduction in ERK1/2, c-Myc, Bcl-2 expression levels
Induced apoptosis
[250]
Isopropyl stearate
16 Glyceryl behenate Hesperetin Phase inversion temperature method  < 80 nm and 72.7 ± 0.92% T98G Prolonged drug release
Higher cytotoxic activity
Greater stability
[251]
Medium chain triglycerides
17 Cetyl palmitate Garlic oil Hot HPH method 136.8 ± 0.56 nm and 83.26 ± 6.13% U87MG Long-term stability
Two times higher drug release than free garlic oil
Higher therapeutic efficiency
Increased permeation across the BBB
More potent induction of apoptosis
Enhanced anticancer activity
Increased inhibition of cell migration and cell invasion
Enhanced therapeutic efficiency of garlic oil
[252]
Refined hydrogenated kernel palm oil
18 Dynasan 114 Docetaxel Hot HPH method 123.3 ± 0.642 nm and 99.13 ± 1.2% SVG P12, U87MG, RAW 264.7 and BTNW911 Exhibited biphasic drug release
Higher drug uptake by cancerous cells
Excellent stability
Effectively inhibited the cancer cells growth
[253]
Propylene glycol monolaurate (Lauroglycol® 90) /Propylene glycol monocaprylate (Capryol®) /Caprylocaproylmacrogol-8- glycerides (Labrasol®) / polyoxyl-15-hydroxystearate (Kolliphor® HS15)
19 Cholesterol Dihydroartemisinin Solvent volatilization and ultrasonic melting technique 130 nm and 81.63% C6, bEnd.3, HUVECs, HepG2, and B16 Improved drug release rate
Enhanced cellular uptake of biomimetic NLCs
Exhibited strong anti-proliferative activity
Increased permeation across BBB and BTB
[254]
Glycerol trioleate ICR mice Increased drug accumulation in brain
Excellent tumour targeting ability
Prolonged drug circulation time
Increased tumour growth inhibition
20 M-Lipid Docetaxel and pomegranate seed oil Melt emulsification method 169.7 ± 16.67 nm and 63.23 ± 2.725% MCF7, DU145, U87MG, and NCI-H460 Exhibited zero-order drug release
Long-term stability (for 12 months)
Excellent cytotoxic activity (20 times higher than marketed formulation)
[255]
Capmul (glyceryl mono-dicaprylate) Male Sprague Dawley rats Improved chemotherapeutic potential
Longer residence of the drug in the blood
Higher volume of distribution and lower clearance
Increased half-life (by 3.5 times)
21 Compritol® 888 ATO Paclitaxel and doxorubicin Melt emulsification method 122.83 ± 1.97 nm CD133-positive U87 cells Exhibited strong anti-proliferative activity [256]
Oleic acid Nude female mice Increased apoptosis
No conspicuous adverse effects
Decreased expressions of PI3K, Akt, Cd133 and mTOR
  1. A172, human brain cancer line; U373MG, human astrocytoma–glioblastoma cell line; U87MG, human primary glioblastoma cell line; EL4, mouse ascites lymphoma lymphoblast cell line; T98G, human glioblastoma multiforme tumour cell line; SVG P12, human non-cancerous foetal glial cell line; RAW 264.7, monocyte/macrophage cell line; BTNW911, cells from a 60-year-old male having grade IV glioblastoma; C6, rat glial tumour cells; bEnd.3, mouse brain microvascular endothelial cells; HUVECs, human umbilical vein endothelial cells; HepG2, human liver cancer cell line; B16, murine melanoma cell line; MCF7, human breast cancer cell line; DU145, human prostrate carcinoma cell line; NCI-H460, human non-small lung cancer cell line