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

Garg, Jivesh; Pathania, Khushboo; Sah, Sangeeta Pilkhwal; Pawar, Sandip V.

doi:10.1186/s43094-022-00414-8

Future Journal of Pharmaceutical Sciences

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
S. No.	Liquid lipid used	Drug loaded	Synthesis method	MPS and EE	Cell line(s) and animal model(s) used	Key findings	References
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]
	Tripalmitin				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				BALB-C nude female mice bearing A172 xenografts
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]
2	Capmul MCM	Curcumin	Hot HPH method	146.8 nm and 90.86%	Male Wistar rats	Increased drug delivery across BBB	[234]
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]
3	Oleic acid	Artemisinin	Solvent evaporation method	145 ± 12.5 nm and 82.3 ± 7.3%	U87MG		[236]
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]
4	Triolein	Paclitaxel	Solvent evaporation method	205.4 ± 11 nm and 91.8 ± 0.5%	U87MG		[237]
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]
5	Oleic acid	Cytarabine	Melt emulsification–ultrasonication and lyophilization	96.94 ± 1.81 nm and 49.5 ± 2.24%	EL4		[238]
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]
6	Vitamin E	Temozolomide	Hot HPH method + Ultrasonication	131.58 nm and 81.64 ± 3.71%	Wistar rats	Increased brain targeting efficiency (rose by 457%) Enhanced drug uptake and retention in the brain	[239]
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]
7	Polyoxyl castor oil (Cremophor ELP)	Temozolomide	Solvent diffusion technique	121.4 ± 5.6 nm and 81.4 ± 3.7%	BALB/c nude mice	Reduced tumour volume (by 85%) in 21 days	[240]
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]
	Compritol® 888 ATO				BALB/c nude mice	Higher tumour inhibition (83.3%) Higher tumour growth inhibition (4 times) than drug
	Polyoxyl castor oil (Cremophor ELP)				BALB/c nude mice
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]
9	Polyoxyl castor oil (Cremophor ELP)	Temozolomide and vincristine	Solvent diffusion technique		BALB/c nude mice	Excellent tumour growth inhibition activity in vivo (83.17%)	[242]
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]
10	Polyoxyl castor oil (Cremophor ELP)		Solvent diffusion technique	178.9 ± 2.7 nm and 82.7 ± 2.5%	BALB/c nude mice	Enhanced in vivo anti-proliferative activity (3.3 times higher than drug solution) Boosted brain targeting of the drug	[139]
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]
11	Oleic acid and Vitamin E TPGS	SN38 (metabolite of irinotecan)		148.10 ± 2.71 nm and 81.36 ± 0.69%	U87MG		[244]
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]
13	Sesame oil	Resveratrol	Hot emulsification homogenization method	317.7 ± 15.9 nm and 77.42 ± 3.76%	Isolated sheep nasal mucosa (for permeation studies)		[248]
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]
14	Isopropyl myristate /Isopropyl palmitate /Isopropyl stearate	Ferulic acid	Phase inversion temperature method	< 50 nm and 90.7 ± 4.48%	U87MG	Exhibited slow drug release Enhanced cytotoxic activity	[249]
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]
15	Isopropyl stearate	Ferulic acid	Phase inversion temperature method	150–200 nm and 90.5 ± 0.94%	U87MG		[250]
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]
16	Medium chain triglycerides	Hesperetin	Phase inversion temperature method	< 80 nm and 72.7 ± 0.92%	T98G		[251]
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]
17	Refined hydrogenated kernel palm oil	Garlic oil	Hot HPH method	136.8 ± 0.56 nm and 83.26 ± 6.13%	U87MG		[252]
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]
18	Propylene glycol monolaurate (Lauroglycol® 90) /Propylene glycol monocaprylate (Capryol®) /Caprylocaproylmacrogol-8- glycerides (Labrasol®) / polyoxyl-15-hydroxystearate (Kolliphor® HS15)	Docetaxel	Hot HPH method	123.3 ± 0.642 nm and 99.13 ± 1.2%	SVG P12, U87MG, RAW 264.7 and BTNW911		[253]
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]
19	Glycerol trioleate	Dihydroartemisinin	Solvent volatilization and ultrasonic melting technique	130 nm and 81.63%	ICR mice	Increased drug accumulation in brain Excellent tumour targeting ability Prolonged drug circulation time Increased tumour growth inhibition	[254]
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]
20	Capmul (glyceryl mono-dicaprylate)	Docetaxel and pomegranate seed oil	Melt emulsification method	169.7 ± 16.67 nm and 63.23 ± 2.725%	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)	[255]
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]
21	Oleic acid	Paclitaxel and doxorubicin	Melt emulsification method	122.83 ± 1.97 nm	Nude female mice	Increased apoptosis No conspicuous adverse effects Decreased expressions of PI3K, Akt, Cd133 and mTOR	[256]

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

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