Lipid-based nanocarriers for breast cancer treatment – comprehensive review

Figures & data

Table 1. Advantages and limitations of lipid nanoacarriers.

Lipid nanocarriers	Advantages	Disadvantages	Reference
Liposomes	• Ease of formulation in pegylated (Stealth) liposomes • Stealth coating prolongs the systemic circulation time • Effective therapy for multidrug-resistant and other tumors • Capable of altering pharmacokinetics and bio-distribution • Reduces cardio-toxicities • Lipids used are compatible of parenteral administration • Can be used for drug resistant tumors	• Has stability issues • Ligands present in active targeted liposomes may affect the stability of the formulation	(Allen & Martin, 2004; Gabizon et al., 2006)
Solid lipid  nanoparticles	• Protection of drug from degradation • Has long-term stability • Reduces systemic toxicity • Feasible to load lipophilic and hydrophilic drugs • Easy scale up	• Inherent low drug loading capacity due to the crystalline structure of solid lipid • Drug expulsion • Unpredictable agglomeration • Higher incidence of polymorphic transitions	(Mukherjee et al., 2009; Patidar et al., 2010; Kaur & Slavcev, 2013)
Nanostructured  lipid carriers	• This drug delivery system developed to avoid the problems associated with the SLNs • Increased drug payload • Drug expulsion during storage • High water content of SLN dispersions	• Not feasible for thermo-labile drugs • Metal contamination during probe-sonication • Usage of large volume of aqueous phase may lead to higher dilution of dispersion	(Müller et al., 2002a; Iqbal et al., 2012)
Lipid polymer hybrid  nanoparticles	• Desirable particle size • Provision for surface modification • Higher drug payload • Entrapment of hydrophilic and lipophilic drugs • Amenable drug release pattern • High serum stability	• Lab-scale preparation is cumbersome • Not tunable for industrial scale production • Aseptic processing makes expensive	(Hadinoto et al., 2013; Mandal et al., 2013)

Figure 1. (a) Liposome, (b) active targeted liposome, (c) solid lipid nanoparticles, (d, f) nanostructured lipid carriers, (e) lipid polymer hybrid nanoparticles.

Figure 2. Summary of targets for the induction of apoptosis or inhibition of anti-apoptosis, angiogenesis, cell-cycle arrest and signal transduction in the breast cancer treatment. EGFR, epidermal growth factor receptor; GPCR, G-protein-coupled receptors; HER, human epidermal growth factor receptor; IKK, inhibitor of NF-B kinase; mTOR, mammalian target of rapamycin; NF-B, nuclear factor-B; TRAIL, tumor necrosis factor-related apoptosis inducing ligand; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor. Adapted from Schlotter et al. (2008).

Table 2. Summary of studies on active targeted liposomes to breast cancer.

Target ligand	Drug	Cell surface target	Reference
Siale^x	Merphalan	Lectins	(Vodovozova et al., 2000)
Vasoactive intestinal peptide VIP, a 28-amino acid mammalian neuropeptide	Radionuclide (Tc99m-HMPAO)	Vasoactive intestinal peptide (VIP) receptors	(Dagar et al., 2003)
17β-estradiol	Anti-cancer gene	Estrogen receptor	(Reddy & Banerjee, 2005)
Herceptin	Paclitaxel	HER2	(Yang et al., 2007)
Anti-transferrin receptor antibody	HER2-Si-RNA	Transferrin receptor	(Pirollo & Chang, 2008)
Anti-HER2 Fab’	PE38KDEL	HER2	(Gao et al., 2009)
Herceptin	Melittin	HER2	(Barrajón-Catalán et al., 2010)
Luteinizing hormone-releasing hormone analog	Mitoxantrone	Luteinizing hormone-releasing hormone receptor	(He et al., 2010)
Estrone	Doxorubicin	Estrogen receptor	(Paliwal et al., 2010)
Anti-HB-EGF monoclonal antibody	Si-RNA	Epidermal growth factor receptor	(Gao et al., 2011)
Peptide	PRDM14Si-RNA	MCF-7 cell specific	(Bedi et al., 2011)
Cetuximab	Doxorubicin	Epidermal growth factor receptor	(Mamot et al., 2012)
Fab’ of anti-HB-EGF monoclonal antibody	Doxorubicin	Heparin-binding epidermal growth factor-like growth factor	(Nishikawa et al., 2012)
Trastuzumab	Curcumin Resveratrol	HER2	(Catania et al., 2013)
Chlorotoxin	Doxorubicin	Matrix metalloproteinases	(Qin et al., 2014)

Table 3. Solid lipids used in the preparation of SLNs.

Solid lipid	Chemotherapeutic agent	Methods of preparation	Reference
Palmitic acid	Tamoxifen	Microemulsion and precipitation method	Fontana et al. (2005)
Stearic acid/Glyceryl mono stearate	Tamoxifen	Solvent injection method	Hashem et al. (2013)
Compritol® 888 ATO	Camptothecin	Modified olvent emulsification and ultra-sonication method	Acevedo-Morantes et al. (2013)
Trimyristin and soybean lecithin	Docetaxel	High pressure Homogenization method	Yuan et al. (2014)
Trimyristin	Paclitaxel	Homogenization method	Lee et al. (2007)
Stearic acid/Glyceryl mono stearate	Emodin	High pressure Homogenization method	Wang et al. (2012)
Compritol® 888 ATO	Tryptanthrin	Hot homogenization method	Fang et al. (2011)

Table 4. Solid lipids and liquid lipids used in preparation of NLCs.

Solid lipid	Liquid lipid	Chemotherapeutic agent	Method of preparation	Reference
Glyceryl tripalmitate	Glyceryl tridecanoate	Quercetin	Phase inversion method	Sun et al. (2014)
Softisan 154	Olive oil	Tamoxifen	Melt emulsification method	How et al. (2013)
Glyceryl monostearate	Labrafil WL 2609 BS	Tamoxifen	Solvent diffusion method	Shete et al. (2013)
Stearic acid	Oleic acid	Doxorubicin/Paclitaxel	Solvent emulsification method	Zhang et al. (2008b)
PEG-DSPE	Oleic acid	Curcumin	Solvent diffusion method	Lin et al. (2015)
Stearic acid, Soybean phosphatidylcholine	Polyoxyl castor oil	Baicalein Doxorubicin	Emulsion-evaporation solidification method	Liu et al. (2015)

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