Enhanced permeability of blood–brain barrier and targeting function of brain via borneol-modified chemically solid lipid nanoparticle

Figures & data

Figure 1 Synthetic route of BO-DOPE as one of the lipid materials of BO-SLN/CM.

Abbreviations: BO, borneol; DOPE, dioleoyl phosphoethanolamine; BO-SLN/CM, borneol-modified chemically solid lipid nanoparticle.

Table 1 The composition of SLN, BO-SLN/PM and BO-SLN/CM

Sample	BO (mg)	BO-DOPE (mg)	SA (mg)	PEG-SA (mg)	Lecithin (mg)	Brij S10 aqueous sollution (mL)
SLN	–	–	5	5	5	12
BO-SLN/PM	0.4	–	5	5	5	12
BO-SLN/CM	–	5	5	5	5	12

Abbreviations: BO, borneol; BO-SLN/CM, borneol-modified chemically solid lipid nanoparticle; BO-SLN/PM, borneol-modified physically solid lipid nanoparticle; PEG-SA, polyethylene glycol monostearate; SLN, solid lipid nanoparticle.

Figure 2 (A) ¹H and (B) ¹³C NMR spectrum of DOPE, (C) ¹H and (D) ¹³C NMR spectrum of BO-DOPE.

Abbreviations: BO, borneol; DOPE, dioleoyl phosphoethanolamine; NMR, nuclear magnetic resonance.

Table 2 Comparison of the four methods of preparation

Method	Particle size (nm)	PDI	Stability (7 days)
Emulsion and solvent evaporation	199.1	0.088	+
Microemulsion method	441.4	0.299	+
Water/oil/water double emulsion and solvent evaporation	138.4	0.108	−
Thin-film evaporation and ultrasonic dispersion	181.8	0.140	−

Notes: −, homogeneous system; +, flocculation or sedimentation.

Abbreviation: PDI, polydispersity index.

Figure 3 Relationship between particle diameter and (A) lecithin ratio, (B) BO-DOPE/PEG-SA, (C) emulsification method, (D) ultrasound power, and (E) ultrasound time.

Abbreviations: BO, borneol; DOPE, dioleoyl phosphoethanolamine; PEG-SA, polyethylene glycol monostearate.

Table 3 Intensity diameter distribution and zeta potential of SLN, BO-SLN/PM, and BO-SLN/CM

Sample	Diameter (nm)	PDI	Zeta potential (mV)
SLN	87.0	0.088	−24.59
BO-SLN/PM	87.8	0.108	−23.29
BO-SLN/CM	86.9	0.017	−24.97

Abbreviations: BO, borneol; BO-SLN/CM, borneol-modified chemically solid lipid nanoparticle; BO-SLN/PM, borneol-modified physically solid lipid nanoparticle; PDI, polydispersity index; SLN, solid lipid nanoparticle.

Figure 4 TEM images of (A) a single BO-SLN/CM and (B) a crowd of BO-SLN/CM.

Abbreviations: BO-SLN/CM, borneol-modified chemically solid lipid nanoparticle; TEM, transmission electron microscopy.

Figure 5 (A) The MTT curve evaluating the cytotoxicity, (B) the uptake curve by HBMECs, (C) the Papp value curve evaluating the transport ability of BBB, and (D) the TEER curve of in vitro model of three kinds of SLNs.

Abbreviations: BBB, blood–brain barrier; BO-SLN/CM, borneol-modified chemically solid lipid nanoparticle; BO-SLN/PM, borneol-modified physically solid lipid nanoparticle; HBMEC, human brain microvascular endothelial cells; SLN, solid lipid nanoparticle; TEER, transepithelial electrical resistance.

Figure 6 TEM image of (A) normal, (B) treated with BO-SLN/CM, and (C) treated with fresh DMEM in vitro BBB model.

Abbreviations: BBB, blood–brain model; BO-SLN/CM, borneol-modified chemically solid lipid nanoparticle; DMEM, Dulbecco’s Modified Eagle’s Medium; TEM, transmission electron microscopy.

Figure 7 In vivo images of the (A) control group, (B) BO-SLN/CM group, (C) BO-SLN/PM group, and (D) SLN group, and (E) the fluorescence intensity curve of the in vivo imaging system.

Abbreviations: BO-SLN/CM, borneol-modified chemically solid lipid nanoparticle; BO-SLN/PM, borneol-modified physically solid lipid nanoparticle; SLN, solid lipid nanoparticle.