Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Figures & data

Figure 1 ¹H NMR spectra of stearic acid–grafted chitosan (CS-SA) conjugate.

Table 1 Characteristics of CS-SA micelles and DOX loaded CS-SA micelles

Micelles	dn (nm)	PI	ζ (mV)	EE (%)	DL (%)
CS-SA	22 ± 0.98	0.247 ± 0.025	36.4 ± 0.71
CS-SA/DOX	55.4 ± 4.95	0.298 ± 0.037	36.5 ± 1.1	81.23	10.65

Note: Data represent the mean ± standard deviation (n = 3).

Abbreviations: CS-SA/DOX, doxorubicin-loaded stearic acid–grafted chitosan; d_n, number average diameter; PI, polydispersity index of the diameter; ζ, zeta potential; EE, drug entrapment efficiency; DL, drug loading content.

Figure 2 Fluorescence intensity ratio of I₁/I₃ plotted against logarithm of stearic acid–grafted chitosan (CS-SA) concentration (A); transmission electron microscopy images of CS-SA micelles (B); doxorubicin loaded CS-SA micelles (C).

Figure 3 Fluorescence images of bEnd.3 after incubation with fluorescein isothiocyanate–labeled stearic acid–grafted chitosan micelles for 0.5, 1, 6, and 8 hours.

Figure 4 In vitro release profiles of doxorubicin (DOX)-loaded stearic acid–grafted chitosan (CS-SA) micelles in phosphate-buffered saline (pH 7.2).

Figure 5 (A–E) In vivo images of stearic acid–grafted chitosan/DiR. Images A–D were taken within 30 minutes after injection; E is ex vivo brain at 30 minutes after injection, compared with blank brain.

Figure 6 Brain distribution after injection of doxorubicin-loaded stearic acid–grafted chitosan at a dose of 2.5 mg/kg (equivalent of doxorubicin).

Note: Data represent the mean ± standard deviation. n = 3.

Table 2 Pharmacokinetic parameters in rat after intravenous administration of CS-SA/DOX and DOX · HCl

Kinetic parameter	DOX · HCl	CS-SA/DOX
AUC (0–t)	0.326 ± 0.025	0.969 ± 0.108
MRT (0–t)	1.705 ± 0.072	0.909 ± 0.174
CLz	0.656 ± 0.409	1.005 ± 0.13
Vz	12.59 ± 0.971	1.266 ± 0.246
Cmax	0.293 ± 0.074	1.344 ± 0.214

Abbreviations: CS-SA/DOX, doxorubicin-loaded stearic acid–grafted chitosan; HCl, hydrochloride; AUC, area under curve; MRT, mean retention time.

Figure 7 Plasma concentration versus time profiles of doxorubicin (DOX) following intravenous injection of DOX-loaded stearic acid–grafted chitosan (CS-SA/DOX) and DOX · hydrochloride (DOX HCL), both at a dose of 1 mg/kg (equivalent of DOX).

Note: Data represent the mean ± standard deviation. n = 5.

Figure 8 Tissue distribution at 0.5 and 2 hours after intravenous injection of doxorubicin-loaded stearic acid–grafted chitosan (CS-SA/DOX) and DOX · hydrochloride (DOX · HCl).

Note: Data represent the mean ± standard deviation. n = 3.