Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings

Figures & data

Figure 1 Structure, molecular formula, and molecular weight of CLA-PTX.

Notes: Molecular formula of CLA-PTX C₆₅H₈₁NO₁₅. Molecular weight of CLA-PTX 1116.

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.

Figure 2 Typical droplet size and distribution of the CLA-PTX microemulsion (A) and transmission electron micrograph of CLA-PTX microemulsion (B).

Note: Bar 200 nm.

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.

Table 1 Droplet size, polydispersity index, and zeta potential of CLA-PTX microemulsion (n = 3)

	Droplet size (nm)	Polydispersity	Zeta potential (mV)
CLA-PTX microemulsion	176.3 ± 0.8	0.294 ± 0.024	−21.31 ± 4.61

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.

Table 2 Cytotoxicity of various CLA-PTX formulations for C6 cells (n = 3)

CLA-PTX formulations	IC50 (μM)
Free PTX	2.11 ± 1.03
CLA-PTX solution	2.47 ± 1.16
CLA-PTX microemulsion	1.61 ± 0.83

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.

Figure 3 In vivo antitumor activity of CLA-PTX microemulsion in C6 tumor-bearing nude mice.

Notes: Balb/C nude mice were inoculated subcutaneously with C6 cells and treated with a 5% glucose infusion, Taxol^® (15 mg/kg, intravenously, every 3 days for three doses), or CLA-PTX microemulsion 20 mg/kg (equimolar with 15 mg/kg of paclitaxel), intravenously every 3 days for three doses, respectively. The control group was given the 5% glucose infusion. Formulations were given intravenously via the tail vein. Throughout the study, the mice were weighed and tumors were measured with calipers every two days. **P < 0.01 versus 5% glucose infusion as control; ^##P < 0.01 versus Taxol.

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.

Figure 4 In vivo antitumor activity of CLA-PTX microemulsion in C6 brain tumor-bearing rats.

Notes: Tumor weight is shown at the time of sacrifice, 20 days post-inoculation. Formulations were administered intravenously via the tail vein at days 7, 10, and 13 after tumor inoculation. Animals were sacrificed on day 20 post-tumor inoculation (n = 10). Control group, 5% glucose infusion; Taxol^® treatment group, at a dose of 5 mg/kg; CLA-PTX microemulsion treatment group, at a dose of 6.67 mg/kg (equimolar with 5 mg/kg of paclitaxel). **P < 0.01 versus 5% glucose infusion as control; ^##P < 0.01 versus Taxol treatment group.

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.

Table 3 Tumor weight inhibition (%) of CLA-PTX microemulsion against control and Taxol^®

Groups	Dose	TWI (%) against control	TWI (%) against taxol
CLA-PTX microemulsion	6.67 mg/kg	61.1 ± 13.5	58.5 ± 14.4

Abbreviations: CLA-PTX, linoleic acid conjugated with paclitaxel; TWI, tumor weight inhibition.

Figure 5 Plasma concentration-time profiles of CLA-PTX after intravenous administration of CLA-PTX solution or CLA-PTX microemulsion at 6.67 mg/kg CLA-PTX in Sprague-Dawley rats.

Notes: Mean ± standard deviation, n = 5.

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.

Table 4 Main pharmacokinetic parameters of CLA-PTX after intravenous administration of CLA-PTX solution or CLA-PTX microemulsion at 6.67 mg/kg of CLA-PTX in Sprague-Dawley rats (n = 5)

Parameters	Units	CLA-PTX solution	CLA-PTX microemulsion
C0.5	μM	132.9 ± 7.0	68.5 ± 23.8**
AUCinf	Hours*μM	2296 ± 128	389 ± 148**
t1/2	Hours	59.6 ± 25.3	24.4 ± 5.6**
MRT	Hours	36.6 ± 2.5	18.9 ± 4.4**
Vss	L/kg	0.218 ± 0.084	0.619 ± 0.281**
Cl	mL/hour/kg	2.68 ± 0.669	16.8 ± 4.7**

Note:

** P < 0.01 versus CLA-PTX solution treatment group.

Abbreviations: AUC, area under the concentration-time curve; CLA-PTX, linoleic acid conjugated with paclitaxel; MRT, mean residence time.

Figure 6 Acute toxicity of CLA-PTX microemulsion (-■-) and CLA-PTX solution (-▲-) administered via the intravenous route.

Note: n = 10 per dose.

Abbreviation: CLA-PTX, linoleic acid conjugated with paclitaxel.