Structural parameters governing activity of Pluronic triblock copolymers in hyperthermia cancer therapy

Figures & data

Table I.  Pluronic information.

Pluronic	Formula^a	Mw (Da)^b	HLB^c	CMC (M)^d	CMC (wt%)
L31	EO2-PO16-EO2	1100	3.2	N/A
L35	EO11-PO16-EO11	1900	10	5.3 × 10^−3	1.007
L61	EO2-PO31-EO2	2000	2.0	1.1 × 10^−4	0.022
L44	EO10-PO23-EO10	2200	8	3.6 × 10^−3	0.792
L62	EO6-PO35-EO6	2500	4.0	4.0 × 10^−4	0.1
L81	EO3-PO43-EO3	2750	2.0	2.3 × 10^−5	0.0063
L64	EO13-PO30-EO13	2900	8.0	4.8 × 10^−4	0.14
L10	EO4-PO50-EO4	3200	2.0	N/A
L92	EO8-PO50-EO8	3650	4.0	8.8 × 10^−5	0.032
L121	EO5-PO68-EO5	4400	2.0	1.0 × 10^−6	0.0004
P85	EO26-PO40-EO26	4600	10	6.5 × 10^−5	0.03
P123	EO20-PO69-EO20	5750	6.0	4.4 × 10^−6	0.0025
F87	EO61-PO40-EO61	7700	24	9.1 × 10^−5	0.07

^a,^bInformation provided by the manufacturer; PO, propylene oxide; EO, ethylene oxide. Mw: molecular weight; Da: Dalton.

^cInformation calculated based on Mw of PO and EO; HLB: hydrophilic lipophilic balance.

^dCMC, critical micelle concentration; information was adapted from Batrakova et al.[39]. M: molar; wt%: weight percent.

Figure 1. Pluronic thermosensitising effects on DHD/K12/TRb cells in vitro after 20 min of Pluronic and hyperthermia (at 43°C) co-exposure. Pluronic concentrations are 2.5 mg/mL. Data presented as Mean ± SD (standard deviation, n = 3). *Significant difference compared to Pluronic only; ^†significant difference compared to untreated control (P < 0.05).

Figure 2. Dependence of Pluronic bioactivity on average molecular weight: (A) hydrophilic Pluronics; (B) hydrophobic Pluronics. Results are based on the dehydrogenase activity acquired with WST-1 assay. Data presented as Mean ± SD (standard deviation, n = 3).

Figure 3. Caspase 3/7 activity. Data are normalised by the cell counts: (A) 2 h after treatment; (B) 24 h after treatment. Data presented as Mean ± SD (standard deviation, n = 4). *Significant difference versus hyperthermia only; ^‡significant difference versus Pluronic only (P < 0.05).

Figure 4. Change in tumour volume relative to size before treatment in response to radiofrequency ablation with or without Pluronic L61. Data presented as Mean ± SD (standard deviation, n = 17). Portions of the error bars were omitted for presentation clarity. *Indicates statistically significant difference (P < 0.05).

Figure 5. Proportion of tumours showing shrinkage of <100% in volume. Estimation was done with Kaplan-Meier survival methods and the statistics were acquired with the Cox proportional hazards regression model (P = 0.03).

Figure 6. The four-group Pluronic copolymer grid based on Pluronic HLB and N_PO adapted from a previously published model [11]. Here the authors categorised the investigated Pluronic copolymers into four groups according to the HLB and N_PO numbers. According to their results, Group II polymers were the most effective in modulating P-glycoprotein, while polymers from Group I and III showed little effect.

Batrakova E, Lee S, Li S, Venne A, Alakhov V, Kabanov A. Fundamental relationships between the composition of Pluronic block copolymers and their hypersensitization effect in MDR cancer cells. Pharm Res 1999; 16: 1373–1379

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Batrakova EV, Li S, Alakhov VY, Miller DW, Kabanov AV. Optimal structure requirements for Pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells. J Pharmacol Exp Ther 2003; 304: 845–854

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