Development of PEGylated solid lipid nanoparticles of pentoxifylline for their beneficial pharmacological potential in pathological cardiac hypertrophy

Figures & data

Figure 1. Experimental protocol. PAAC, partial abdominal aortic constriction; PTX, pentoxifylline; PTX-SLN, solid lipid nanoparticles of pentoxifylline; SAC, sacrifice; BA, biochemical analysis.

Table I. Optimisation of formulation.

F. No	Homo. time	Homo. speed	Sonica. time	DSPE-PEG	Surfactant–lipid ratio	PTX	Particle size	PDI	EE%
F1	7	6000	3	NA	1:2	NA	1630 ± 15.7	0.422	NA
F2	7	6000	3	NA	1:3	NA	1550 ± 22.8	0.386	NA
F3	7	6000	3	NA	1:4	NA	1650 ± 55.67	0.396	NA
F4	7	6000	3	NA	1:3	NA	1500 ± 53.3	0.386	NA
F5	8	6000	3	NA	1:3	NA	1472 ± 33.3	0.376	NA
F6	9	6000	3	NA	1:3	NA	1480 ± 32.2	0.372	NA
F7	10	6000	3	NA	1:3	NA	1200 ± 44.2	0.369	NA
F8	11	6000	3	NA	1:3	NA	1410 ± 47.4	0.373	NA
F9	10	7000	3	NA	1:3	NA	920 ± 28.3	0.341	NA
F10	10	8000	3	NA	1:3	NA	824 ± 20.2	0.315	NA
F11	10	9000	3	NA	1:3	NA	1021 ± 32.1	0.310	NA
F12	10	8000	4	NA	1:3	NA	480 ± 17.3	0.283	NA
F13	10	8000	5	NA	1:3	NA	254 ± 11.2	0.271	NA
F14	10	8000	6	NA	1:3	NA	367 ± 16.8	0.294	NA
F15	10	8000	5	14	1:3	NA	260 ± 11.3	0.180	NA
F16	10	8000	5	28	1:3	NA	266 ± 7.5	0.169	NA
F17	10	8000	5	56	1:3	NA	347 ± 16.3	1.12	NA
F18	10	8000	5	28	1:3	10	379 ± 17.2	0.178	71.3 ± 4.5%
F19	10	8000	5	28	1:3	20	368 ± 10.07	0.166	91.9 ± 5.1%
F20	10	8000	5	28	1:3	30	390 ± 24.2	0.192	87.2 ± 4.0%
F21	10	8000	5	28	1:3	40	484 ± 23.3	0.177	81.3 ± 5.6%

EE%, entrapment efficiency; F, formulation; NA, not applicable; PDI, polydispersity index; PTX, pentoxifylline.

F2 represents optimization of surfactant:lipid ratio; F7 represents optimized homogenization time; F10 represents optimized homogenization speed; F13 represents optimized sonification time; F16 represents DSPE-PEG concentration; F19 represents optimized Drug Concentration.

Figure 2. Percentage cumulative release of pentoxifylline versus time curve.

Figure 3. Pharmacokinetic profile of pure drug and PEGylated SLNs of pentoxifylline. NANO-PTX, PEGylated nanoparticles of pentoxifylline; PTX, pentoxifylline.

Table II. Pharmacokinetic parameters of pentoxifylline-loaded SLNs compared to pure drug.

Pharmacokinetic parameters	Units	Pure drug (PTX)	Nanoparticles (PTX-SLNS)
Cmax	ng ml^−1	213	423
t½	h	1.25	8.34
% AUC	–	6.41	14.92
MRT	h	5.06	12.94

AUC, area under the curve; C_max, plasma maximum drug concentration; MRT, mean residence time; t_½, half-life.

Figure 4. Effect of pharmacological interventions on LVEDP. @p < 0.05 versus Sham control, *p < 0.05 versus PAAC control, #p < 0.05 versus PAAC + PTX (3 mg kg⁻¹). PAAC, partial abdominal aortic constriction; LVEDP, left ventricular end diastolic pressure; PTX, pentoxifylline, ENAL, enalapril; PTX + SLNs, nanoparticles of PTX.

Figure 5. Effect of pharmacological interventions on MABP. @p < 0.05 versus Sham control, *p < 0.05 versus PAAC control, #p < 0.05 versus PAAC + PTX (3 mg/kg). PAAC, partial abdominal aortic constriction; MABP, mean arterial blood pressure; PTX, pentoxifylline; ENAL, enalapril; PTX + SLNs, nanoparticles of pentoxifylline.

Figure 6. Effect of pharmacological interventions on LVW/BW in rats. @p < 0.05 versus Sham control, *p < 0.05 versus PAAC control, #p < 0.05 versus PAAC + PTX (3 mg kg⁻¹). PAAC, partial abdominal aortic constriction; LVW/BW, left ventricular weight/body weight; PTX, pentoxifylline; ENAL, enalapril; PTX + SLNs, nanoparticles of pentoxifylline.

Figure 7. Effect of pharmacological interventions on LVWT. @p < 0.05 versus Sham control, *p < 0.05 versus PAAC control, #p < 0.05 versus PAAC + PTX (3 mg kg⁻¹). PAAC, partial abdominal aortic constriction; LVWT, left ventricular wall thickness; PTX, pentoxifylline; ENAL, enalapril; PTX + SLNs, nanoparticles of Pentoxifylline.

Figure 8. Effect of Pharmacological interventions on left ventricular protein content. @p < 0.05 versus Sham control, *p < 0.05 versus PAAC control, #p < 0.05 versus PAAC + PTX (3 mg kg⁻¹). PAAC, partial abdominal aortic constriction, protein content expressed as mg protein in left ventricle to left ventricular weight in gram; PTX, pentoxifylline; ENAL, enalapril; PTX + SLNs, nanoparticles of pentoxifylline.

Figure 9. Effect of pharmacological interventions on left ventricular TNF-α level @p < 0.05 versus Sham control, *p < 0.05 versus PAAC control, #p < 0.05 versus PAAC + PTX (3 mg kg⁻¹). PAAC, partial abdominal aortic constriction; PTX, pentoxifylline; ENAL, enalapril; PTX + SLNs, nanoparticles of pentoxifylline.