Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-β-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection

Figures & data

Table 1 Composition of PTX-loaded SLNs or PTX-loaded SLNs modified with HPCD

(Unit: mg)	PTX	Stearic acid	Lecithin	Poloxamer 188	Mannitol	HPCD
PS	5	100	75	75	100	–
PSC	5	100	75	75	–	400

Notes: The particle size of PS was 302.10±11.69 nm and that of PSC was 251.40±12.0 nm. And, the polydispersity of PS was 0.251±0.008 and that of PSC was 0.264±0.013.

Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; PS, PTX-loaded SLNs; HPCD, 2-hydroxypropyl-β-cyclodextrin; PSC, PTX-loaded SLNs modified using HPCD.

Figure 1 Cell proliferation of PTX-loaded SLNs (A) and PTX-loaded SLNs modified with HPCD (B) at 5 µM or 10 µM PTX concentration for 24 hours, 48 hours, or 72 hours incubation by MTT assay (n=3, mean ± SD). *P<0.05; **P<0.01.

Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Figure 2 Cellular uptake into MCF-7 cells treated with Nile red solution, Nile red-loaded SLNs, or Nile red-loaded SLNs modified with HPCD for 2 hours or 8 hours of incubation.

Notes: (A) Nile red solution for 2 hours, (B) Nile red solution for 8 hours, (C) Nile red-loaded SLNs for 2 hours, (D) Nile red-loaded SLNs for 8 hours, (E) Nile red-loaded SLNs modified with HPCD for 2 hours, (F) Nile red-loaded SLNs modified with HPCD for 8 hours.

Abbreviations: SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Figure 3 Apoptotic assay in MCF-7 cells treated with PTX solution, PTX-loaded SLNs, or PTX-loaded SLNs modified with HPCD corresponding 10 µM of PTX for 2 hours or 8 hours of incubation.

Notes: (A) PTX solution for 2 hours, (B) PTX solution for 8 hours, (C) PTX-loaded SLNs for 2 hours; (D) PTX-loaded SLNs for 8 hours, (E) PTX-loaded SLNs modified with HPCD for 2 hours, (F) PTX-loaded SLNs modified with HPCD for 8 hours.

Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Table 2 The pharmacokinetic parameters observed in rats after intravenous injection of 5 mg/kg dose of PTX solution, PTX-loaded SLNs or PTX-loaded SLNs modified with HPCD. The results represent the mean ± SD of three rats

	AUC0–∞ µg·h/mL)a	t1/2β (h)b	CL (L/h/kg)c
PTX solution	2.57±0.33	0.45±0.07	1.75±0.20
PS	3.31±0.34	0.66±0.10	1.35±0.18
PSC	5.07±0.68*	1.03±0.17*	0.99±0.13*

Notes:

a Area under the plasma concentration-time curve.

b Elimination half time.

c Total body clearance.

* P<0.05 compared with PTX solution.

Abbreviations: AUC, area under the curve; CL, clearance; PTX, Paclitaxel; PS, PTX-loaded SLNs; PSC, PTX-loaded SLNs modified using HPCD; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Figure 4 The concentration of PTX levels in rat plasma after intravenous injection of 5 mg/kg dose of PTX solution, PTX-loaded SLNs (PS) or PTX-loaded SLNs modified with HPCD (PSC).

Note: Each point represents the mean ± SD of three rats per time point.

Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Figure 5 The normalized kidney weight (A) and serum creatinine level (B) of intravenous injection with PTX solution, PTX-loaded SLNs (PS), or PTX-loaded SLNs modified with HPCD (PSC) after 8 hours of intravenous injection

Notes: n=3, mean ± SD. *P<0.05 compared with control.

Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Figure 6 The effect of PTX-loaded SLNs modified with HPCD on tumor volume and body weight.

Notes: The changes of tumor volumes (A) and body weight (B) according to the administration of saline, PTX solution, or PTX-loaded SLNs modified with HPCD (PSC) (n=3, mean ± SD).

Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.