Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Abstract

Paclitaxel is a diterpenoid isolated from Taxus brevifolia . It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor ® EL (BASF, Ludwigshafen, Germany), which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm), which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly ( P < 0.01) reduced area under the concentration curve (AUC) 0–∞ (20.343 ± 9.119 μg · h · mL −1 vs 5.196 ± 1.426 μg · h · mL −1 ), greater clearance (2.050 ± 0.616 L · kg −1 · h −1 vs 0.556 ± 0.190 L · kg −1 · h −1 ), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC 0–∞ in liver, lung, and spleen (all P < 0.01), but not in heart or kidney.

VIP-targeted cytotoxic nanomedicine for breast cancer

“…Based on several other reports on biodistribution studies for various nanoparticulate drug systems [39–41], we conclude that biodistribution strongly depends on the carrier properties, such as size, composition, steric stabilization, in addition to the features of the drug itself, such as hydrophobicity and the mechanisms of its elimination. Nevertheless, in most cases drug delivery in a carrier system usually results in a favorable tumor accumulation.…”

Albumin-coated nanocrystals for carrier-free delivery of paclitaxel

“…Another type of PTX NC were produced by transforming an amorphous mixture of PTX and Pluronic F127 into crystalline particles and tested in two tumor models [13]. As NC were mostly distributed in the MPS organs leaving little drug in circulation [12, 14, 15], the NC were further modified with polyethylene glycol (PEG) by forming NC together with PEGylated PTX [16] or a crosslinkable polymeric amphiphile containing PEG [17]. Recently, iron-tannic acid complex was used to coat PTX nanoassemblies with an intention to reduce their MPS uptake [18].…”

Gene transfer to rat cerebral cortex mediated by polysorbate 80 and poloxamer 188 nonionic surfactant vesicles

“…Considering the recently shown promising results of cationic niosomes to transfect stem cells 17 and neurons in both brain and retina, 18 , 28 and the reports on literature that highlights the benefits of combining two surfactants in the same formulation, 22 , 23 we explored in the present manuscript, the impact of combining P and P80 nonionic surfactants in the same niosome gene-delivery system based on the cationic lipid DTPA.…”

“… 20 , 21 In addition, other reports in the literature highlight the advantage of combining two surfactants in the same formulation. 22 , 23 Particle size, polydispersity index (PDI), and zeta potential (ZP) of both niosomes were analyzed for comparison purposes. When the pCMS-EGFP plasmid was added at different cationic lipid/DNA ratios (w/w), the resulted nioplexes were physicochemically analyzed.…”