Formulation, Characterization and Hypersensitivity Evaluation of an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex

Abstract

The objective of this paper was to develop a novel Cremophor-free, autoclave stable, intravenous emulsion for paclitaxel (PACE). A paclitaxel-cholesterol complex was used as the drug carrier to improve the solubility of paclitaxel in the oil phase of emulsions. The complex and PACE were prepared by rotary evaporation and highpressure homogenization, respectively. Effects of oil phases, emulsifiers and pH values on the characteristics of PACE were investigated. PACE was characterized with regard to its appearance, morphology, osmolality, pH value, particle size, zeta potential, encapsulation efficiency and stability. Hypersensitivity was evaluated by guinea pig hypersensitivity reaction. The final formulation was composed of the complex, soybean oil, mediumchain triglyceridel, soybean lecithin, poloxamer 188 and glycerol. The resulting PACE had an encapsulation efficiency of 97.3% with a particle size of 135 nm and a zeta potential of ؊38.3 mV. Osmolality and pH of the formulation were 383 mOsmol/kg and 4.5, respectively. The formulation survived autoclaving at 115°C for 30 min and remained stable for at least 12 months at 6°C. PACE also exhibited a better tolerance than an equal dose of Cremophor-based paclitaxel injection in guinea pigs, as no obvious hypersensitivity reaction was observed. These results suggested that PACE has a great potential for industrial-scale production and clinical applications.

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

“…17,21,33,35,36 In our previous study, a novel lipid Emul resembling the structure of LDL, which is composed of a PTX-CH complex surrounded by a phospholipid monolayer, was prepared and the in vitro and in vivo antitumor efficacy evaluated in a TNBC model. 26,27 The resulting lipid PTX-CH Emul exhibited superior in vitro antitumor efficacy, higher specificity …”

“…26,27 cell lines and cell culture H9c2 (2-1), MDA-MB-231, and MCF7 were supplied by the Cell Resource Center, Peking Union Medical College (Beijing, People's Republic of China). H9c2 (2-1) and MCF7 cells were cultured in Dulbecco's Modified Eagle's Medium supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 µg/mL streptomycin.…”

“…27 The resulting lipid emulsion (PTX-CH Emul) exhibits an ideal particle size, high drug-loading capability, high drugencapsulation efficiency, and excellent stability (12 months at 6°C). 26 Furthermore, PTX-CH Emul shows superior in vitro antitumor efficacy, higher specificity and efficiency in intratumoral accumulation, better safety profiles, and superior antitumor efficacy in vivo against TNBC compared to the conventional PTX Emul and Taxol. 27 Although PTX-CH Emul shows great potential as a drug carrier for PTX in clinical applications involving TNBC therapy, 26,27 intracellular trafficking and its underlying mechanisms have not been investigated.…”

“…26 Furthermore, PTX-CH Emul shows superior in vitro antitumor efficacy, higher specificity and efficiency in intratumoral accumulation, better safety profiles, and superior antitumor efficacy in vivo against TNBC compared to the conventional PTX Emul and Taxol. 27 Although PTX-CH Emul shows great potential as a drug carrier for PTX in clinical applications involving TNBC therapy, 26,27 intracellular trafficking and its underlying mechanisms have not been investigated. In order to improve the therapeutic potential of PTX-CH Emul for the treatment of TNBC further, it is important to make a comparative evaluation of the antineoplastic effects of PTX-CH Emul on TNBC and non-TNBC cells.…”

“…Alternatively, a novel lipid emulsion, which was composed of a PTX-CH complex surrounded by a phospholipid monolayer, was developed in our previous work ( Figure 1). 26 Compared with the tumor-targeting LDE-PTX loaded with PTX and cholesteryl ester reported previously, 21 substitution of the PTX-CH complex for PTX and cholesteryl ester of LDE-PTX has the following advantages: the PTX-CH complex not only greatly improves PTX solubility in the oil phase but can also function as a component of LDL-CH. 27 The resulting lipid emulsion (PTX-CH Emul) exhibits an ideal particle size, high drug-loading capability, high drugencapsulation efficiency, and excellent stability (12 months at 6°C).…”