Study on the thermal stability of nab-paclitaxel during hyperthermic intraperitoneal chemotherapy

Abstract

Background: Albumin-bound paclitaxel (nab-paclitaxel), as a special targeted preparation of paclitaxel, has the advantages of good curative effect and less side effects in anti-tumor therapy. The existence of the plasma-peritoneal barrier and insufficient blood supply make intravenous drugs hard to reach the peritoneum, while hyperthermic intraperitoneal chemotherapy can solve the difficulty. And compared with systemic medications, HIPEC can also give higher concentrations of chemotherapy drugs in the abdominal cavity, while ensuring lower systemic toxicity. However, at present, there is no relevant report on the clinical study of nab-paclitaxel during intraperitoneal hyperthermic chemotherapy, and its stability under special temperature conditions has not been reported either.

Methods: In this study, We examined three batches of albumin-bound paclitaxel dissolved in saline at different temperatures (25 °C, 37 °C, 41 °C, 42 °C and 43 °C) for the changes of human serum albumin content, human serum albumin polymer content, related substance content, in-vitro release rate, paclitaxel binding rate and paclitaxel content at different temperatures.

Results: Our results demonstrated that the indicators including human serum albumin content, human serum albumin polymer content, in-vitro release rate, paclitaxel binding rate and paclitaxel content were stable to the several temperatures, except that Taxane (0.1%) and other individual impurities in the determination of related substance content fluctuated comparatively widely with the change of temperature. In addition, only Taxane (0.1%) and 7-Epitaxol (1%) were detected.

Conclusions: Overall, albumin-bound paclitaxel is relatively stable to different temperatures (25 °C, 37 °C, 41 °C, 42 °C and 43 °C). This study will lay a foundation for further studies on the albumin-bound paclitaxel during hyperthermic intraperitoneal chemotherapy.

Keywords: Albumin-bound paclitaxel; Hyperthermic intraperitoneal chemotherapy; Temperature; Thermal stability.

Fig. 1

The experimental design with timeline

Fig. 2

The results of weight changes of three batches of albumin-bound paclitaxel at different temperatures

Fig. 3

Chromatograms of human albumin reference substance (A) and albumin-bound paclitaxel (B)

Fig. 4

The results of content changes of three batches of polymer of albumin-bound paclitaxel at different temperatures

Fig. 5

Chromatograms of Polymer (1), Unknown impurities (2), Dimer (3) and Monomer (4)

Fig. 6

The results of content changes of three batches of taxane of albumin-bound paclitaxel at different temperatures

Fig. 7

The results of content changes of three batches of 7-Epitaxol of albumin-bound paclitaxel at different temperatures

Fig. 8

The results of content changes of three batches of other individual impurities of albumin-bound paclitaxel at different temperatures

Fig. 9

Chromatograms of system suitability solution A (A): 2-Baccatin III (2), 1-(2R,3S)-N-benzoyl-3-phenylisoserine methyl ester (3), 5-Paclitaxel (5), 10-Deacetyl-6-7-epipaclitaxel (6), 7–7-Epipaclitaxel (7), system suitability solution B (B), system suitability solution C (C) and albumin-bound paclitaxel (D): 1–20-Taxane (3), 3-Paclitaxel (4), 4–7-Epipaclitaxel (5)

Fig. 10

The results of in-vitro release rate of three batches of albumin-bound paclitaxel at different temperatures

Fig. 11

Chromatograms of control solution (A) and test solution (B)

Fig. 12

The results of binding rate of three batches of albumin-bound paclitaxel at different temperatures

Fig. 13

The content results of paclitaxel of three batches of albumin-bound paclitaxel at different temperatures

Fig. 14

Chromatograms of control solution (A) and test solution (B)

Fig. 15

Solvent chromatogram (A) and the chromatogram of system suitability solution (B): 1-Cephalomannine (1), 2-Paclitaxel (2)