Original Article
Improving paclitaxel pharmacokinetics by using tumor-specific mesoporous silica nanoparticles with intraperitoneal delivery

https://doi.org/10.1016/j.nano.2016.04.013Get rights and content

Abstract

Mesoporous silica nanoparticles (MSNs) containing paclitaxel for intraperitoneal (i.p.) delivery were developed to exploit the tumor specific accumulation of these nanocarriers after i.p. injection and the slow release of paclitaxel from the MSNs. A 3.5-fold increase in tumor cellular drug uptake was observed for the paclitaxel-loaded MSNs compared with free paclitaxel. An in vivo study using xenograft mice bearing peritoneal human pancreatic carcinoma MIA PaCa-2 demonstrated that the MSN-paclitaxel formulation, compared to free paclitaxel, exhibited a 3.2-fold increase in peritoneal cavity residence time, slower absorption into the systemic circulation with one third systemic exposure, but a 6.5-fold increase in peritoneal tumor accumulation. Tissue distribution imaging showed significantly greater accumulation of fluorescent MSNs in tumor tissues compared to other peritoneal tissues. In conclusion, intraperitoneal administration of drug-containing MSNs was effective at reducing systemic exposure and increasing the peritoneal tumor accumulation of paclitaxel.

Graphical Abstract

Mesoporous silica nanoparticles (MSNs) containing paclitaxel facilitated its selective tumor accumulation and increased retention time both in the peritoneal cavity and in the systemic circulation. The pharmacokinetics and distribution profiles of paclitaxel were improved for the effective treatment for peritoneal cancers.

  1. Download : Download high-res image (107KB)
  2. Download : Download full-size image

Section snippets

Materials

Paclitaxel (PTX), cephalomannine, rhodamine, mesoporous silica type MCM-41, tetraethyl orthosilicate (TEOS), trypsin-EDTA solution, Triton X-100, and Dulbecco's modified Eagle's medium (DMEM) were purchased from Sigma (St. Louis, MO, USA). 1,1′-Dioctadecyl-3 ,3 ,3′,3′-tetramethylindotricarbocyanine iodide (DiR), Fetal Bovine Serum (FBS), and penicillin–streptomycin solution were purchased from Biotium (Invitrogen, USA). All other chemicals were of analytical grade.

Synthesis of mesoporous silica nanoparticles

MSNs were synthesized as

Synthesis and characterization of mesoporous silica nanoparticles (MSNs)

Transmission electron microscopy analysis showed that the synthesized MSNs were spherical in shape and approximately 100 nm in diameter with pores in hexagonal arrays (Figure 1). The pore size of the synthesized MSNs is 2.3 ± 0.3 nm, with narrow distribution. These MSNs tend to aggregate and settle in aqueous due to high density of the silica material (~ 2 g/cm3) and the hydrophobic surface. After sonication, the particles can be homogenously suspended. The measured particle size using dynamic light

Discussion

The present study was designed to demonstrate the positive impact of MSN on the disposition of paclitaxel in IP chemotherapy. According to our prior report, the MSNs accumulated preferentially in tumors with limited exposure to other tissues after IP delivery of radioactive MSNs.11 We report here that paclitaxel carried by MSNs exhibited a sustained release profile from MSNs compared to paclitaxel only. The relatively slow and sustained release from PTX-loaded MSNs may be ascribed to the strong

References (28)

  • D.K. Armstrong et al.

    Intraperitoneal cisplatin and paclitaxel in ovarian cancer

    N Engl J Med

    (2006)
  • J. Szebeni et al.

    Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study

    J Natl Cancer Inst

    (1998)
  • S.K. Williamson et al.

    A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax®) in patients with peritoneal malignancies

    Cancer Chemother Pharmacol

    (2015)
  • Hongye Yea et al.

    Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models

    J Control Release

    (2015)
  • Cited by (50)

    • Engineering biodegradable periodic mesoporous functionalized-organosilica nanocarriers for efficient paclitaxel delivery

      2023, Colloids and Surfaces A: Physicochemical and Engineering Aspects
      Citation Excerpt :

      Mesoporous silica nanoparticles (MSN) have been widely utilized as a promising drug delivery system for various biomedical applications owing to their controllable morphology and particle size, ease of functional surface modification, large surface area, and tunable pore size which contribute to the high loading capacity and high stability of drugs [1].

    • Nanocarriers for targeted drug delivery

      2021, Journal of Drug Delivery Science and Technology
      Citation Excerpt :

      These early tests give solid confirmation that MSNs are promising candidates for enhanced tumor treatment and that they can diminish reactions for normal tissues and cells. Table 2 enlists applications of various types of NPs [108–120]. Clinically used nanomedicines and those in various trial phases are given in Table 3.

    View all citing articles on Scopus

    The work is supported by National Cancer Institute (NCI)R03CA184394 and the Research Scholar Grant, RSG-15-011-01-CDD from the American Cancer Society.

    View full text