Multidrug delivery system based on polysaccharide nanocomplexes for controlled delivery of a combination of chemotherapeutics

Antonio Di Martino, Kadir Ozaltin, Marina E. Trusova, Pavel S. Postnikov, Vladimir Sedlarik

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Development of delivery systems able to hold and release a combination of bioactive compounds at the target site represents a strategy for improving the therapeutic outcomes and overcome the central issues in the multitherapeutic approach. A delivery system based on polysaccharides suitable for loading a combination of chemotherapeutic drugs, doxorubicin and 5-fluorouracil, at defined weight ratio and deliver them following a pH-dependent kinetics was developed. Nanocomplexes were prepared by polyelectrolytes complexation and characterised in terms of average dimension, morphology, drug content by dynamic light scattering, transmission and scanning microscope and UV–Vis spectroscopy, respectively. The complexes showed a spherical shape with the hydrodynamic diameter between 100 and 130 nm, positive ς-potential, high stability in physiological environment and up to 800 μg of drugs per mg loaded. Release studies demonstrate a pH-dependent trend with high control of the release rate for each compound. In vitro hemocompatibility and not cytotoxicity were observed. In vitro studies showed a significate reduction of the cell viability after contact with the dual-drug loaded complexes than the single-loaded and free-drug formulations demonstrating the synergic effect of the drugs and the advantages of using the complexes. The results show the potential application of the nanosystems for multiple-drug delivery in therapy.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalJournal of Drug Delivery Science and Technology
Volume50
DOIs
Publication statusPublished - 1 Apr 2019

Fingerprint

Polysaccharides
Pharmaceutical Preparations
Drug Compounding
Drug Combinations
Hydrodynamics
Fluorouracil
Doxorubicin
Spectrum Analysis
Cell Survival
Weights and Measures
Therapeutics
In Vitro Techniques

Keywords

  • 5-Fluorouracil
  • 5-Fluorouracil (PubChem CID: 3385)
  • Alginic acid
  • Chitosan
  • Chitosan (PubChem CID: 71853)
  • Combination therapy
  • Doxorubicin
  • Doxorubicin hydrochloride (PubChem CID: 443939)
  • Nanocomplexes
  • Polysaccharides

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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title = "Multidrug delivery system based on polysaccharide nanocomplexes for controlled delivery of a combination of chemotherapeutics",
abstract = "Development of delivery systems able to hold and release a combination of bioactive compounds at the target site represents a strategy for improving the therapeutic outcomes and overcome the central issues in the multitherapeutic approach. A delivery system based on polysaccharides suitable for loading a combination of chemotherapeutic drugs, doxorubicin and 5-fluorouracil, at defined weight ratio and deliver them following a pH-dependent kinetics was developed. Nanocomplexes were prepared by polyelectrolytes complexation and characterised in terms of average dimension, morphology, drug content by dynamic light scattering, transmission and scanning microscope and UV–Vis spectroscopy, respectively. The complexes showed a spherical shape with the hydrodynamic diameter between 100 and 130 nm, positive ς-potential, high stability in physiological environment and up to 800 μg of drugs per mg loaded. Release studies demonstrate a pH-dependent trend with high control of the release rate for each compound. In vitro hemocompatibility and not cytotoxicity were observed. In vitro studies showed a significate reduction of the cell viability after contact with the dual-drug loaded complexes than the single-loaded and free-drug formulations demonstrating the synergic effect of the drugs and the advantages of using the complexes. The results show the potential application of the nanosystems for multiple-drug delivery in therapy.",
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AU - Sedlarik, Vladimir

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AB - Development of delivery systems able to hold and release a combination of bioactive compounds at the target site represents a strategy for improving the therapeutic outcomes and overcome the central issues in the multitherapeutic approach. A delivery system based on polysaccharides suitable for loading a combination of chemotherapeutic drugs, doxorubicin and 5-fluorouracil, at defined weight ratio and deliver them following a pH-dependent kinetics was developed. Nanocomplexes were prepared by polyelectrolytes complexation and characterised in terms of average dimension, morphology, drug content by dynamic light scattering, transmission and scanning microscope and UV–Vis spectroscopy, respectively. The complexes showed a spherical shape with the hydrodynamic diameter between 100 and 130 nm, positive ς-potential, high stability in physiological environment and up to 800 μg of drugs per mg loaded. Release studies demonstrate a pH-dependent trend with high control of the release rate for each compound. In vitro hemocompatibility and not cytotoxicity were observed. In vitro studies showed a significate reduction of the cell viability after contact with the dual-drug loaded complexes than the single-loaded and free-drug formulations demonstrating the synergic effect of the drugs and the advantages of using the complexes. The results show the potential application of the nanosystems for multiple-drug delivery in therapy.

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