ArticlePharmaceutical research2016
Synthesis and In Vitro Evaluation of Polyethylene Glycol-Paclitaxel Conjugates for Lung Cancer Therapy.
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 20 citations in OpenAlex.
- Polyethylene Glycol-Based Polymer-Drug Conjugates: Novel Design and Synthesis Strategies for Enhanced Therapeutic Efficacy and Targeted Drug Delivery.Applied biochemistry and biotechnology · 2024Review
- Functionalized Liposome and Albumin-Based Systems as Carriers for Poorly Water-Soluble Anticancer Drugs: An Updated Review.Biomedicines · 2022Review
- Self-assembled and pH-responsive polymeric nanomicelles impart effective delivery of paclitaxel to cancer cells.RSC advances · 2021Article
- Rational Design of Polyglutamic Acid Delivering an Optimized Combination of Drugs Targeting Mutated BRAF and MEK in Melanoma.Advanced therapeutics · 2020Article
- Polymer-Drug Conjugate, a Potential Therapeutic to Combat Breast and Lung Cancer.Pharmaceutics · 2020Review
- Clinical developments of antitumor polymer therapeutics.RSC advances · 2019Review
- Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug.Medicina (Kaunas, Lithuania) · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePulmonary drug delivery is considered an attractive route of drug administration for lung cancer chemotherapy. However, fast clearance mechanisms result in short residence time of small molecule drugs in the lung. Therefore, achieving a sustained presence of chemotherapeutics in the lung is very challenging. In this study, we synthesized two different polyethylene glycol-paclitaxel ester conjugates with molecular weights of 6 and 20 kDa in order to achieve sustained release of paclitaxel in the lung.
methodsOne structure was synthesized with azide linker using "click" chemistry and the other structure was synthesized with a succinic spacer. The physicochemical and biological properties of the conjugates were characterized in vitro.
resultsConjugation to polyethylene glycol improved the solubility of paclitaxel by up to four orders of magnitude. The conjugates showed good stability in phosphate buffer saline pH 6.9 (half-life ≥72 h) and in bronchoalveolar lavage (half-life of 3 to 9 h) at both molecular weights, but hydrolyzed quickly in mouse serum (half-life of 1 to 3 h). The conjugates showed cytotoxicity to B16-F10 melanoma cells and LL/2 Lewis lung cancer cells but less than free paclitaxel or Taxol, the commercial paclitaxel formulation.
conclusionsThese properties imply that the conjugates have the potential to retain paclitaxel in the lung for a prolonged duration and to sustain its release locally for a better efficacy.
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