Novel polymeric prodrugs were synthesized by mechanochemical solid-state copolymerization of hydroxyethylcellulose and the methacryloyloxy derivative of 5-fluorouracil (5-FU). Copolymerization was about 94% complete after 4 h, and the polymeric prodrug was quantitatively obtained after 14 h of reaction. The number average molecular weight (Mn) and polydispersity (H) of the polymeric prodrug were 39000 g/mol and 6.20, respectively. Mechanical fracturing of the polymer in a stainless steel twin-shell blender improved these properties (Mn=16000 g/mol and H=1.94). 5-FU was sustainably released from the polymeric prodrugs, and the rate was not affected by the molecular weight or molecular weight distribution of the prodrug under the experimental conditions used. These results suggest that novel polymeric prodrugs composed of a polysaccharide and a synthetic polymer can be fabricated by mechanochemical solid-state copolymerization under anaerobic conditions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1248/cpb.c15-00497 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hypoxia-tolerant polymeric photosensitizer prodrug for cancer photo-immunotherapy.
Nat Commun
January 2025
National Engineering Research Centre for Nanomedicine, College of Life Science and Technology, Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, PR China.
Although photodynamic immunotherapy represents a promising therapeutic approach against malignant tumors, its efficacy is often hampered by the hypoxia and immunosuppressive conditions within the tumor microenvironment (TME) following photodynamic therapy (PDT). In this study, we report the design guidelines towards efficient Type-I semiconducting polymer photosensitizer and modify the best-performing polymer into a hypoxia-tolerant polymeric photosensitizer prodrug (HTPS) for cancer photo-immunotherapy. HTPS not only performs Type-I PDT process to partially overcome the limitation of hypoxic tumors in PDT by recycling oxygen but also specifically releases a Signal Transducer and Activator of Transcription-3 (STAT3) inhibitor (Niclosamide) in response to a cancer biomarker in the TME.
View Article and Find Full Text PDFImproved Control of Triple-Negative Breast Cancer Tumor and Metastasis with a pH-Sensitive Hyaluronic Acid Nanocarrier for Doxorubicin Delivery.
ACS Biomater Sci Eng
December 2024
Future Industries Institute, University of South Australia, Mawson Lakes, South Australia 5095, Australia.
Polymer based nanoformulations offer substantial prospects for efficacious chemotherapy delivery. Here, we developed a pH-responsive polymeric nanoparticle based on acidosis-triggered breakdown of boronic ester linkers. A biocompatible hyaluronic acid (HA) matrix served as a substrate for carrying a doxorubicin (DOX) prodrug which also possesses natural affinity for CD44 cells.
View Article and Find Full Text PDFBicontinuous Nanoparticles from Spontaneous Self-Assembly of Block Copolymer Prodrug in Aqueous Medium for Potential Cancer Therapy.
ACS Macro Lett
December 2024
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal 721302, India.
Despite having several advantages, bicontinuously structured polymeric nanoparticles (BSPNPs) are far less explored in the field of controlled drug delivery owing to the requirement of complex precursor copolymers and the associated multistep synthetic procedures. In this work, we report the synthesis of a redox-sensitive diblock copolymer (P1), which was subsequently utilized to prepare doxorubicin (DOX) containing a pH-labile prodrug (P2). P1 and P2 spontaneously self-assembled in aqueous media above their critical aggregation concentration, forming micellar nanoparticles with rare bicontinuous morphology that promotes loading of both hydrophobic and hydrophilic cargoes in different compartments.
View Article and Find Full Text PDFZero-Order Kinetics Release of Lamivudine from Layer-by-Layer Coated Macromolecular Prodrug Particles.
Int J Mol Sci
December 2024
Department of Physical Chemistry and Biophysics, Pharmaceutical Faculty, Wroclaw Medical University, Borowska 211, 50-556 Wrocław, Poland.
To reduce the risk of side effects and enhance therapeutic efficiency, drug delivery systems that offer precise control over active ingredient release while minimizing burst effects are considered advantageous. In this study, a novel approach for the controlled release of lamivudine (LV) was explored through the fabrication of polyelectrolyte-coated microparticles. LV was covalently attached to poly(ε-caprolactone) via ring-opening polymerization, resulting in a macromolecular prodrug (LV-PCL) with a hydrolytic release mechanism.
View Article and Find Full Text PDFNanoparticle-enabled In Situ drug potency activation for enhanced tumor-specific therapy.
Eur J Pharm Sci
December 2024
Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou 215123, China; State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200438, China. Electronic address:
Cancer treatment faces significant challenges including inadequate tumor specificity, drug resistance, and severe side effects, often resulting in unsatisfactory patient outcomes. Nanomedicines offer a transformative platform for tumor-targeted drug delivery and antitumor potency activation, providing an indispensable strategy for overcoming the severe damage to normal tissues caused by the inherent "always-on" cytotoxicity of conventional therapeutic agents. This review focuses on the emerging concept of "nanoparticle-enabled in situ drug potency activation", where inactive or minimally toxic agents are selectively activated within tumors to enhance the therapeutic efficacy and minimize the adverse effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!