Hydroxypropylcellulose-flurbiprofen conjugates: design, characterization, anti-inflammatory activity and enhanced...

Area of Science:

• Polymer Chemistry
• Medicinal Chemistry
• Drug Delivery

Background:

• Flurbiprofen (FLB) is a nonsteroidal anti-inflammatory drug (NSAID) with limitations in bioavailability.
• Macromolecular prodrugs offer a strategy to improve drug pharmacokinetics and efficacy.
• Cellulose ethers like hydroxypropylcellulose (HPC) are biocompatible polymers suitable for drug conjugation.

Purpose of the Study:

• To synthesize novel macromolecular prodrugs (MPDs) of flurbiprofen (FLB) by conjugating it to hydroxypropylcellulose (HPC).
• To characterize the synthesized HPC-FLB conjugates and evaluate their pharmacokinetic properties and anti-inflammatory activity.

Main Methods:

• Flurbiprofen activation using carbonyldiimidazole (CDI) to form an intermediate imidazolide.
• Reaction of the activated flurbiprofen with hydroxypropylcellulose in DMAc solvent at 80°C for 24 hours.
• Characterization of the resulting conjugates using FTIR, UV, and NMR spectroscopy.
• Pharmacokinetic studies to determine half-life (t1/2) and time to maximum concentration (tmax).

Main Results:

• Successful synthesis of HPC-FLB conjugates with a moderate to high degree of substitution (DS: 0.35-1.3) and good yields (70-82%).
• Spectroscopic analyses confirmed the successful conjugation of FLB onto the HPC backbone.
• Pharmacokinetic studies revealed significantly increased t1/2 and tmax for FLB from HPC-FLB conjugates compared to free FLB, indicating enhanced bioavailability.
• The HPC-FLB conjugate exhibited notable anti-inflammatory activity.

Conclusions:

• Novel macromolecular prodrugs of flurbiprofen based on hydroxypropylcellulose have been successfully synthesized and characterized.
• The developed HPC-FLB conjugates demonstrate improved pharmacokinetic profiles, including enhanced bioavailability.
• These conjugates also possess significant anti-inflammatory properties, suggesting their potential as effective therapeutic agents.