A Silibinin-Poly(ε-Caprolactone) Conjugate as an Enhanced Anticancer Agent.

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Poly(ε-caprolactone) (PCL) is a widely used biodegradable polyester in drug delivery, typically incorporating drugs physically.
• Limited functional groups in PCL hinder covalent drug attachment, restricting conjugate development.
• Developing covalently bonded biopolyester-drug conjugates is crucial for improved drug loading and efficacy.

Purpose of the Study:

• To synthesize a covalent Silibinin-PCL conjugate (Sil-PCLHyd) using a facile two-step method.
• To achieve high drug loading capacity within the biopolyester matrix.
• To evaluate the cytotoxic effects of the novel conjugate on cancer cells.

Main Methods:

• Controlled hydrolysis of high molecular weight PCL to generate carboxylic end groups.
• Catalyzed esterification of PCL carboxylic end groups with Silibinin.
• Characterization using mass spectrometry, GPC, TGA, DSC, NMR, and UV-vis spectroscopy.
• Cytotoxicity assessment via MTT assay on Caco-2 cells.

Main Results:

• Successful synthesis of a covalent Silibinin-PCL conjugate (Sil-PCLHyd).
• Achieved a Silibinin loading of approximately 9.8 wt.% in the conjugate.
• Sil-PCLHyd demonstrated significantly enhanced cytotoxicity against Caco-2 cells compared to free Silibinin.

Conclusions:

• The proposed two-step hydrolysis and esterification method provides a reliable pathway for creating high drug-loading biopolyester-drug covalent conjugates.
• The developed Silibinin-PCL conjugate exhibits potent cytotoxic effects, suggesting potential for advanced cancer therapy.
• This approach overcomes limitations of physical drug encapsulation in PCL, paving the way for novel drug delivery systems.