1. Investigation of cationized triblock and diblock poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers for oral delivery of enoxaparin: In vitro approach
- Author
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Anne Sapin-Minet, Philippe Maincent, Pimchanok Charoongchit, Jiraphong Suksiriworapong, Shirui Mao, Varaporn Buraphacheep Junyaprasert, Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Shenyang Pharmaceutical University, Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), and Université de Lorraine (UL)
- Subjects
Poly(ε-carprolactone)-co-poly(ethylene glycol) copolymers ,MESH: Cell Death ,Cell Membrane Permeability ,[SDV]Life Sciences [q-bio] ,Administration, Oral ,Nanoparticle ,Polymer architecture ,02 engineering and technology ,01 natural sciences ,Biochemistry ,Polyethylene Glycols ,Cationic copolymer ,chemistry.chemical_compound ,Drug Delivery Systems ,Copolymer ,MESH: Cell Membrane Permeability ,[PHYS]Physics [physics] ,Cell Death ,Temperature ,Biomaterial ,General Medicine ,021001 nanoscience & nanotechnology ,MESH: Polyesters ,MESH: Temperature ,Oral delivery ,MESH: Administration, Oral ,MESH: Caco-2 Cells ,0210 nano-technology ,Caprolactone ,Biotechnology ,MESH: Enoxaparin ,Materials science ,Surface Properties ,Polyesters ,MESH: Drug Delivery Systems ,Biomedical Engineering ,MESH: Imaging, Three-Dimensional ,010402 general chemistry ,Biomaterials ,Imaging, Three-Dimensional ,Cations ,PEG ratio ,Polymer chemistry ,Humans ,MESH: Drug Liberation ,[CHIM]Chemical Sciences ,MESH: Particle Size ,Particle Size ,Enoxaparin ,MESH: Cations ,Molecular Biology ,MESH: Surface Properties ,MESH: Humans ,Cationic polymerization ,0104 chemical sciences ,Drug Liberation ,MESH: Polyethylene Glycols ,chemistry ,Nanoparticles ,Caco-2 Cells ,Ethylene glycol ,Nuclear chemistry - Abstract
In this study, poly( e -caprolactone)-co-poly(ethylene glycol) copolymers grafted with a cationic ligand, propargyltrimethyl ammonium iodide (PTA), to fabricate the cationized triblock (P(CatCLCL) 2 -PEG) and diblock (P(CatCLCL)-mPEG) copolymers were investigated their potential use for oral delivery of enoxaparin (ENX). Influences of various PTA contents and different structures of the copolymers on molecular characteristics, ENX encapsulation, particle characteristics, and capability of drug transport across Caco-2 cells were elucidated. The results showed that P(CatCLCL) 2 -PEG and P(CatCLCL)-mPEG copolymers self-aggregated and encapsulated ENX into spherical particles of ∼200–450 nm. The increasing amount of PTA on the copolymers increased encapsulation efficiency of over 90%. The ENX release from both types of the cationized copolymer particles was pH-dependent which was retarded at pH 1.2 and accelerated at pH 7.4, supporting the drug protection in the acidic environment and possible release in the blood circulation. The toxicity of ENX-loaded particles on Caco-2 cells decreased when decreasing the amount of PTA. The triblock and diblock particles dramatically enhanced ENX uptake and transport across Caco-2 cells as compared to the ENX solution. However, the different structures of the copolymers slightly affected ENX transport. These results suggested that P(CatCLCL) 2 -PEG and P(CatCLCL)-mPEG copolymers would be potential carriers for oral delivery of ENX. Statement of Significance The anionic drugs such as proteins, peptides or polysaccharides are generally administered via invasive route causing patient incompliance and high cost of hospitalization. The development of biomaterials for non-invasive delivery of those drugs has gained much attention, especially for oral delivery. However, they have limitation due to non-biocompatibility and poor drug bioavailability. In this study, the novel poly( e -caprolactone)-co-poly(ethylene glycol) copolymers grafted with propargyltrimethyl ammonium iodide, a small cationic ligand, were introduced to use as a carrier for oral delivery of enoxaparin, a highly negatively charged drug. The study showed that these cationized copolymers could achieve high enoxaparin entrapment efficiency, protect drug release in an acidic environment and enhance enoxaparin permeability across Caco-2 cells, the intestinal cell model. These characteristics of the cationized copolymers make them a potential candidate for oral delivery of anionic drugs for biomaterial applications.
- Published
- 2017