Porous biodegradable matrices have various applications in the biomedical sector such as drug carriers. Thermally-induced phase separation (TIPS) is a simple and cost-effective technique for preparation of 3D interconnected microporous matrices. TIPS experimentally allows a one-step matrix fabrication and component incorporation (e.g., nano/microparticles of various fillers or bioactive agents) and also a proper control over matrix porosity, structure and properties. Herein, TIPS process followed by freeze-drying have been used to prepare biodegradable and biocompatible poly(hydroxybutyrate-<i>co</i>-hydroxyvalerate) (PHBV) and poly(butylene succinate) (PBS) matrices with 3D microporous interconnected architecture. Multidirectional and uniaxial cooling systems with different temperature gradients were separately applied to the polymer solutions, resulting in isotropic (randomly-oriented) and anisotropic (uniaxially-oriented, i.e., microtubular) pore distribution, respectively. Polymer matrices with various pore size (from several to tens of microns) and variety of morphologies (from platelet-like, beady and leafy to spherulitic structures) were formed depending on phase separation mechanism. To evaluate the efficacy of the one-step TIPS protocol for manufacturing drug-loaded devices, curcumin (CUR) and piperine (PIP) natural drugs with antibacterial and anti-inflammatory effects were incorporated into the matrices during the fabrication process. The drugs were successfully integrated to the polymer matrix, which was confirmed by physicochemical evaluations. The TIPS-derived drug-loaded devices with uniaxially-oriented porosities could effectively control the release rate. The achieved sustained release was attributed to the restricted drug diffusion through the dense spherulitic pore walls of the microtubular matrices. The TIPS-obtained systems were further validated with marine-derived antibacterial peptides and lipids. The drug-loaded matrices exhibited a sustained release of biobased antibacterial agents over the study period. Our results reveal that porous matrices fabricated by thermally-induced phase separation technique are promising drug delivery devices for sustained release of biobased antimicrobials.

Porous biodegradable matrices fabricated by thermally-induced phase separation (TIPS) for sustained release of antibacterial agents

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