4.8 Article

Tuning multilayered polymeric self-standing films for controlled release of L-lactate by electrical stimulation

期刊

JOURNAL OF CONTROLLED RELEASE
卷 330, 期 -, 页码 669-683

出版社

ELSEVIER
DOI: 10.1016/j.jconrel.2020.12.049

关键词

Biphasic voltage pulse; Cardiac tissue regeneration; Cardiomyocytes proliferation; Conducting polymer; Nanoperforated films; Sustained delivery

资金

  1. MINECO-FEDER [RTI2018-098951-B-I00, BES-2015-071997, MAT2015-62725-ERC, RTI2018-096320-B-C21]
  2. Agencia de Gestio d'Ajuts Universitaris i de Recerca [2017SGR359]
  3. Severo Ochoa Programme for Centres of Excellence and RD 2016-2019

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Different approaches were examined for controlled release of L-lactate, with the method of loading L-lactate at the outer PLA layers showing significant influence on the release regulation process. This method can achieve prolonged and sustained release of L-lactate. The biocompatibility and suitability of the engineered films for cardiac tissue engineering has been confirmed.
We examine different approaches for the controlled release of L-lactate, which is a signaling molecule that participates in tissue remodeling and regeneration, such as cardiac and muscle tissue. Robust, flexible, and self-supported 3-layers films made of two spin-coated poly(lactic acid) (PLA) layers separated by an electro-polymerized poly(3,4-ethylenedioxythiophene) (PEDOT) layer, are used as loading and delivery systems. Films with outer layers prepared using homochiral PLA and with nanoperforations of diameter 146 +/- 70 experience more bulk erosion, which also contributes to the release of L-lactic acid, than those obtained using heterochiral PLA and with nanoperforations of diameter 66 +/- 24. Moreover, the release of L-lactic acid as degradation product is accelerated by applying biphasic electrical pulses. The four approaches used for loading extra L-lactate in the 3-layered films were: incorporation of L-lactate at the intermediate PEDOT layer as primary dopant agent using (1) organic or (2) basic water solutions as reaction media; (3) substitution at the PEDOT layer of the ClO4- dopant by L-lactate using de-doping and re-doping processes; and (4) loading of L-lactate at the outer PLA layers during the spin-coating process. Electrical stimuli were applied considering biphasic voltage pulses and constant voltages (both negative and positive). Results indicate that the approach used to load the L-lactate has a very significant influence in the release regulation process, affecting the concentration of released L-lactate up to two orders of magnitude. Among the tested approaches, the one based on the utilization of the outer layers for loading, approach (4), can be proposed for situations requiring prolonged and sustained L-lactate release over time. The biocompatibility and suitability of the engineered films for cardiac tissue engineering has also been confirmed using cardiac cells.

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