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

JOURNAL OF CONTROLLED RELEASE

卷:330

Article

Puiggali-Jou, Anna^1,2  Ordono, Jesus^3,4  del Valle, Luis J.^1,2  Perez-Amodio, Soledad^3,4,5  Engel, Elisabeth^3,4,5  Aleman, Carlos^1,2,3 

[1] Univ Politecn Cataluna, EEBE, Dept Engn Quim, C Eduard Maristany 10-14,Ed I2, Barcelona 08019, Spain

[2] Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Eduard Maristany 10-14,Ed C, Barcelona 08019, Spain

[3] Barcelona Inst Sci & Technol, Inst Bioengn Catalonia IBEC, Baldiri Reixac 10-12, Barcelona 08028, Spain

[4] CIBER BBN, CIBER Bioingn Biomat & Nanomed, Zaragoza 50018, Spain

[5] Univ Politecn Catalunya UPC, Mat Sci & Met Engn, EEBE, C Eduard Maristany 10-14, Barcelona 08019, Spain

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

DOI  :  10.1016/j.jconrel.2020.12.049

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free