Multi-responsive on-demand drug delivery PMMA-co-PDEAEMA platform based on CO2, electric potential, and pH switchable nanofibrous membranes.

This study investigated the release characteristics of curcumin (CUR)-loaded switchable poly(methyl methacrylate)-co-poly(N,N-diethylaminoethyl methacrylate) (PMMA-co-PDEAEMA) membranes following the application of various stimuli, as well as the platform's applicability in wound dressing and tissue engineering applications. The free-radical polymerization method was used to synthesize the PMMA-co-PDEAEMA copolymer. The drug-loaded nanofibrous membrane with electric potential (EP)-, CO2-, and pH-responsive properties was developed by the electrospinning of PMMA-co-PDEAEMA and CUR. The resulted structure was characterized by a scanning electron microscope (SEM) coupled with X-ray energy dispersive spectroscopy and wide-angle X-ray scattering measurements. The release characteristics of the CUR-loaded wound covering were analyzed in various simulated environments at varying voltages, alternated CO2/N2 gas bubbling, and at two different pH values; the results demonstrated high drug release controllability. Loaded CUR displayed high stability and better solubility compared with free CUR. The CUR-loaded tissue also exhibited high antibacterial activity against Escherichia coli and staphylococcus aureus bacteria. In addition, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay depicted high biocompatibility of up to 95% in the CUR-loaded membrane. This platform could be a promising candidate for usage in tissue engineering and medical applications such as targeted drug delivery, biodetection, reversible cell capture-and-release systems, and biosensors.

Cloning, functional characterization and genomic organization of 1,8-cineole synthases from Lavandula.

Several members of the genus Lavandula produce valuable essential oils (EOs) that are primarily constituted of the low molecular weight isoprenoids, particularly monoterpenes. We isolated over 8,000 ESTs from the glandular trichomes of L. x intermedia flowers (where bulk of the EO is synthesized) to facilitate the discovery of genes that control the biosynthesis of EO constituents. The expression profile of these ESTs in L. x intermedia and its parents L. angustifolia and L. latifolia was established using microarrays. The resulting data highlighted a differentially expressed, previously uncharacterized cDNA with strong homology to known 1,8-cineole synthase (CINS) genes. The ORF, excluding the transit peptide, of this cDNA was expressed in E. coli, purified by Ni-NTA agarose affinity chromatography and functionally characterized in vitro. The ca. 63 kDa bacterially produced recombinant protein, designated L. x intermedia CINS (LiCINS), converted geranyl diphosphate (the linear monoterpene precursor) primarily to 1,8-cineole with K ( m ) and k ( cat ) values of 5.75 µM and 8.8 × 10(-3) s(-1), respectively. The genomic DNA of CINS in the studied Lavandula species had identical exon-intron architecture and coding sequences, except for a single polymorphic nucleotide in the L. angustifolia ortholog which did not alter protein function. Additional nucleotide variations restricted to L. angustifolia introns were also observed, suggesting that LiCINS was most likely inherited from L. latifolia. The LiCINS mRNA levels paralleled the 1,8-cineole content in mature flowers of the three lavender species, and in developmental stages of L. x intermedia inflorescence indicating that the production of 1,8 cineole in Lavandula is most likely controlled through transcriptional regulation of LiCINS.