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A new type of medicated polymeric composite consisting of acyclovir (ACY), polyvinylpyrrolidone K60 (PVP) and polyethylene glycol 6000 (PEG) with core-shell structure were prepared by a coaxial electrospinning process. The composites could enhance the dissolution of the poorly water-soluble drug. The shell layers were formed from a spinnable working fluid containing the filament-forming PVP and citric acid while the core parts were prepared from an un-spinnable co-dissolving solution composed of ACY, sodium hydrate and PEG. Scanning electron microscope and transmission electron microscope observations demonstrated that the composites had a homogeneous linear topography with a slippery surface, a diameter of 670±130 nm, and an obvious core-shell structure. X-ray diffraction (XRD) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy results demonstrated that the drug and citric acid contained in the core and shell parts were in an amorphous status. In vitro dissolution experiments exhibited that ACY was able to be free within 1 min, and the dissolution media were neutral due to acid-basic action within the core-shell structures. The medicated nanocomposites resulted from a combined usage of hydrophilic polymeric excipients PVP and PEG could provide a new solution to the problem associated with the dissolution of poorly water-soluble drugs.

Inbred Lewis and Fisher 344 rat strains differ greatly in drug self-administration; Lewis rats operantly self-administer drugs of abuse including nicotine, whereas Fisher self-administer poorly. As shown herein, operant food self-administration is similar. Based on their pivotal role in drug reward, we hypothesized that differences in basal gene expression in GABAergic neurons projecting from nucleus accumbens (NAcc) to ventral pallidum (VP) play a role in vulnerability to drug taking behavior. The transcriptomes of NAcc shell-VP GABAergic neurons from these two strains were analyzed in adolescents, using a multidisciplinary approach that combined stereotaxic ionotophoretic brain microinjections, laser-capture microdissection (LCM) and microarray measurement of transcripts. LCM enriched the gene transcripts detected in GABA neurons compared to the residual NAcc tissue: a ratio of neuron/residual > 1 and false discovery rate (FDR) <5% yielded 6,623 transcripts, whereas a ratio of >3 yielded 3,514. Strain-dependent differences in gene expression within GABA neurons were identified; 322 vs. 60 transcripts showed 1.5-fold vs. 2-fold differences in expression (FDR<5%). Classification by gene ontology showed these 322 transcripts were widely distributed, without categorical enrichment. This is most consistent with a global change in GABA neuron function. Literature-mining by Chilibot found 38 genes related to synaptic plasticity, signaling and gene transcription, all of which determine drug-abuse; 33 genes have no known association with addiction or nicotine. In Lewis rats, upregulation of Mint-1, Cask, CamkIIδ, Ncam1, Vsnl1, Hpcal1 and Car8 indicates these transcripts likely contribute to altered signaling and synaptic function in NAcc GABA projection neurons to VP.

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