Biologically adhesive delivery systems offer important advantages over conventional drug delivery systems. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.
A novel biodegradable poly(lactic acid) microsphere formulation was evaluated for in vivo cytokine immunotherapy of cancer in a human tumor xenograft/ severe combined immunodeficiency (SCID) mouse model. Co-injection of interleukin-2 (IL-2)-loaded microspheres with tumor cells into a subcutaneous site resulted in the complete suppression of tumor engraftment in 80% of animals. In contrast, bovine-serum-albumin(BSA)-loaded particles or bolus injections of poly(ethylene glycol)/IL-2 were ineffective in preventing tumor growth. The antitumor effect of IL-2 released by the microspheres was shown to be mediated by the mouse natural killer cells. This is the first evidence that the rejection of human tumor xenografts can be provoked by the sustained in vivo delivery of IL-2 from biodegradable microspheres. The use of poly(lactic acid) microspheres to deliver cytokines to the tumor environment could provide a safer and simpler alternative to gene therapy protocols in the treatment of cancer.
The sequences of all different RNA transcripts present in a cell or tissue that are related to the gene expression and its functional control represent what it is called a transcriptome. The transcripts vary between cells, tissues, ontogenetic and environmental conditions, and the knowledge that can be gained through them is of a solid relevance for genetic applications in aquaculture. Some of the techniques used in transcriptome studies, such as microarrays, are being replaced for next-generation sequencing approaches. RNA-seq emerges as a new possibility for the transcriptome complexity analysis as well as for the candidate genes and polymorphisms identification of penaeid species. Thus, it may also help to understand the determination of complex traits mechanisms and genetic improvement of stocks. In this review, it is first introduced an overview of transcriptome analysis by RNA-seq, followed by a discussion of how this approach may be applied in genetic progress within penaeid stocks.
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