Effective Delivery of PEGylated siRNA-Containing Lipoplexes to Extraperitoneal Tumours following Intraperitoneal Administration
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Intraperitoneal (i.p.) administration of small interfering RNA (siRNA) has, to date, shown promise in treating tumours located within the peritoneal cavity. The ability of these siRNA molecules to reach extraperitoneal tumours following i.p. administration is, however, yet to be investigated. Here, we examined the impact of PEGylation on the biodistribution of i.p. administered nucleic acids-containing lipoplexes. We showed that in contrast to non-PEGylated liposomes, PEGylated liposomes can deliver siRNA efficiently to extraperitoneal tumours following i.p. administration, resulting in a 45% reduction in tumour size when the oncogene-targeted siRNA was used. This difference was likely contributed by the decreased uptake of PEGylated lipoplexes in the first-pass organs, and, in particular, we observed a 10-fold decrease in the macrophage uptake of these particles compared to non-PEGylated counterparts. Overall, our results indicated the potential of using PEGylated liposomes to deliver siRNA for the treatment of i.p. localized cancer with coexisting extraperitoneal metastasis.
Journal of Drug Delivery
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Oncology and Carcinogenesis not elsewhere classified