CONTEXT: Surface-modified pH-sensitive liposomal system may be useful for intracellular delivery of chemotherapeutics. OBJECTIVE: Achieving site-specific targeting with over-expressed hyaluronic acid (HA) receptors along with using pH sensitive liposome carrier for intracellular drug delivery was the aim of this study. MATERIALS AND METHODS: Stealth HA-targeted pH-sensitive liposomes (SL-pH-HA) were developed and evaluated to achieve effective intracellular delivery of @entity632 ( @entity3105 ) vis-a-vis enhanced antitumor activity. RESULTS: The in vitro release studies demonstrated that the release of @entity3105 from SL-pH-HA was pH-dependent, i.e. faster at mildly acidic pH    5, compared to physiological pH    7.4. SLpH-HA was evaluated for their @entity137 potential on @entity1759 receptor expressing MCF-7 cells. The half maximal inhibitory concentration (IC50) of SL-pH-HA and SL-HA were about 1.9 and 2.5    M, respectively, after 48   h of incubation. The quantitative uptake study revealed higher localization of targeted liposomes in the receptor positive cells, which was further confirmed by fluorescent microscopy. The antitumor efficacy of the @entity3105 -loaded HA-targeted pH-sensitive liposomes was also verified in a @entity5 xenograft @entity19 model. DISCUSSION: @entity3105 was efficiently delivered to the @entity5 site by active targeting via HA and @entity1759 receptor interaction. The major side-effect of conventional @entity3105 formulation, i.e. @entity1370 was also estimated by measuring serum enzyme levels of LDH and @entity9153 and found to be minimized with developed formulation. Overall, HA targeted pH-sensitive liposomes were significantly more potent than the non-targeted liposomes in cells expressing high levels of @entity1759 . CONCLUSION: Results strongly implies the promise of such liposomal system as an intracellular drug delivery carrier developed for potential anticancer treatment.

Hyaluronic acid modified pH-sensitive liposomes for targeted intracellular delivery of XXXX .

@entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity1759 :: ('960', 'Gene') :: ['CD44'] @entity3105 :: ('D004317', 'Chemical') :: ['DOX'] @entity9153 :: ('5286', 'Gene') :: ['CPK'] @entity1370 :: ('MESH:D066126', 'Disease') :: ['cardiotoxicity']
@entity632 :: (MESH:D004317,Chemical) :: ['doxorubicin']
