https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45259 sn-glycero-2-phosphocholine and cholesterol were prepared according to the method of dried lipid film hydration. Ligands were conjugated with the surface of liposomes using optimized methods to maximize conjugation efficiency. The liposomes were characterized for particle size, ligand conjugation, drug encapsulation, liposome stability, specificity of binding, cellular internalization, mechanistic pathway of cellular uptake, and cellular toxicity. Results: Both OTR-Lipo and ATO-Lipo showed significant and specific binding to OTRs in a concentration-dependent manner compared to all control groups. There was no significant difference in binding values between OTR-Lipo and ATO-Lipo across all concentrations evaluated. In addition, OTR-Lipo (81.61%±7.84%) and ATO-Lipo (85.59%±8.28%) demonstrated significantly increased cellular internalization in comparison with rabbit IgG immunoliposomes (9.14%±1.71%) and conventional liposomes (4.09%±0.78%) at 2.02 mM phospholipid concentration. Cellular association following liposome incubation at 4.05 mM resulted in similar findings. Evaluation of the mechanistic pathway of cellular uptake indicated that they undergo internalization through both clathrin- and caveolin-mediated mechanisms. Furthermore, cellular toxicity studies have shown no significant effect of both liposomal platforms on cell viability. Conclusion: This study further supports OTRs as a novel pharmaceutical target for drug delivery. OTR-targeted liposomal platforms may provide an effective way to deliver existing therapies directly to myometrial tissue and avoid adverse effects by circumventing non-target tissues.]]> Wed 26 Oct 2022 19:46:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20959 Wed 11 Apr 2018 15:46:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28741 Wed 11 Apr 2018 13:37:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26003 Wed 11 Apr 2018 13:27:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14569 Wed 11 Apr 2018 10:44:13 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43998 Wed 05 Oct 2022 15:10:41 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33962 Wed 04 Sep 2019 10:05:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30033 1 (2,2′-bis[(4-chlorophenyl)methylene]carbonimidic dihydrazide), was active against MRSA and VRE with MIC’s of 8.1 and 4.7 μM, respectively. SAR revealed tolerance for 4-Cl isosteres with 4-F (8), 3-F (9), 3-CH₃ (22), and 4-C(CH₃)₃ (27) (23.7–71 μM) and with 3-Cl (3), 4-CH₃ (21), and 4-CH(CH₃)₂ (26) (8.1–13.0 μM). Imine carbon alkylation identified a methyl/ethyl binding pocket that also accommodated a CH₂OH moiety (75; 2,2′-bis[1-(4-chlorophenyl)-2-hydroxyethylidene]carbonimidic dihydrazide). Analogues 1, 27 (2,2′-bis{[4-(1,1-dimethylethyl)phenyl]methylene}carbonimidic dihydrazide), and 69 (2,2′-bis[1-(4-chlorophenyl)ethylidene]carbonimidic dihydrazide hydrochloride) were active against 24 clinical MRSA and MSSA isolates. No dose-limiting cytotoxicity at ≥2× MIC or hemolysis at ≥8× MIC was observed. Polymyxin B addition engendered Escherichia coli and Pseudomonas aeruginosa Gram-negative activity MIC’s of 4.2–21.6 μM. 1 and 75 displayed excellent microsomal stability, intrinsic clearance, and hepatic extraction ratios with T_1/2 > 247 min, CL_int < 7 μL/min/mg protein, and E_H < 0.22 in both human and mouse liposomes for 1 and in human liposomes for 75.]]> Wed 02 Mar 2022 14:27:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22593 Tue 26 Feb 2019 13:23:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33591 Thu 22 Nov 2018 13:41:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28742 Sat 24 Mar 2018 07:37:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47510 Mon 23 Jan 2023 12:08:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47748 in vivo in a murine model of preterm labour. The aim of this study was to report the pharmaceutical synthesis and characterization of the OTR-PEG-ILs and investigate their specific cellular interaction with OTR-expressing myometrial cells in vitro. Immunoliposomes composed of 1,2-distearoyl-sn-glycero-2-phosphocholine (DSPC) and cholesterol were prepared using an optimized method for the coupling of low concentrations of antibody to liposomes. The liposomes were characterized for particle size, antibody conjugation, drug encapsulation, liposome stability, specificity of binding, cellular internalization, mechanistic pathway of cellular uptake, and cellular toxicity. Cellular association studies demonstrated specific binding of OTR-PEG-ILs to OTRs and significant cellular uptake following binding. Evaluation of the mechanistic pathway of cellular uptake indicated that they undergo internalization through both clathrin- and caveolin-mediated mechanisms. Furthermore, cellular toxicity studies have shown no significant effect of OTR-PEG-ILs or the endocytotic inhibitors on cell viability. This study further supports oxytocin receptors as a novel pharmaceutical target for drug delivery to the uterus.]]> Fri 27 Jan 2023 09:49:49 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42611 Fri 26 Aug 2022 14:51:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46350 Fri 18 Nov 2022 10:03:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32098 Fri 03 Dec 2021 10:35:09 AEDT ]]>