Mucus barriers lining mucosal epithelia reduce the effectiveness of nanocarrier-based mucosal drug delivery and imaging (��theranostics��). liposomes. However increasing PEG content to ~12 mol% compromised BA loading and vaginal distribution suggesting that PEG content must be optimized to maintain drug loading and stability. Non-invasive diaCEST MRI illustrated uniform vaginal coverage and longer retention of BA-loaded 7 mol %-PEG liposomes compared to unencapsulated BA. Liposomal MPP with optimized PEG content hold promise for drug delivery and imaging at mucosal surfaces. CEST contrast AZD8931 was generally consistent with the BA loading level. Figure 1 Mobility of PEGylated and non-PEGylated DSPC liposomes 0 h or 3 h post addition to CVM. A. Representative liposome trajectories over 1 s. B. as a function of time scale. C. Distributions of the logarithms of individual liposome MSD. … Table 2 Characterization of BA-loaded liposomes We next investigated the vaginal distribution of BA-loaded liposomes in the vaginas of mice in the estrus phase of their estrous cycle.5 Particle mobility in mucus Rabbit polyclonal to TP73. has been demonstrated to correlate with mucosal distribution.5-7 Similarly we observed non-uniform distribution of mucoadhesive non-PEGylated liposomes which appeared to outline mucin bundles (Figure 2 A). This non-uniform distribution was also reflected by a high AZD8931 variance-to-mean ratio (VMR increased VMR reflects decreased uniformity) (Figure 2 E). While all PEGylated liposomes provided improved vaginal distribution 7 mol%-PEG liposomes demonstrated the most uniform coverage with the lowest VMR. Additionally individual cell outlines were observed implying that the 7 mol%-PEG liposomes were able to reach the vaginal epithelium (Figure 2 C). Liposomes with less PEG content may be insufficiently shielded to avoid mucoadhesion (Figure 2 D) perhaps due to their disassembly via micellization distribution. Moderately PEGylated liposomes (~7 mol%) maintained encapsulation efficiency while distributing most uniformly in the mouse vagina. Using non-invasive diaCEST MRI we showed that liposomal MPP provided uniform vaginal coverage and retained BA for �� 90 min in vivo. These results demonstrate the potential of liposomal MPP for mucosal delivery and imaging and suggest that liposomal MPP formulations may be suitable for theranostics in mucosal surfaces like that of the vagina. Supplementary Material Click here to view.(162K docx) Acknowledgements We thank Ming Yang for helpful discussions and Joshua Kays for technical assistance. Statements AZD8931 of Funding: This work was supported in part by NIH AZD8931 AZD8931 grants R01EB015031 R01EB015032 and S10RR028955. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health. Abbreviations BAbarbituric acidCVMcervicovaginal mucusdiaCESTdiamagnetic chemical exchange saturation transferMPPmucus-penetrating particlesMPTmultiple particle trackingMRImagnetic resonance imagingPEGpolyethylene glycolDSPC1 2 2 poly(ethylene glycol)2000 Footnotes Publisher’s Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting typesetting and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content and all legal disclaimers that apply to the journal pertain. Disclosure of conflicts of interest: The mucus-penetrating particle technology is being developed by Kala Pharmaceuticals. J.H. is co-founder and consultant to Kala and owns company stock which is subject to certain restrictions under Johns Hopkins University policy. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest.