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T*
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T*
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7.3823 0 0 6.5614 210.7842 148.7055 Tm
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[(\(30)7.4(32)7.4(\))]TJ
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0 Tc
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(31)Tj
/F9 1 Tf
8.9663 0 0 8.9663 62.022 94.9039 Tm
0 Tc
(NanoPac)Tj
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6.7246 0 0 5.9768 98.7023 98.9291 Tm
()Tj
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9.843 0 0 9.843 72 78.463 Tm
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[(Na)-3.8(noPa)-3.8(c)]TJ
/F2 1 Tf
7.3823 0 0 6.5614 105.9023 82.885 Tm
0 Tc
()Tj
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T*
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7.3823 0 0 6.5614 183.5149 60.9449 Tm
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[(35,3)-8.8(6)]TJ
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11.1911 67.9242 TD
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[(reconst)5.5(itu)5.6(tio)5.6(n)-512.8(i)5.5(n)-512.8(p)-.2(h)5.6(y)-.2(si)5.5(olo)5.6(g)-.2(ical)-507.1(sal)5.5(i)-.3(ne)-508.2(co)5.6(ntaini)5.5(ng)-512.8(0)5.6(.)3.3(1%)-508.1(pol)5.5(y-)]TJ
0 -1.1174 TD
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0 -1.1116 TD
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[(by)-317.5(sy)5(stemic)-318.7(circulatio)5(n,)-314.1(but)-317.7(with)]TJ
13.0285 0 TD
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-13.0285 -1.1116 TD
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[(d)-5.5(r)-5.4(u)-5.5(g)-339.5(r)-5.4(e)-.9(l)-5.6(e)-.9(a)-6.6(s)-5.3(e)-340.7(c)-6.6(ha)-6.6(r)-5.4(a)-.9(c)-6.6(t)-5.6(er)-5.4(i)-5.6(s).5(t)-5.6(i)-5.6(c)-.9(s)-345.1(o).3(f)-345.2(s).5(m)-6.7(a)-6.6(ll)-5.6(er)-345.2(pa)-6.6(r)-5.4(t)-5.6(ic)-6.6(le)-6.6(s)-5.3(,)-341.9(lo)-5.5(c)-6.6(a)-.9(l)-345.4(a)-.9(d)-5.5(m)-.9(i)-5.6(n)-5.4(is)-5.3(-)]TJ
T*
[(t)-5.6(r)-5.4(at)-5.6(i)-5.6(o).3(n)-310.7(o)-5.5(f)-310.7(N)-6.3(an)-5.5(oP)-5.3(a)-6.6(c)-311.9(di)-5.6(r)-5.4(e)-.9(c)-6.6(t)-5.6(ly)-310.7(a)-6.6(t)-310.9(ma)-6.6(li)-5.6(g)-5.5(n).3(a)-6.6(n)-5.5(t)-305.1(s)-5.3(i)-5.6(t)-5.6(e)-.9(s)-310.5(p)-5.5(r)-5.4(o).3(v)-5.5(i)-5.6(de)-6.6(s)-310.5(a)-311.9(de)-6.6(po)-5.5(t)]TJ
0 -1.1174 TD
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0 -1.1116 TD
[(con)5.4(s)-.2(tant)-334.6(s)5.6(a)-1.5(tu)5.4(rat)5.3(i)-.5(on)-328.7(level)5.3(s)-.2(.)]TJ
7.3823 0 0 6.5614 411.1369 663.7605 Tm
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(36)Tj
9.843 0 0 9.843 323.0361 648.4534 Tm
0 Tc
(Although)Tj
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4.2622 0 TD
[(in)-474.6(vitro)]TJ
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3.6286 0 TD
[(dissolution)-478.8(methods)-482.3(have)-479(been)-479(mar-)]TJ
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[(ginally)-377.9(useful)-370.5(for)-377.6(evaluating)-372(the)-373.2(release)-380.9(of)-370.8(paclitaxel)-379.1(from)]TJ
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[(NanoPac,)-476.1(unpublished)]TJ
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9.6993 0 TD
[(in)-468.9(vivo)]TJ
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3.3925 0 TD
[(trials)-468.7(and)-471(a)-468.8(phase)-468.4(1)-467.6(intra-)]TJ
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[(peritoneal)-504.4(clinical)-496.6(study)-500.8(have)-496.3(demonstrated)-501.8(the)-499.9(extended)]TJ
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[(release)-380.9(prole.)-374(Twenty-one)-378.4(patients)-374.2(with)-374.2(peritoneal)-377.7(malig-)]TJ
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[(nanci)-8(es)-446.7(received)-445.5(intraperitoneal)-453.7(\(IP\))-447.6(doses)-449.8(of)-445.7(50275)-167.9(mg/)]TJ
T*
(m)Tj
7.3823 0 0 6.5614 320.7684 587.0549 Tm
(2)Tj
9.843 0 0 9.843 324.4535 582.6896 Tm
[(,)-326(i)0(n)-319.1(u)0(p)-324.7(t)0(o)-324.9(six)-320(cycles)-326.8(\(every)-325.6(28)-324.7(days\);)-324.5(the)-321.4(peritoneal)-331.7(uid)]TJ
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[(paclitaxel)-321.5(concentrations)-314(were)-318.6(4502900)-314.1(times)-313.2(greater)-316.5(than)]TJ
0 -1.1174 TD
[(systemic)-392.4(plasma,)-382.2(resulting)-391.4(in)-382.5(fewer)-383(toxic-relat)-10.3(ed)-383.5(events)-383.3(in)]TJ
0 -1.1116 TD
[(comparison)-337(with)-339.6(intravenous)-337(trials.)]TJ
7.3823 0 0 6.5614 454.7904 554.1731 Tm
(36)Tj
9.843 0 0 9.843 323.0361 538.866 Tm
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[(Wit)-15.7(h)-236.9(its)-247(s)-15.7(l)11(o).5(w)-248(d).5(e)-15.7(p)9.7(ot)-247.3(re)-15.7(l)9.6(eas)-15.7(e)-237.7(prop)-15.7(e)9.7(r).5(tie)-15.7(s)9.9(,)-249.5(aeros)-15.7(o)11.1(l).4(i)-15.7(z)9.6(ed)-247.2(Nan)-15.7(o)10.9(Pac)]TJ
-1.0137 -1.1174 TD
0 Tc
[(may)-483.7(have)-479(the)-476.9(potential)-479.3(to)-480.4(provide)-481.3(a)-474.6(meaningful)-481.3(survival)]TJ
0 -1.1116 TD
[(benet)-256.6(for)-250.9(patients)-253.2(with)-247.4(lung)-252.2(cancer.)-250.8(Following)-252.9(nebulization)]TJ
T*
[(and)-401.9(deposition)-404(within)-405.3(the)-402(alveolar)-404.2(sacs,)-401.4(rapid)-404.2(diffusion)-401.6(of)]TJ
0 -1.1174 TD
[(the)-396.3(saline)-400.7(would)-392.4(theoretically)-399.7(leave)-400.8(NanoPac)-397.8(particles)-393.7(be-)]TJ
0 -1.1116 TD
[(hind)-355.9(for)-354.6(constant)-351(release)-357.8(of)-353.5(bioavailable)-358.2(paclitaxel)-356(directly)]TJ
T*
[(to)-399.7(pulmonary)-404.1(surfactant)-406.2(and)-401.9(malignant)-399.8(cells.)-403(In)-399.6(this)-401.9(study)]TJ
0 -1.1174 TD
[(we)-465(explore)-459.4(the)-465.4(feasibility)-458.4(and)-465.2(pharmacokinetics)-462.6(of)-462.9(nebu-)]TJ
0 -1.1116 TD
[(lized)-336.4(NanoPac)-340.2(for)-331.5(inhalation)-336.4(therapy)-338.4(in)-330.6(a)-336.3(rodent)-336.2(model.)]TJ
/F4 1 Tf
8.9663 0 0 8.9663 313.0582 427.4078 Tm
[(Materials)-339(and)-331.9(Methods)]TJ
/F6 1 Tf
9.843 0 0 9.843 323.0361 410.9668 Tm
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[(Al)-15.8(l)-565.4(a)-.8(nima)-15.8(l)-566.5(proc)-15.8(e)8.5(dur)-15.8(e)9.7(s)-575.4(wer)-15.8(e)-566.3(condu)-15.8(c)9.6(t).3(ed)-575.6(un)-15.8(d)10.8(e)-.8(r)-575.5(p).4(r)-15.8(o)10.8(toc)-15.8(o)9.6(ls)]TJ
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[(a)-15.9(p)9.5(pro)-15.9(v)10.7(e)-.9(d)-333.8(b).3(y)-333.8(t)-15.9(h)10.6(e)-334.9(Ins)-15.9(t)10.8(itu)-15.9(t)10.6(i).2(ona)-15.9(l)-324.7(A)-.6(nima)-15.9(l)-324.7(C)-.7(are)-334.9(a)-.9(n)-15.9(d)-323.4(Use)-334.9(C)-.7(o)-15.9(m)9.5(mit-)]TJ
0 -1.1174 TD
0 Tc
[(te)25.3(e)-480.3(\()0(I)26.7(A)15.3(C)15.2(U)15.3(C\))-469.7(a)15(t)-485(L)15(o)16.2(v)16.2(e)15(la)25.3(c)15(e)-480.3(B)15.2(i)0(o)26.5(m)15(e)15(d)16.2(ic)25.3(a)15(l)-479.3(\(A)25.8(l)16(b)16.2(u)16.2(q)0(u)26.6(e)15(r)16.2(q)0(u)26.6(e)15(,)-481.5(N)15.3(M)15.3(\))0(,)]TJ
0 -1.1116 TD
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[(w)-15.8(h)9.9(ich)-391.3(i).3(s)-385.3(a)-15.8(c)8.5(c)-.8(red)-15.8(i)10.7(ted)-391.3(b).4(y)-385.5(t)-15.8(h)10.7(e)-386.7(As)-15.8(s)11.2(o).4(ci)-15.8(a)9.5(tio)-15.8(n)-375.1(for)-391.2(Ass)-15.8(e)9.8(ss)-15.8(m)9.8(e)-.8(nts)-391.1(a)-.8(nd)]TJ
T*
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