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Bethune, Claudette; Blum, Amy Szuchmacher; Geyer, J. Russell; Silber, John R.; Ho, Rodney J. Y.

doi:10.1023/a:1018886321917

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…With a stable and robust enclosed membrane (outer layer), liposome can carry water soluble hydrophilic small molecule drugs as well as protein, RNA, and DNA drugs within the aqueous compartment 7 ; whereas lipophilic drugs such as indinavir and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) were demonstrated to embed stably in the lipid bilayers of lipid nanoparticles. 8, 9 In addition, the liposome membrane is able to protect many drugs from degradative enzymes located at the epithelium and within the circulation, which can improve their absorption and half-life.…”

Section: Introductionmentioning

confidence: 99%

“…8, 9 In this study we have incorporated an integrin targeting peptide into the bilayer and tested the effects of aerosolization on retention of liposome encapsulated aqueous marker, calcein, and target binding activity of RGD expressed on liposomes. When a more hydrophobic compound fentanyl was incorporated into the RGD liposomes, effective analgesic duration was increased and the total AUC effect was enhanced with reduction in plasma drug exposure.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aerosol-Stable Peptide-Coated Liposome Nanoparticles: A Proof-of-Concept Study with Opioid Fentanyl in Enhancing Analgesic Effects and Reducing Plasma Drug Exposure

Hoekman

Srivastava

2014

Journal of Pharmaceutical Sciences

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Previous we reported a novel pressurized olfactory drug (POD) delivery device that deposit aerosolized drug preferentially to upper nasal cavity. This POD device provided sustained CNS levels of soluble morphine analgesic effects. However, analgesic onset of less soluble fentanyl was more rapid but brief, likely due to hydrophobic fentanyl redistribution readily back to blood. To determine whether fentanyl incorporated into an aerosol stable liposome that binds to nasal epithelial cells will enhance CNS drug exposure and analgesic effects and reduce plasma exposure, we constructed RGD liposomes anchored with acylated integrin binding peptides (palmitoyl-GRGDS). The RGD liposomes, which assume gel-phase membrane structure at 25°C were stable under the stress of aerosolization as only 2.2 ± 0.5 % calcein leakage detected. The RGD mediated integrin binding of liposome is also verified to be unaffected by aerosolization. Rats treated with fentanyl in RGD-liposome and POD device exhibited greater analgesic effect, compared to the free drug counterpart (AUCeffect = 1387.l vs. 760.1 %MPE*min); while ~20% reduced plasma drug exposure was noted (AUC0-120 = 208.2 vs 284.8 ng*min/ml). Collectively, fentanyl incorporated in RGD-liposomes are physically and biologically stable under aerosolization, enhanced the overall analgesic effects and reduced plasma drug exposure for the first 2 hours.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%