Ultrasound-Mediated Release of Hydrophilic and Lipophilic Agents From Echogenic Liposomes

Abstract

AbbreviationsC-ELIP, calcein-loaded echogenic liposome; ELIP, echogenic liposome; MDI, mean digital intensity; MI, mechanical index; P-ELIP, papaverine-loaded echogenic liposome; ROI, region of interest; rt-PA, recombinant tissue plasminogen activator he clinical need for organ-or tissue-specific drug delivery, also known as targeted drug delivery, arises when systemic delivery of a drug in sufficient doses to achieve a therapeutic effect at the target site results in deleterious systemic effects. Relevant clinical problems include delivery of chemotherapeutic drugs to tumors, delivery of thrombolytic drugs to the cerebral or coronary circulation during ischemic stroke T ArticleObjective. To achieve ultrasound-controlled drug delivery using echogenic liposomes (ELIPs), we assessed ultrasound-triggered release of hydrophilic and lipophilic agents in vitro using color Doppler ultrasound delivered with a clinical 6-MHz compact linear array transducer. Methods. Calcein, a hydrophilic agent, and papaverine, a lipophilic agent, were each separately loaded into ELIPs. Calceinloaded ELIP (C-ELIP) and papaverine-loaded ELIP (P-ELIP) solutions were circulated in a flow model and treated with 6-MHz color Doppler ultrasound or Triton X-100. Treatment with Triton X-100 was used to release the encapsulated calcein or papaverine content completely. The free calcein concentration in the solution was measured directly by spectrofluorimetry. The free papaverine in the solution was separated from liposome-bound papaverine by spin column filtration, and the resulting papaverine concentration was measured directly by absorbance spectrophotometry. Dynamic changes in echogenicity were assessed with low-output B-mode ultrasound (mechanical index, 0.04) as mean digital intensity. Results. Color Doppler ultrasound caused calcein release from C-ELIPs compared with flow alone (P < .05) but did not induce papaverine release from P-ELIPs compared with flow alone (P > .05). Triton X-100 completely released liposome-associated calcein and papaverine. Initial echogenicity was higher for C-ELIPs than P-ELIPs. Color Doppler ultrasound and Triton X-100 treatments reduced echogenicity for both CELIPs and P-ELIPs (P < .05). Conclusions. The differential efficiency of ultrasoundmediated pharmaceutical release from ELIPs for water-and lipid-soluble compounds suggests that water-soluble drugs are better candidates for the design and development of ELIP-based ultrasound-controlled drug delivery systems.

An in vitro feasibility study of controlled drug release from encapsulated nanometer liposomes using high intensity focused ultrasound

“…Our previous study demonstrated that when exposed to 2.2 MHz 10% duty cycle pulsed US (in situ spatial pulse peak intensity, I SPPA = 80 W/cm 2 ), liposomes served as cavitation nuclei were able to promote acoustic cavitation during sonoporation process [10]; cavitation in turn enhanced the drug uptake by the cells. A study by Kopechek et al [11] showed that 6-MHz ultrasound (continuous wave, 2-7 W/cm 2 ) could induce leakage from liposomes of mean diameter 780 nm. The percentage of calcein, the fluorescence marker encapsulated in the liposomes, released from liposomes reached 47.5 ± 33%.…”

Passive cavitation imaging with ultrasound arrays

“…[8][9][10] Ultrasound-induced cavitation also offers the exciting possibility of targeted drug and gene delivery using lipid-coated microbubbles which can encapsulate bioactive materials. [11][12][13] Cavitation activity occurring during ultrasound ablation of soft tissue 14,15 is postulated to increase ultrasound absorption. 16 This can result in faster treatments but can also complicate energy deposition and distort ablative lesion shapes.…”

Electrochemically Stimulated Release from Liposomes Embedded in a Polyelectrolyte Multilayer

“…They were able to employ a quick and effi cient procedure of spraying [ 14,15 ] for the fabrication of such composite fi lms. Finally, they demonstrated the release of fl uorescent dyes contained in the embedded vesicles triggered by temperature increase up to 45 ° C. [ 16 ] Triggered release of drugs from liposomes in various systems without polyelectrolytes has been implemented in several different mechanisms, like light, [ 17,18 ] redox reactions, [ 19 ] ultrasound, [20][21][22] magnetic fi elds, [ 23 ] near IR, [ 24 ] and pH, [ 25,26 ] each with its specifi c advantage depending on application. Electrochemically stimulated release is an especially attractive release mechanism for surface based systems since it makes low-cost, spatially controlled release possible by using microelectrodes produced by standard semiconducting technology.…”