Lipophilic Agents Research Articles

Fabrication of protein-stabilized nanoemulsions using a combined homogenization and amphiphilic solvent dissolution/evaporation approach

Oil-in-water nanoemulsions containing small lipid droplets ( d < 100 nm) are finding increasing applications within the food industry as delivery systems in transparent foods and beverages, and to increase the bioavailability of lipophilic active agents. In this study, we show that nanoemulsions can be fabricated from food-grade ingredients (corn oil, whey protein, and water) using simple processing operations (homogenization, dilution and solvent evaporation). Nanoemulsions were formed by homogenizing 10 wt% organic phase (corn oil and ethyl acetate) with 90 wt% aqueous phase (water and whey protein isolate). The mean particle diameter of the emulsions decreased with increasing ethyl acetate concentration in the organic phase, which was attributed to its ability to alter the size of the droplets produced during homogenization, as well as its ability to be removed from the droplets by dissolution and/or evaporation after homogenization. The particle size also decreased with increasing emulsifier concentration. These nanoemulsions may be useful as delivery systems in the food, pharmaceutical and cosmetics industries.

SLN for topical application in skin diseases—Characterization of drug–carrier and carrier–target interactions

The modes of drug–particle interactions considerably influence drug delivery by nanoparticulate carrier systems and drug penetration into the skin. The exact mechanism of the drug loading and its release are still ambiguous. Therefore, the loading process, the interaction of the agent and the lipid matrix of solid lipid nanoparticles (SLNs) as well as the uptake of the loaded agent by skin lipids were analysed by electron spin resonance (ESR) and parelectric spectroscopy (PS) using spin probes (TEMPO, TEMPOL, and CAT-1) as model drugs differing in their lipophilicity. The spin probes were closely attached to the particles lipid surface (TEMPO) or located in the layers of the surfactant (CAT-1), respectively. Furthermore, two distinct sub-compartments on the SLN were found. To simulate the processes at the phase boundary SLN dispersion/skin, skin lipid mixtures were prepared and the transfer process of the spin labels was followed by ESR tomography. Transfer rates were related to the lipophilicity of the spin probe, the lipid mixture and the applied pharmaceutical formulation, SLN dispersion and aqueous solution, respectively. In particular, SLN accelerated in particular the distribution of the lipophilic agents.

Intraoperative Near‐Infrared Fluorescent Cholangiography (NIRFC) in Mouse Models of Bile Duct Injury

Accidental injury to the common bile duct is a rare but serious complication of laparoscopic cholecystectomy. Accurate visualization of the biliary ducts may prevent injury or allow its early detection. Conventional X-ray cholangiography is often used and can mitigate the severity of injury when correctly interpreted. However, it may be useful to have an imaging method that could provide real-time extrahepatic bile duct visualization without changing the field of view from the laparoscope. The purpose of the present study was to test a new near-infrared (NIR) fluorescent agent that is rapidly excreted via the biliary route in preclinical models to evaluate intraoperative real-time near infrared fluorescent cholangiography (NIRFC). To investigate probe function and excretion, a lipophilic near-infrared fluorescent agent with hepatobiliary excretion was injected intravenously into one group of C57/BL6 control mice and four groups of C57/BL6 mice under the following experimentally induced conditions: (1) chronic biliary obstruction, (2) acute biliary obstruction (3) bile duct perforation, and (4) choledocholithiasis, respectively. The biliary system was imaged intravitally for 1 h with near-infrared fluorescence (NIRF) with an intraoperative small animal imaging system (excitation 649 nm, emission 675 nm). The extrahepatic ducts and extraluminal bile were clearly visible due to the robust fluorescence of the excreted fluorochrome. Twenty-five minutes after intravenous injection, the target-to-background ratio peaked at 6.40 +/- 0.83 but signal was clearly visible for ~60 min. The agent facilitated rapid identification of biliary obstruction and bile duct perforation. Implanted beads simulating choledocholithiasis were promptly identifiable within the common bile duct lumen. Near-infrared fluorescent agents with hepatobiliary excretion may be used intraoperatively to visualize extrahepatic biliary anatomy and physiology. Used in conjunction with laparoscopic imaging technologies, the use of this technique should enhance hepatobiliary surgery.

99mTc-tricarbonyl labeled agents for cell labeling: Development, biodistribution in normal mice and preliminary in vitro evaluation

We have developed four 99mTc(CO) 3-labeled lipophilic tracers as potential radiolabeling agents for cells based on a hexadecyl tail. 99mTc(CO) 3-hexadecylamino- N, N′-diacetic acid (negatively charged), 99mTc(CO) 3-hexadecylamino- N-α-picolyl- N′-acetic acid (uncharged), 99mTc(CO) 3- N, N′-dipicolylhexadecylamine (positively charged), 99mTc(CO) 3- N-hexadecylaminoethyl- N′-aminoethylamine (positively charged) were prepared in a radiolabeling yield: >90%. Preliminary cell uptake studies were performed in mixed blood cells with or without plasma and were compared with 99mTc-d,l-HMPAO and [ 18F]FDG. In plasma-free blood cells, maximum uptake (78%) was obtained for 99mTc(CO) 3- N-hexadecylaminoethyl- N′-aminoethylamine after 60 min incubation (compared to 55% and 23% for 99mTc-d,l-HMPAO and [ 18F]FDG, respectively) while in plasma-rich medium, 99mTc(CO) 3- N, N′-dipicolylhexadecylamine was best bound (54%, similar to the binding of 99mTc-d,l-HMPAO). Biodistribution in normal mice showed mainly hepatobiliary clearance of the agents and initial high lung uptake. The radiolabeled compounds showed good blood clearance with maximally 7.9% injected dose per gram at 60 min post injection. While the least lipophilic agent ( 99mTc(CO) 3- N, N′-dipicolylhexadecylamine, log P = 1.3) showed the best cell uptake, there appears to be no direct correlation between lipophilicity and tracer uptake in mixed blood cells. In view of its comparable cell uptake to well known cell labeling agent 99mTc-d,l-HMPAO, 99mTc(CO) 3- N, N′-dipicolylhexadecylamine merits further evaluation as a potential cell labeling agent.

Adjustment of dosing of antimicrobial agents for bodyweight in adults

Adjustment of dosing of antimicrobial agents for bodyweight in adults

Accumulation of Eu3+ chelates in cells expressing or not P-glycoprotein: Implications for blood–brain barrier crossing

Alzheimer's disease (AD) is the most commonly form of dementia in the elderly. The development of molecules able to detect biomarkers characteristic of AD is critical to its understanding and treatment. However, such molecules must be able to pass blood-brain barrier (BBB) which is a major impediment to the entry of many therapeutic drugs into the brain. Such a limitation applies to the development of magnetic resonance imaging molecular neuroimaging agents using biomarkers of AD-like beta-amyloid deposits, as the common extracellular contrast agents (CAs) are not able to cross an intact BBB. In this work, we have studied the ability of a series of simple Eu(3+) complexes to enter cells overexpressing or not the ABCB1 (P-gp or P-glycoprotein) protein, which is expressed at the BBB and in human embryonic astrocytes. The intracellular uptake of the Eu(3+) complexes of linear and macrocyclic polyaminocarboxylate ligands with different charges and lipophilicities was followed by atomic absorption spectrometry. Based on biochemical argument, we propose that lipophilic contrast agents can be efficiently taken up by cells and accumulate inside mitochondria when they are positively charged. The important point is that they are not P-gp substrates, which is one of the major obstacles for them to cross the BBB.

In Vivo Detection of Embryonic Stem Cell–Derived Cardiovascular Progenitor Cells Using Cy3-Labeled Gadofluorine M in Murine Myocardium

The aim of the current study is to test the ability to label and detect murine embryonic stem cell-derived cardiovascular progenitor cells (ES-CPC) with cardiac magnetic resonance (CMR) using the novel contrast agent Gadofluorine M-Cy3 (GdFM-Cy3). Cell therapy shows great promise for the treatment of cardiovascular disease. An important limitation to previous clinical studies is the inability to accurately identify transplanted cells. GdFM-Cy3 is a lipophilic paramagnetic contrast agent that contains a perfluorinated side chain and an amphiphilic character that allows for micelle formation in an aqueous solution. Previous studies reported that it is easily taken up and stored within the cytosol of mesenchymal stem cells, thereby allowing for paramagnetic cell labeling. Investigators in our laboratory have recently developed techniques for the robust generation of ES-CPC. We reasoned that GdFM-Cy3 would be a promising agent for the in vivo detection of these cells after cardiac cell transplantation. ES-CPC were labeled with GdFM-Cy3 by incubation. In vitro studies were performed to assess the impact of GdFM-Cy3 on cell function and survival. A total of 500,000 GdFM-Cy3-labeled ES-CPC or control ES-CPC were injected into the myocardium of mice with and without myocardial infarction. Mice were imaged (9.4-T) before and over a 2-week time interval after stem cell transplantation. Mice were then euthanized, and their hearts were sectioned for fluorescence microscopy. In vitro studies demonstrated that GdFM-Cy3 was easily transfectable, nontoxic, stayed within cells after labeling, and could be visualized using CMR and fluorescence microscopy. In vivo studies confirmed the efficacy of the agent for the detection of cells transplanted into the hearts of mice after myocardial infarction. A correspondence between CMR and histology was observed. The results of the current study suggest that it is possible to identify and potentially track GdFM-Cy3-labeled ES-CPC in murine infarct models via CMR.

Connexin channels and phospholipids: association and modulation

BackgroundFor membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood.ResultsEndogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred.ConclusionThis study is the first to identify (endogenous) phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents.

Nanoparticle Coated Emulsions as Novel Dermal Delivery Vehicles

The dermal delivery characteristics of hydrophilic silica nanoparticle coated medium chain triglyceride oil-in-water emulsions are reported and correlated with the physicochemical and interfacial properties of the emulsion based drug carriers. The synergistic drug/stabiliser/nanoparticle interactions are demonstrated to be a function of the charge and concentration of the initial emulsion stabiliser; charge and initial loading phase of nanoparticles and physicochemical properties of the drug molecule. The improved physical stability of the emulsions and the chemical stability of two model lipophilic agents (all-trans-retinol and acridine orange 10-nonyl bromide) confirm that engineered nanoparticle layers can enhance the shelf-life of liable lipophilic agents. Nanoparticle coatings are shown to control the in-vitro release of active agents from emulsions and significantly promote skin retention. The lipophilic agents distributed into the deeper viable skin layers without permeation through full-thickness skin and hence systemic exposure. Nanoparticle-coated submicron oil-in-water emulsions can serve as novel dermal carriers with controlled release kinetics and targeted drug delivery.

Biocompatible Microemulsions for Fabrication of Glyceryl Monostearate Solid Lipid Nanoparticles (SLN) of Tretinoin

The objective of the present investigation was to fabricate glyceryl monostearate SLN by employing a biocompatible microemulsion as a template. Biocompatible excipients such as Tween 20 (as a surfactant) and Transcutol P (a cosourfactant) (at different K(m) ratios) were selected for the fabrication of microemulsions. Pseudo-ternary phase diagrams were plotted to identify the area of the microemulsion existence. Glyceryl monostearate SLN were fabricated by dispersing the microemulsion (maintained at 65 degrees C) into cold water (maintained at 2-3 degrees C). The particle size of the SLN was determined by photon correlation spectroscopy. Tretinoin, a lipophilic anti-acne agent was incorporated into SLN as a model drug. The encapsulation efficiency of tretinoin in the SLN was determined by using Nanosep ultrafilteration device at different lipid loads viz. 1%, 1.5% and 2%. Glyceryl monostearate SLN fabricated from biocompatible microemulsion template exhibited average particle size of 175 nm and polydispersity index of 0.833. Tretinoin could be successfully incorporated into SLN and the encapsulation efficiency ranged from 37-48% at different lipid loads.

Successful Retrial of ECT Two Months After ECT-Induced Takotsubo Cardiomyopathy

heart failure; however, recovery of cardiac function is often complete within the first week following the insult. Cardiac enzymes may be mildly elevated, but on cardiac catheterization there is usually no evidence of coronary artery disease, or only "mild luminal irregularities" may be noted (7). Contraction band necrosis may be seen on biopsy in the more serious cases. The cause of takotsubo cardiomyopathy is unknown, but several mechanisms have been suggested, including ischemia from coronary artery spasm, microvascular spasm, and direct myocyte injury (5).

New Drugs for Epidural Analgesia

In recent years there has been a wide use of the epidural technique not only during surgery to provide anesthesia and analgesia, but also for obstetric and trauma as well as acute, chronic and cancer pain states. Nowadays there is an increase in the number of the epidural drugs. Local anesthetics and opioids are still the pharmacological agents more widely used epidurally, nevertheless other drugs from different pharmacological classes are administered as adjuvant to local anesthetics and opioids or are in various early stages of investigation. Regarding to local anesthetics, the most recent literature focuses on the new enantiomers, ropivacaine and levobupivacaine, the efficacy of which is similar to that of bupivacaine with a reduced risk of cardiotoxicity. About opioids, the other class of drugs mainly used, the debate, in the last years, concerned the physicochemical properties of morphine and of the more recent lipophilic agents, fentanyl and sufentanil, in order to explain the main differences in efficacy and safety. Other categories of agents have been investigated for epidural administration, such as alpha(2)-adrenergic agonists clonidine and dexmedetomidine. They are being used increasingly as adjuvants to local anesthetics and opioids. Ketamine and neostigmine, the more recent studied drugs for epidural use, are still under investigation and are not part of routine clinical practice.

0277: Ultrasound Mediated Drug Delivery

Echogenic liposomes (ELIP) are under development to enable ultrasound-controlled drug delivery. Ultrasound-triggered release of hydrophilic and lipophilic agents from circulating ELIP in vitro using 6-MHz color Doppler ultrasound will be reviewed. The differential efficiency of ultrasound-mediated pharmaceutical release from ELIP for hydrophilic and lipophilic compounds suggests that hydrophilic drugs are better candidates for the design and development of ultrasound-controlled drug delivery systems. Optimal ultrasound parameters to enhance delivery of therapeutic-loaded ELIP into an artery are also being developed for the treatment of atherosclerosis. The aim of this work was to determine whether anti-ICAM-targeted, Rhodamine-labeled ELIP (Rh-ELIP) would adhere to and penetrate the vascular endothelium in atheromatous murine arterial segments with intravascular flow treated with 1-MHz continuous wave ultrasound (CW US). A broadband focused hydrophone, confocally aligned with the artery and 1-MHz transducer field was used as a passive cavitation detector (PCD). Arteries were insonified with 1-MHz CW US (0.49 MPa peak-to-peak pressure) and the PCD was used to verify the duration of the resulting stable cavitation. The perivascular saline was collected and analyzed spectrofluorometrically for the presence of Rh-ELIP. Arteries were prepared for histological analysis by a pathologist blinded to the exposure conditions. Arteries exposed to Rh-labeled ELIP and 1-MHz US exhibited greater adherence of Rh-ELIP to the vascular endothelium, and greater passage of Rh-ELIP across the vessel wall. No damage was detected in any of the arteries on histology. These studies will aid in the development of a strategy for improving atheroma treatment without causing ultrasound-related tissue damage. Echogenic liposomes (ELIP) are under development to enable ultrasound-controlled drug delivery. Ultrasound-triggered release of hydrophilic and lipophilic agents from circulating ELIP in vitro using 6-MHz color Doppler ultrasound will be reviewed. The differential efficiency of ultrasound-mediated pharmaceutical release from ELIP for hydrophilic and lipophilic compounds suggests that hydrophilic drugs are better candidates for the design and development of ultrasound-controlled drug delivery systems. Optimal ultrasound parameters to enhance delivery of therapeutic-loaded ELIP into an artery are also being developed for the treatment of atherosclerosis. The aim of this work was to determine whether anti-ICAM-targeted, Rhodamine-labeled ELIP (Rh-ELIP) would adhere to and penetrate the vascular endothelium in atheromatous murine arterial segments with intravascular flow treated with 1-MHz continuous wave ultrasound (CW US). A broadband focused hydrophone, confocally aligned with the artery and 1-MHz transducer field was used as a passive cavitation detector (PCD). Arteries were insonified with 1-MHz CW US (0.49 MPa peak-to-peak pressure) and the PCD was used to verify the duration of the resulting stable cavitation. The perivascular saline was collected and analyzed spectrofluorometrically for the presence of Rh-ELIP. Arteries were prepared for histological analysis by a pathologist blinded to the exposure conditions. Arteries exposed to Rh-labeled ELIP and 1-MHz US exhibited greater adherence of Rh-ELIP to the vascular endothelium, and greater passage of Rh-ELIP across the vessel wall. No damage was detected in any of the arteries on histology. These studies will aid in the development of a strategy for improving atheroma treatment without causing ultrasound-related tissue damage.

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Statins Lower AD Risk, Despite Allele Status

Statins Lower AD Risk, Despite Allele Status

Influence of Borneol on In Vitro Corneal Permeability and on In Vivo and In Vitro Corneal Toxicity

This study examined whether borneol could enhance corneal drug permeability. Model drugs containing either synthetic or natural borneol were co-administered to isolated intact or de-epithelialized rabbit corneas and the apparent permeability coefficients were measured. Draize tests in rabbits and levels of isolated intact rabbit corneal hydration were used to measure in vivo and in vitro toxicity, respectively. Synthetic borneol (0.1%) increased corneal penetration of the lipophilic agents, indomethacin and dexamethasone, by 1.23 and 2.40, respectively, and of the hydrophilic agents, ofloxacin, ribavirin and tobramycin, by 1.87, 2.80 and 3.89, respectively. For natural borneol, the corresponding fold increases were 1.67, 2.00, 2.15, 2.18 and 3.39, respectively. Removing the epithelium attenuated the penetration-enhancing effects of borneol. Borneol (0.1%) did not damage corneal tissue. The ability of borneol to enhance drug penetration through the outer corneal layer, particularly for highly-hydrophilic drugs, suggests that further clinical investigation may be warranted.

Liposomes in dermatology today

Liposomes are vesicles consisting of spherical phospholipid bi-layers with specific properties making them useful for topical application of drugs. Liposome research has expanded considerably over the last 30 years and nowadays, it is possible to construct a wide range of liposomes varying in size, phospholipids composition and surface characteristics to suit the specific application for which they are intended. In dermatology, the topical application of liposomes has proven to be of therapeutic value. Liposomes can be used as carriers for hydrophilic as well as lipophilic therapeutic agents because of their amphipathic character. They may improve stabilization of instable drugs by encapsulating them and serve as penetration enhancers facilitating the transport of compounds that otherwise cannot penetrate the skin. Liposomes help in reducing skin irritation by sustaining the release of drugs and by hydration of the epidermis. They also have the potential to target drugs into the pilosebaceous structures and hence they have an additional advantage for treatment of hair follicle-associated disorders. Clinical data indicate that 5-ALA encapsulated in liposomes improves the quality of Fluorescence Diagnosis by ALA-induced Porphyrins (FD) and optimizes the results of Photodynamic Therapy (PDT).

99mTc sestamibi imaging

Hepatobiliary scintigraphy is an integral part in the diagnostic work-up of the neonatal cholestasis syndrome. However, less than optimal specificity is its major disadvantage. Differentiation between biliary atresia and neonatal hepatitis is nearly impossible in some cases with poor hepatocellular function. 99mTc sestamibi (MIBI) is a cationic lipophilic agent which is a substrate of P-glycoprotein. This glycoprotein is normally expressed in biliary canalicular surfaces of hepatocytes. This property provides a hepatic excretory mechanism which is different from bilirubin excretion. In this study we evaluated the value of 99mTc MIBI in differential diagnosis of neonatal cholestasis. 20 infants with a mean age of 2.41 months (range, 0.1-5 months) were included in the study. Ten infants turned out to have extrahepatic biliary atresia and the other ten had neonatal hepatitis. Hepatobiliary (with 99mTc BrIDA) and 99mTc MIBI scintigraphy were performed for all the patients. 99mTc MIBI scintigraphy has shown bowel activity in all patients, including the patients with biliary atresia. Hepatobiliary scintigraphy revealed bowel activity only in five patients with neonatal hepatitis. Bowel visualization with 99mTc MIBI may be seen in patients with biliary atresia and 99mTc MIBI has limited value in differential diagnosis of neonatal cholestasis.

The effects of lipophilic substances on the shape of erythrocytes demonstrated by a new in vitro-method

Low aqueous solubility of lipophilic agents, such as free fatty acids, hampers proper in vitro demonstration of biological effects, yielding an ambiguous in vitro–in vivo correlation. We have therefore developed a method for evaluating the acute effects of lipophilic substances on the shape of erythrocytes and estimated EC 50 and Hill coefficient according to the sigmoidal E max model. The test substance dissolved in medium-chain triglyceride is coated on a polycarbonate slide which serves as a cover sheet of a Bürker chamber. Freshly collected finger-tip blood is diluted with autologous EDTA–plasma and introduced into the chamber. After 10 min at 37 °C, the cells are photographed under microscope and the fractions of normal and defect cells are evaluated. No staining is needed and the cells are kept viable during the test period. With increasing chain length, fatty acids, aliphatic amines and alcohols all increased the fraction of defect erythrocytes in a concentration-dependent manner. The results indicate that several fatty acids are very potent in their acute actions on erythrocytes, and that this effect is due to chain length rather than conformation. Conclusion The technique offers a screening method for testing the harmful effects of small amounts of lipophilic substances on erythrocytes.

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

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. Calcein, a hydrophilic agent, and papaverine, a lipophilic agent, were each separately loaded into ELIPs. Calcein-loaded 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. 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 C-ELIPs and P-ELIPs (P < .05). The differential efficiency of ultrasound-mediated 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.