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Biomedical subjects

Theresa M Allen

Publications and source records attributed to Theresa M Allen.

At least 19 recordsLinked to original sources
PubMed2006

Targeting liposomal chemotherapy via both tumor cell-specific and tumor vasculature-specific ligands potentiates therapeutic efficacy.

Neuroblastoma, the most common solid tumor of infancy derived from the sympathetic nervous system, continues to present a formidable clinical challenge. Sterically stabilized immunoliposomes (SIL) have been shown to enhance the selective localization of entrapped drugs to solid tumors, with improvements in therapeutic indices. We showed that SIL loaded with doxorubicin (DXR) and targeted to the disialoganglioside receptor GD(2) [aGD(2)-SIL(DXR)] led to a selective inhibition of the metastatic growth of experimental models of human neuroblastoma. By coupling NGR peptides that target the angiogenic endothelial cell marker aminopeptidase N to the surface of DXR-loaded liposomes [NGR-SL(DXR)], we obtained tumor regression, pronounced destruction of the tumor vasculature, and prolonged survival of orthotopic neuroblastoma xenografts. Here, we showed good liposome stability, long circulation times, and enhanced time-dependent tumor accumulation of both the carrier and the drug. Antivascular effects against animal models of lung and ovarian cancer were shown for formulations of NGR-SL(DXR). In the chick embryo chorioallantoic assay, NGR-SL(DXR) substantially reduced the angiogenic potential of various neuroblastoma xenografts, with synergistic inhibition observed for the combination of NGR-SL(DXR) with aGD(2)-SIL(DXR). A significant improvement in antitumor effects was seen in neuroblastoma-bearing animal models when treated with the combined formulations compared with control mice or mice treated with either tumor- or vascular-targeted liposomal formulations, administered separately. The combined treatment resulted in a dramatic inhibition of tumor endothelial cell density. Long-term survivors were obtained only in animals treated with the combined tumor- and vascular-targeted formulations, confirming the pivotal role of combination therapies in treating aggressive metastatic neuroblastoma.

Animals↗
PubMed2006

The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis.

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are major phospholipids in mammalian membranes. In liver, PC is synthesized via the choline pathway or by methylation of PE via phosphatidylethanolamine N-methyltransferase (PEMT). Pemt(-/-) mice fed a choline-deficient (CD) diet develop rapid steatohepatitis leading to liver failure. Steatosis is observed in CD mice that lack both PEMT and multiple drug-resistant protein 2 (MDR2), required for PC secretion into bile. We demonstrate that liver failure in CD-Pemt(-/-) mice is due to loss of membrane integrity caused by a decreased PC/PE ratio. The CD-Mdr2(-/-)/Pemt(-/-) mice escape liver failure by maintaining a normal PC/PE ratio. Manipulation of PC/PE levels suggests that this ratio is a key regulator of cell membrane integrity and plays a role in the progression of steatosis into steatohepatitis. The results have clinical implications as patients with nonalcoholic steatohepatitis have a decreased ratio of PC to PE compared to control livers.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Chemosensitization of carcinoma cells using epithelial cell adhesion molecule-targeted liposomal antisense against bcl-2/bcl-xL.

Nanoscale drug delivery systems, such as sterically stabilized immunoliposomes binding to internalizing tumor-associated antigens, can increase therapeutic efficacy and reduce toxicity to normal tissues compared with nontargeted liposomes. The epithelial cell adhesion molecule (EpCAM) is of interest as a ligand for targeted drug delivery because it is abundantly expressed in solid tumors but shows limited distribution in normal tissues. To generate EpCAM-specific immunoliposomes for targeted cancer therapy, the humanized single-chain Fv antibody fragment 4D5MOCB was covalently linked to the exterior of coated cationic liposomes. As anticancer agent, we encapsulated the previously described antisense oligonucleotide 4625 specific for both bcl-2 and bcl-xL. The EpCAM-targeted immunoliposomes (SIL25) showed specific binding to EpCAM-overexpressing tumor cells, with a 10- to 20-fold increase in binding compared with nontargeted control liposomes. No enhanced binding was observed on EpCAM-negative control cells. On cell binding, SIL25 was efficiently internalized by receptor-mediated endocytosis, ultimately leading to down-regulation of both bcl-2 and bcl-xL expression on both the mRNA and protein level, which resulted in enhanced tumor cell apoptosis. In combination experiments, the use of SIL25 led to a 2- to 5-fold sensitization of EpCAM-positive tumor cells of diverse origin to death induction by doxorubicin. Our data show the promise of EpCAM-specific drug delivery systems, such as antisense-loaded immunoliposomes, for targeted cancer therapy.

Antibiotics, Antineoplastic↗
PubMed2006

Pharmacokinetics and pharmacodynamics of lipidic nano-particles in cancer.

Nanoscale drug delivery systems (DDS) are used to circumvent some of the non-ideal properties of conventional anticancer chemotherapy drugs. Manipulation of the physical properties of DDS provides improved control over the pharmacokinetics (PK) and pharmacodynamics (PD) of the encapsulated drugs relative to free drugs. Liposomes are the archetypical nanoscale DDS and the first of these received clinical approval in 1990. DOXIL, liposomal doxorubicin, was the first commercially available liposomal anticancer drug (1995). It has an enhanced circulation half-life compared to the free drug because of its surface-grafted polyethylene glycol coating. DOXIL passively targets solid tumors, and once the liposomes localize in the tumor interstitial space, the cytotoxic drug is slowly released within the tumor. Liposomes can act as sustained release delivery system and manipulation of properties such as, liposome diameter, drug release rate, bioavailability and dosing schedule can significantly impact the therapeutic outcome of the liposomal drugs. This review will focus on how alteration of these properties can impact the therapeutic efficacy and side effect profiles of DDS.

Animals↗
PubMed2005

Determination of doxorubicin levels in whole tumor and tumor nuclei in murine breast cancer tumors.

PURPOSE: Pharmacokinetic studies on liposomal drugs have previously measured total drug levels in tumors, which include non-bioavailable drug. However, drugs must be released from liposomes to have activity. We have developed a method for measuring levels of bioavailable (released) doxorubicin in vivo in tumors that will allow therapeutic activity to be correlated with bioavailable drug levels. EXPERIMENTAL DESIGN: Mice orthotopically implanted with mammary carcinoma (4T1) were injected i.v. 10 days after implantation with free doxorubicin or formulations of liposomal doxorubicin with different drug release rates. Tumors were excised at various times after injection, and total tumor doxorubicin levels were determined by acidified isopropanol extraction of whole tumor homogenates. Bioavailable doxorubicin levels were determined by extraction of doxorubicin from isolated tumor nuclei. RESULTS: Free doxorubicin had high levels of bioavailability in tumor tissue; 95% of the total doxorubicin in tumors was bound to nuclear DNA by 24 hours after injection. Administration of Doxil, a slow release liposomal formulation of doxorubicin, gave an area under the time-versus-concentration curve (AUC) for total doxorubicin 7 days after injection that was 87-fold higher than that obtained for free doxorubicin, and 49% of the liposomal doxorubicin was bioavailable. For liposomes with a more rapid doxorubicin release rate, by 7 days after injection, the AUC(0-7 days) for total doxorubicin was only 14-fold higher than that for free doxorubicin and only 27% of liposomal doxorubicin was bioavailable. CONCLUSIONS: This technique allows correlations to be made between drug bioavailability and therapeutic activity and will help in the rational design of drug carriers.

Animals↗
PubMed2005

Distribution of photosensitizers in bladder cancer spheroids: implications for intravesical instillation of photosensitizers for photodynamic therapy of bladder cancer.

PURPOSE: Uniform intratumor distribution of sufficient photosensitizer is one of the important aspects of photodynamic therapy for solid tumors. METHODS: Multicellular spheroids derived from a human transitional cell carcinoma cell line (MGHU3) were used as a surrogate system of tiny solid tumors to study intratumor distribution of photosensitizers. Photosensitizers included Photofrin, hypocrellins (HBEA-R1/R2, HBBA-R2), aluminum phthalocyanine chloride (AlPC), benzoporphyrin derivative monoacid ring A (BPD-MA), protoporphyrin-IX (PpIX), and liposomal formulations of HBBA-R2 and BPD-MA. Spheroids were incubated with various doses of the above drugs for 1-4 hours, and were examined by confocal microscopy. RESULTS: Histology showed all cells were healthy in spheroids less than 400 microm in diameter. Scanning electron microscopy showed tight cell-to-cell interdigitation in spheroids. HBEA-R1/R2 distributed more uniformly in spheroids than other drugs. Free hypocrellins and BPD-MA penetrated spheroids centripetally deeper than AlPC, Photofrin, and PpIX. Liposomal HBBA-R2 and BPD-MA penetrated less than their free formulations. CONCLUSIONS: The spheroids mimic solid tumors prior to neovascularization. Based on drug distribution in spheroids, hypocrellins and BPD-MA appear superior to Photofrin, AlPC and PpIX for intravesical administration for bladder cancer phototherapy.

Administration, Intravesical↗
PubMed2005

Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates.

Some formulations of liposomal doxorubicin with intermediate rates of drug release have shown increased levels of toxicity in mice. Because antibody-mediated targeting of liposomal drugs influences the pharmacokinetics, mechanism of uptake, and selectivity of the associated drugs, we hypothesized that anti-CD19-mediated targeting of liposomal doxorubicin might moderate the toxicity of the problem formulations. Phosphatidylcholine/cholesterol liposomal formulations of doxorubicin having faster, intermediate, and slower drug release rates were prepared by altering the fatty acyl chain length or degree of saturation of the phosphatidylcholine component. Pharmacokinetic and biodistribution studies and in vivo drug release rates were determined in mice using liposomes dual labeled with [3H]cholesteryl hexadecylether and [14C]doxorubicin. Therapeutic studies were done in xenograft models of human B lymphoma (Namalwa cells). The rate of clearance of the liposomal lipid was similar for all formulations (average t1/2, 18 hours), but the rate of clearance of doxorubicin was dependent on the release rate of the formulation (t1/2, 2-315 hours). Liposomes with the slowest drug release rates showed no toxicity and exhibited therapeutic activity that was superior to the other formulations when targeted with anti-CD19; liposomes with the most rapid drug release rates also showed no toxicity but showed little therapeutic effect even when targeted. Liposomes with intermediate drug release rates exhibited varying degrees of toxicity. The toxicities could be reduced and even overcome by targeting with anti-CD19 antibodies. For these formulations, therapeutic effects were intermediate between those found for liposomes with the fastest and slowest drug release rates.

Animals↗
PubMed2005

Comparative evaluation of two purification methods of anti-CD19-c-myc-His6-Cys scFv.

Different chromatographic methods have been used to purify bacterially expressed single chain antibodies in soluble or insoluble form. Here, we compared two methods for purification of anti-CD19-c-myc-His6-Cys scFv expressed in Escherichia coli as soluble protein. The protein-L-agarose purification method is a one step purification method that yielded significant amounts of pure protein compared to the two-step Ni-NTA-agarose plus Resource 15S purification method. However, the protein-L purification method exhibited an additional lower molecular weight protein contaminant. Based on results from in vitro gel digestion, mass spectrometry and database search results, we confirmed that the lower molecular weight protein contaminant, which could not be purified by Ni-NTA-agarose and 15S column method, is a degraded product of the full length scFv construct.

Antibodies, Monoclonal↗
PubMed2005

Ligand-targeted liposomes for cancer treatment.

Selective targeting of ligand-targeted liposomes containing anticancer drugs or therapeutic genes to cell surface receptors expressed on cancer cells is a recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics or gene therapeutics. Some recent advances in the field of ligand-targeted liposomes for the treatment of cancer are summarized including: selection criteria for the receptors to be targeted, choice of targeting ligands and choice of encapsulated therapeutics. Targeting of liposomes to solid tumors, versus angiogenic endothelial cells versus vascular targets is discussed. Ligand-targeted liposomes have shown considerable promise in preclinical xenograft models and are poised for clinical development.

Animals↗
PubMed2004

Immune cell-mediated antitumor activities of GD2-targeted liposomal c-myb antisense oligonucleotides containing CpG motifs.

BACKGROUND: Expression of the c-myb proto-oncogene in neuroblastoma, the most common extracranial solid tumor of infancy, is linked with cell proliferation and differentiation. Neuroblastoma can be selectively targeted via monoclonal antibodies against the disialoganglioside (GD2) tumor-associated antigen. Liposomes coated with anti-GD2 antibodies (targeted liposomes) and entrapping a c-myb antisense oligonucleotide have antitumor activity. Because antisense oligonucleotides containing CpG motifs can stimulate immune responses, we evaluated the effect of CpG-containing c-myb antisense oligonucleotides encapsulated within targeted liposomes. METHODS: Antisense (myb-as) and scrambled (myb-scr) control oligonucleotides with CpG motifs were encapsulated within GD2-targeted and non-targeted liposomes. Two murine (nude and SCID-bg) xenograft models of neuroblastoma were established. Mice (groups of 10) were injected intravenously with various oligonucleotide and liposome formulations, and life span, long-term survival, immune cell activation, and cytokine release were measured over time. RESULTS: Tumor-bearing mice injected with targeted liposome-CpG-myb-as or targeted liposome-CpG-myb-scr lived longer than mice in any other group, although long-term survival (i.e., more than 120 days) was obtained only in mice injected with targeted liposome-CpG-myb-as. Splenocytes isolated from mice injected with targeted liposome-CpG-myb-as contained activated macrophages, B cells, and natural killer (NK) cells, but only activated NK cells were associated with antitumor cytotoxic activity. In vivo immune cell activation was accompanied by the time-dependent increases in plasma levels of the cytokines interleukin 12 (IL-12; maximum level reached by 2 hours) and interferon gamma (IFN-gamma; maximum level reached by 18 hours) and was dependent on the oligonucleotide CpG motif. Ablation of macrophages or NK cells resulted in a loss of in vivo antitumor activity. CONCLUSION: Immune cell activation, involving the time-dependent activation of macrophages and NK cells, contributes to the antitumor activity of targeted liposome-CpG-myb-as against neuroblastoma and could improve the effectiveness of antitumor targeted liposomes.

Animals↗
PubMed2004

Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer.

The pharmacokinetics (PK), biodistribution (BD), and therapeutic activity of pegylated liposomal doxorubicin formulations with different drug release rates were studied in an orthotopic 4T1 murine mammary carcinoma model. The focus of these experiments was to study the effects of different release rates on the accumulation of liposomal lipid and doxorubicin (DXR) into the tumor and cutaneous tissues of mice (skin and paws). These tissues were chosen because the clinical formulation of pegylated liposomal doxorubicin (Caelyx)/Doxi) causes mucocutaneous reactions such as palmar-plantar erythrodysesthesia (PPE). Liposomes with different doxorubicin (DXR) leakage rates were prepared by altering liposome fluidity through changing the fatty acyl chain length and/or degree of saturation of the phosphatidylcholine component of the liposome. Liposomes with fast, intermediate, and slow rates of drug release were studied. The plasma PK of the liposomal lipid was similar for all formulations, while the plasma PK of the DXR component was dependent on the liposome formulation. Liposomal lipid accumulated to similar levels in tumor and cutaneous tissues for all three formulations tested, while the liposomes with the slowest rates of DXR release produced the highest DXR concentrations in both cutaneous tissues and in tumor. Liposomes with the fastest drug release rates resulted in low DXR concentrations in cutaneous tissues and tumor. The formulation with intermediate release rates produced unexpected toxicity that was not related to the lipid content of the formulation. The liposomes with the slowest rate of drug leakage had the best therapeutic activity of the formulations tested.

Animals↗
PubMed2004

Improved outcome when B-cell lymphoma is treated with combinations of immunoliposomal anticancer drugs targeted to both the CD19 and CD20 epitopes.

PURPOSE: We have reported previously that successful immunoliposomal drug therapy with liposomal doxorubicin (DXR) against xenograft B-lymphoma models required targeting against an internalizing B-cell antigen, CD19 (P. Sapra and T. M. Allen. Cancer Res 2002;62:7190-4.). Here we compare targeting of immunoliposomal formulations of DXR with vincristine (VCR) targeted against CD19 versus a noninternalizing (CD20) epitope. We also examine the effect of targeting immunoliposomes with antibody combinations in an attempt to increase the total number of binding sites (apparent antigen density) at the target cell surface. EXPERIMENTAL DESIGN: Cell association of immunoliposomes (CD19-targeted, CD20-targeted, or combinations of the two) with human B-cell lymphoma (Namalwa) cells were studied using radiolabeled liposomes. Therapeutic efficacy of the same formulations was determined in a severe combined immunodeficient murine model. RESULTS: Therapeutic results in severe combined immunodeficient mice bearing Namalwa cells administered anti-CD20-targeted liposomal DXR were barely improved over those found for nontargeted liposomal DXR or free DXR but, surprisingly, administration of anti-CD20-targeted liposomal VCR resulted in a significantly improved therapeutic outcome compared with nontargeted liposomal VCR, free VCR, or anti-CD20-targeted liposomal DXR. Treatment of murine B lymphoma with single injections of combinations of anti-CD19- and anti-CD20-targeted liposomal VCR led to cures in 70% of mice. However, mice injected with similar combinations of liposomal DXR did not have improved survival rates over anti-CD19-targeted liposomal DXR by itself. CONCLUSIONS: The success of immunoliposomal therapy in combination regimens varies with the type of encapsulated drug and the nature of the target epitopes.

Animals↗
PubMed2004

Drug delivery systems: entering the mainstream.

Drug delivery systems (DDS) such as lipid- or polymer-based nanoparticles can be designed to improve the pharmacological and therapeutic properties of drugs administered parenterally. Many of the early problems that hindered the clinical applications of particulate DDS have been overcome, with several DDS formulations of anticancer and antifungal drugs now approved for clinical use. Furthermore, there is considerable interest in exploiting the advantages of DDS for in vivo delivery of new drugs derived from proteomics or genomics research and for their use in ligand-targeted therapeutics.

Biological Availability↗
PubMed2004

Improved therapeutic responses in a xenograft model of human B lymphoma (Namalwa) for liposomal vincristine versus liposomal doxorubicin targeted via anti-CD19 IgG2a or Fab' fragments.

PURPOSE: Monoclonal antibody-mediated targeting of liposomal anticancer drugs to surface antigens expressed on malignant B cells can be an effective strategy for treating B-cell malignancies. In a murine model of human B-cell lymphoma, we have made in vitro and in vivo comparisons of long-circulating sterically stabilized (Stealth) immunoliposome (SIL) formulations of two anticancer drugs, vincristine (VCR) and doxorubicin (DXR), with different mechanisms of action and drug release rates. EXPERIMENTAL DESIGN: SIL formulations of VCR or DXR were conjugated to the monoclonal antibody anti-CD19 (SIL[alphaCD19]) or its Fab' fragments (SIL[Fab']). Specific binding of SILs to Namalwa cells was studied using radiolabeled liposomes, and cytotoxicities of DXR- or VCR-loaded SILs were quantitated by a tetrazolium assay. Pharmacokinetic and drug leakage experiments were performed in mice using dual-labeled liposomes, and the therapeutic responses of SILs were evaluated in a Namalwa (human B lymphoma) cell xenograft model. RESULTS: SIL[alphaCD19] or SIL[Fab'] had higher association with and cytotoxicity against Namalwa cells than nontargeted liposomes. SIL[Fab'] had longer circulation times than SIL[alphaCD19], and VCR had faster release rates from the liposomes than DXR. SIL formulations of either VCR or DXR had significantly better therapeutic outcomes than nontargeted liposomes or free drugs. SILs loaded with VCR were superior to those loaded with DXR. SIL[Fab'] had better therapeutic outcomes than SIL[alphaCD19] for the drug DXR but were equally efficacious for the drug VCR. CONCLUSIONS: Treatment of a B lymphoma model with single injections of anti-CD19-targeted liposomal formulations of VCR resulted in high levels of response and long-term survivors. Responses to anti-CD19-targeted liposomal DXR were more modest, although the longer circulation times of SIL[Fab'] versus SIL[alphaCD19] led to superior therapeutics for DXR-loaded immunoliposomes.

Animals↗
PubMed2004

Pharmaco attributes of dioleoylphosphatidylethanolamine/cholesterylhemisuccinate liposomes containing different types of cleavable lipopolymers.

Various amounts of one of three different types of cleavable methoxy polyethylene glycol (mPEG)-phospholipids or of a non-cleavable counterpart (mPEG-DSPE) were included into pH-sensitive liposome formulations containing dioleoylphosphatidylethanolamine (DOPE) and cholesterylhemisuccinate (CHEMS) at a 6:4 molar ratio, and the effect on plasma clearance and contents release rates was determined. The cleavable lipopolymers were all based on a distearoylphosphatidyl lipid anchor, which was linked to mPEG via dithiodipropionateaminoethanol (mPEG-DTP-DSPE), dithio-3-hexanol (mPEG-DTH-DSPA), or Gly-Phe-Leu-Gly-aminoethanol (mPEG-GFLG-DSPE) linkers. In contrast to the first-generation thiolytically cleavable lipopolymer, mPEG-DTP-DSPE, the second generation conjugates contained a hindered disulfide or enzymatically cleavable tetrapeptide, respectively, as the points of scission. In the absence of mPEG-lipid, DOPE/CHEMS liposomes had rapid clearance half-lives. As the mol% of mPEG-lipid in the liposomes increased, the rate of clearance of DOPE/CHEMS liposomes in mice decreased. Zeta-potential measurements showed that decreased clearance was correlated with a decrease in the apparent surface charge of the liposomes, which approached neutrality as the content of mPEG-lipids increased to above 15 mol%. At these levels, liposomes containing mPEG-DTP-DSPE were cleared from blood circulation faster than liposomes containing other, less vulnerable lipopolymers. Liposomes with the peptide-linked lipopolymer exhibited the slowest clearance. The presence of either cleavable or non-cleavable mPEG-lipids at concentrations of 5 mol% or higher in the DOPE/CHEMS liposomes inhibited the release of doxorubicin from these liposomes in response to acid pH.

Animals↗
PubMed2004

Advantages of liposomal delivery systems for anthracyclines.

Liposomes, closed vesicular structures consisting of one or more lipid bilayers, have generated a great deal of interest as drug delivery vehicles. In particular, they have been investigated for their ability to improve the delivery of chemotherapeutic agents to tumors, in efforts to increase therapeutic efficacy and decrease toxicity to normal cells. Development of liposomal chemotherapeutic agents has, in the past, been hindered primarily by the rapid uptake of liposomes by the reticuloendothelial system. Numerous strategies that seek to either exploit or avoid this phenomenon have been used. As a result, several liposomal chemotherapeutic agents are now available in the clinic. STEALTH, a novel liposomal system coated with polyethylene glycol, avoids uptake by the reticuloendothelial system, thus improving drug delivery to the tumor while decreasing toxicity. In pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), this delivery system encapsulates doxorubicin within polyethylene glycol-coated liposomes, leading to promising new applications for a well-established drug. Liposome-encapsulated doxorubicin citrate complex (Myocet [NPLD]), another liposomal delivery system for doxorubicin, lacks the polyethylene glycol coating, resulting in much shorter circulation times than those of PLD. Daunorubicin citrate liposome (DaunoXome [DNX]) contains daunorubicin encapsulated in a smaller liposome of a different lipid composition. It has circulation times between those of PLD and NPLD. This article reviews the advantages of liposomal delivery systems in general and the divergent approaches that have been taken in developing these agents.

Anthracyclines↗
PubMed2004

Transendothelial movement of liposomes in vitro mediated by cancer cells, neutrophils or histamine.

A two-chamber culture system has been used to examine the ability of small liposomes to cross an endothelial cell barrier in response to various stimuli. Transendothelial transit of liposomes was almost negligible in the presence of intact, healthy endothelial cells (EC). Addition of histamine induced a concentration-dependent increase in the movement of liposomes across the EC monolayer. In the presence of polymorphonuclear neutrophils (PMNs), migrating in response to a chemotactic gradient of N-Formil-Met-Leu-Phe (fMLP), both liposomes and IgG crossed EC monolayer by a paracellular pathway, largely independent of an association with the PMNs. The presence of cancer cell, growing in the lower chamber or the presence of cancer cell-conditioned media, also resulted in the passage of liposome across the EC. We conclude that EC monolayers are sufficiently disrupted by several physiologically relevant stimuli to allow for the transendothelial passage of liposomes. These results have important implications for the therapeutic use of liposome in the treatment of cancer or other inflammatory processes.

Animals↗