3/22/2023 0 Comments Remove attachment tamer mac![]() ![]() ![]() Still, Doxil ® is responsible for some non-specific toxicity (cardiomyopathy and myelosuppression) 11, 12, and additionally provokes certain mucocutaneous reactions 12, 13. The encapsulation of doxorubicin into PEG-liposomes has not only increased the tumor concentration of the drug via the EPR effect, but also decreased its volume of distribution, and consequently the therapy-associated toxicity. Doxil ®/Caelyx ® is also in phase II clinical trials for patients with squamous cell cancer of head and neck and ovarian cancer 2. The effective delivery of doxorubicin in PEG-liposomes (Doxil ®/Caelyx ®) in the treatment of solid tumors in patients with breast-carcinoma metastases has resulted in a marked increase in survival 2, 10. Clinically, EPR (“passively”)-targeted PEG-liposomes have been successfully used to deliver doxorubicin to skin, cervical or breast cancers and have been shown to enhance therapeutic activity compared with the same drug administered in the free form or entrapped in conventional liposomes 6, 8, 9. Thus, Doxil ® demonstrates decreased cardiotoxicity and improved tumor accumulation via the enhanced permeability and retention (EPR) mechanism 6, 7. The use of the liposomal carrier allows for decreased side effects of cancer chemotherapeutics, such as non-specific toxicity, and for enhanced drug delivery into tumors 4, 5. Liposomal formulations of various anticancer drugs are widely used in experimental and clinical oncology with some of them, such as Doxil ® (doxorubicin incorporated into long-circulating PEGylated liposomes), becoming drugs of choice under certain conditions 1 – 3. Our results clearly show the remarkable capability of 2C5-targeted Doxil ® to specifically deliver its cargo into various tumor manifestations (solid and metastatic) significantly increasing the efficacy of therapy. Targeted doxorubicin-loaded PEG-liposomes were significantly more effective in inhibiting tumor growth and metastatic process in the LLC tumor models in mice. 2C5 antibody-targeted liposomes demonstrate significantly enhanced accumulation in LLC tumors. ![]() Therapeutic action of various liposomal formulations was followed by registering primary tumor growth, determining tumor weigh upon mice sacrifice, and by counting the number of metastases in the liver and lungs. The pharmacokinetics of plain and immuno-targeted Doxil ®-mimicking liposomes, as well as their accumulation in primary Lewis Lung Carcinoma (LLC) tumors in mice was followed by real-time gamma-scintigraphy upon liposomal membrane labeling with 111In. Antibody coupling to PEGylated doxorubicin-liposomes was performed by the “post-insertion” technique. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded long-circulating liposomes (Doxil ®, ALZA Corp.) by coupling to their surface the anti-cancer monoclonal antibody 2C5 (mAb 2C5) with nuclesome (NS)-restricted activity, that can recognize the surface of various tumor but not normal cells via the surface-bound nucleosomes released from the apoptotically dying neighboring tumor cells and specifically targets pharmaceutical carriers to tumor cells in vitro and in vivo. (A full release was planned, but unfortunately never completed.The efficacy of drug delivery systems can be significantly enhanced by making them target-specific via the attachment of various ligands to their surface. You can get the pre-release build of Attachment Tamer that offers the most important Attachment Tamer functionality on OS X 10.9 Mavericks. Note: Further development has been halted. PS: If you are repeatedly getting a message about Attachment Tamer being disabled on OS X Yosemite, you can use the latest pre-release installer to remove it. As the holiday season has slowed us down, I am going announce more details early in the new year. I am preparing a solution for handling attachments in current and future OS X releases, that would be up to the standard set by previous Attachment Tamer releases, in a partnership with well-known Mac developers. After 10 years of continued work on Attachment Tamer and over a year of, admittedly, not being able to keep up with Apple's sped up release cycle and increasing technical difficulties of Mail plug-in development, I decided to find a better way forward for both my customers and myself. ![]()
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