Doxorubicin loaded with

Conjugation of a 2-nitroimidazole derivative to carboxymethyl dextran allowed doxorubicin-loading with hypoxia-induced cellular uptake and cytotoxicity in vitro [110]. The dextran group for stability in the circulation and primary tumor accumulation was combined with conversion from a hydrophobic 2-nitroimidazole to a hydrophilic 2-aminoimidazole under hypoxia to promote doxorubicin release in tumor environment. This system showed a 4-fold doxorubicin accumulation in tumor over liver, lung, spleen, kidney, and heart 24 h after systemic injection and enhanced anticancer activity in vivo over free drug. 

Freeze dried liposomes loaded with doxorubicin (DXR) have been stored for 6 months at temperatures between -20 and +50 °C. Up to 30 °C, no sign of degradation was found, but at 40 to 50 °C - well below T of the dried cake - the total DXR content and the retention of the drug after dehydration decreased, while the size of the liposomes increased jo a certain extent. The stability with RM below 1 % has been better than with 2.5-3.5 %. 

Figure 7 Release profiles of doxorubicin from the two nanoparticles free doxorubicin encapsulated nanoparticles and PLGA-doxorubicin loaded nanoparticles (adapted with permission from the publisher [24]).

For insertion into premade doxorubicin-loaded liposomes (Doxil), mix equal volumes of liposomes and lipidation reaction mixture and incubate at 37°C for 12-16 h (see Note 7). Purification of unreacted lipid and protein is not necessary at this step, because they do not interfere with insertion process and will be removed eventually by gel-filtration of decorated liposomes on Sepharose CL-4B. 

Figure 6.6 RGD peptide selectively enhances doxorubicin delivery by SWNTs and toxicity to integrin aT(33-positive cells, (a) Schematic structure of PL-SWNT-RGD-DOX, that is, SWNT functionalized with RGD at the termini of PEG and loaded with doxorubicin on the sidewall by ir-stacking.

These block-copolymers form micelles in aqueous solution with spherical core/shell structures and diameters around 20-40 nm (Figure 5.9). The hydrophobic core of these micelles can be loaded with a hydrophobic drug such as doxorubicin. After intravenous administration the micelles tend to accumulate at tumor sites and release the entrapped drug there. Some of the characteristics of these micellar systems are listed in Table 5.5. 

Poly(alkyl cyanoacrylate) nanoparticles accumulate in the liver (60-90% of the injected dose) and the spleen upon iv injection, with the macrophages in the liver being their major target. Nanoparticles loaded with doxorubicin have shown a markedly enhanced therapeutic index in a number of animal tumor models. 

The drug desorption kinetics is extremely important for application of the adsorbents as anti-cancer drug carriers. One milligram per milliliter of FC-4 particles were mixed with 100 pg/ml solution of doxorubicin, sonicated for 2 min and incubated on a shaker for 2.5 h. The particles were then sedimented in a centrifuge, the supernatant was removed, and the pellet of FC-4 loaded with doxorubicin was re-suspended in human blood serum at the same concentration as that of the initial doxorubicin solution. The mixture was incubated on a shaker at 37°C. Samples were taken at 6 h intervals for the first 3 days and daily thereafter, the adsorbent particles were removed by magnetic sedimentation and the optical density of the supernatant was measured at 296 nm. The concentration of the drug in solution was calculated. 

The superiority of doxorubicin targeted with the aid of poly(alkylcyanoacrylate) nanospheres was later confirmed in a murine hepatic metastases model (M5076 reticulosarcoma). Irrespective of the dose and the administration schedule, the reduction in the number of metastases was much greater with doxorubicin-loaded nanospheres than with free doxorubicin, particularly if treatment was given only when the metastases were... 

Lukyanov AN, Elbayoumi TA, Chakilam AR, Torchilin VP (2004) Tumor-targeted liposomes Doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody. J Control Release 100 135-144... 

Gupta B, Torchilin VP (2007) Monoclonal antibody 2C5-modified doxorubicin-loaded liposomes with significantly enhanced therapeutic activity against intracranial human brain U- 8 7 MG tumor xenografts in nude mice. Cancer Immunol Immunother 56 1215-1223... 

Targeted Magnetic Liposomes Loaded with Doxorubicin... 

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