Establishment and characterization of new murine breast cancer cell lines

The establishment of two new breast cancer cell lines, MXT+ and MXT-, derived from the murine breast cancer models MXT-M-3,2 MC (hormone-sensitive) and MXT-M-3,2 (ovex) MC (hormone-insensitive), is described. Characterization of the cell lines was performed by investigation of morphology, steroid hormone receptor state, growth kinetics, and drug response as well as by cytogenetic analysis. MXT+ contains estrogen receptors (ER; 6.9 fmol/mg protein) as well as progesterone receptors (PgR; 9.2 fmol/mg protein) and therefore is inhibited by tamoxifen (Tam). MXT- proved to be ER- but PgR+ (23.4 fmol/mg protein) and, as expected, resistant against Tam. The sensitivity of MXT+ and MXT- against a pattern of therapeutically established anti-breast cancer drugs (cDDP, cisplatin; JM-8, carboplatin; DX, adriamycin; 5-FU, 5-fluorouracil; MTX, methotrexate; VLB vinblastine) was studied by use of a computerized, kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. For each compound the inhibition profile reflecting cytostatic, transient cytotoxic, or cytocidal drug effects as well as development of resistance was evaluated. The following order of activity was found: MTX > VLB > or = DX > cDDP > or = 5-FU > JM-8. The test data of 5-FU, VLB, cDDP, and Tam on MXT+ as well as on MXT- were compared with those from studies on ER+ and ER- human breast cancer cell lines (MCF-7, ZR-75-1, T-47-D, and MDA-MB-231, respectively). They revealed comparable inhibition profiles and sensitivities of human and murine breast cancer cell lines, an indication that the results achieved in combined in vitro-/in vivo tests by use of the murine test models MXT+, MXT-, MXT-M-3,2 MC, and MXT-M-3,2(ovex) MC are relevant for therapy in humans

New environmental sensitive system for colon-specific delivery of peptidic drugs.

Nano and micro preparative technologies for the realization of pharmaceutical carriers represent an actual strategy for reaching the therapeutic success of drugs, particularly in the case of peptidic drugs. Vancomycin is here entrapped in carriers composed by a swellable, mucoadhesive and biodegradable albumin core, coated with fatty acids able to improve a colon-specific release. Bovine serum albumin nanospheres (core) were prepared from protein solutions using a coacervation method followed by thermal cross-linking at different temperature, or from protein solutions at different pHs using a coacervation method followed by thermal cross-linking at 75 degrees C. Solid nanospheres were collected by freeze-drying, loaded by soaking from solutions of vancomycin and subsequently coated with myristic, palmitic or stearic acid by spray-drying technique obtaining microcapsules. Nanosphere dimensions and polydispersity, drug loading capacity, swelling ability and mucoadhesion properties were evaluated, as well as in vitro release behaviour. The results indicated that nanospheres present an adequate loading capacity, a great swelling tendency and good mucoadhesion ability. Moreover, albumin cores showed a pH-dependent release according to the structure of thermally denaturated protein in different experimental conditions, while microcapsules showed a pH-dependent release according to the different fatty acids solubility in acidic and alkaline media