.Oral administration of the nonsteroidal anti-estrogen tamoxifen is the treatment of choice for metastatic estrogen receptor-positive breast cancer. Tamoxifen shows a fairly good oral bioavailability combined with large interindividual variations and side effects. With the aim to improve tamoxifen bioavailability and to achieve the active dosage at tumour site for a long period we studied the in vitro activity of a tamoxifen formulation in calcium alginate/chitosan microparticles which were designed for the targeting to the gut-associated lymphoid tissue by means Peyer’parch uptake. Moreover, the influence of alginate mannuronic/glucuronic (M/G) ratio affecting a probable interaction with cationic drug was evaluated by comparing two types of sodium alginate (M/G = 62/38 and M/G = 30/70) for the microparticle preparation. MCF-7 and Vero cells were cultured in Eagle Minimum Essential Medium and treated with growing concentrations (from 10 to 100 M/ml medium) of tamoxifen alone, microparticles loaded with tamoxifen and microparticles alone as control. MTT test was performed on both the coltures. The results observed after 24, 48 and 72 hours showed that both the types of sodium alginate improved cell growth in a dose-dependent way. Tamoxifen LD50 values are similar (38M/ml) in Vero and MCF-7 cells only after a 24 h incubation time. The values we observed after 48 and 72 h showed a higher toxicity on Vero cells (LD50 = 10M/ml) with respect to MCF-7 cells (25M/ml). Interesting results came from the comparison between the two types of microparticles loaded with tamoxifen. Microparticles release the drug after 48 hours and LD50 are significantly changed both with respect to the drug alone and, in particular, to the type of alginate. When M/G 62/38 alginate is used LD50 was enhanced: 25M/ml on Vero coltures and 48M/ml on MCF-7 cells; when M/G 30/70 alginate is used, LD50 was reduced: 25M/ml on Vero cells and 10M/ml on MCF-7 cells thus showing a stronger activity of the formulation on both cells, but with a lower cytotoxicity on Vero cells. We concluded that these preliminary results confirm that the microparticle formulation of tamoxifen can be useful in improving its bioavailability. Moreover, we outline that the therapeutic dosages must be accurately evaluated in respect with the so-called inert molecules (excipients) employed in the formulation since their interaction ability with the active compound can dramatically change the drug activity and toxicity.
Role of the pharmaceutical excipients in the tamoxifen activity on MCF-7 and Vero cell cultures / Rossi, Tiziana; Iannuccelli, Valentina; Coppi, Gilberto; E., Bruni; Baggio, Giosuè Gabriele. - STAMPA. - ND:(2008), pp. 570-570. (Intervento presentato al convegno 8th International Conference of anticancer Research tenutosi a Kos nel 17/22 ottobre 2008).