RESUMO
PURPOSE: The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors. METHODS: 111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4-8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72 h at 4-6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72 h post-injection. RESULTS: 111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7-3.8% ID/cm3 in the tumors at approximately 24 h post-injection and mean tumor/muscle ratios in the range of 3.2-6.2 between 24 and 72 h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72 h post-injection showed 1.3-2.5% ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9-9.4. CONCLUSION: 111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.
RESUMO
The objective of this study was to evaluate the suitability of the bioadhesive polymers Carbopol 981 NF, Carbopol 1382 and sodium alginate as possible carriers for films for buccal drug delivery. Films were prepared by casting and solvent evaporation method, using propylene glycol as plasticizer and hydoxypropylmethyl cellulose to modify the properties of the films. The bioadhesive and mechanical properties of the films were evaluated with a TA-XT2i Texture Analyser. The alginate films exhibited greater bioadhesion and showed higher tensile strength and elasticity than the Carbopol films. There was a marked difference in the way the polymeric films hydrated in simulated saliva solution. Upon swelling the diameter of the alginate films did not increase but their thickness increases slightly, however the surface area of the Carbopol films increased significantly which points to them being unsuitable for drug delivery to the buccal mucosa. Excessive hydration of a polymeric film for buccal delivery could lead to decreasing adhesive strength and possibly loss of adhesion and hence shorter duration of retention. HPMC appeared to improve the properties of the films, affecting the bioadhesiveness and increasing tensile strength. For the alginate films an increase in HPMC leads to an increase in elasticity but for the Carbopol polymers this was not the case. The release profile of a model drug, sumatriptan succinate, showed that drug release was by diffusion rather than due to disintegration of the films. The results indicate that sodium alginate may be a suitable carrier for polymeric films for use in the buccal cavity.
