Anti-EGFR immunoliposomes for cabazitaxel delivery: From formulation development to in vivo evaluation in prostate cancer xenograft model.

Liposomes functionalized with monoclonal antibodies offer targeted therapy for cancer, boasting advantages like sustained drug release, enhanced stability, passive accumulation in tumors, and interaction with overexpressed receptors on cancer cells. This study aimed to develop and characterize anti-EGFR immunoliposomes loaded with cabazitaxel and assess their properties against prostate cancer in vitro and in vivo. Using a Box-Behnken design, a formulation with soy phosphatidylcholine, 10% cholesterol, and a 1:20 drug-lipid ratio yielded nanometric particle size, low polydispersity and high drug encapsulation. Immunoliposomes were conjugated with cetuximab through DSPE-PEG-Maleimide lipid anchor. Characterization confirmed intact antibody structure and interaction with EGFR receptor following conjugation. Cabazitaxel was dispersed within the liposomes in the amorphous state, confirmed by solid-state analyses. In vitro release studies showed slower cabazitaxel release from immunoliposomes. Immunoliposomes had enhanced cabazitaxel cytotoxicity in EGFR-overexpressing DU145 cells without affecting non-tumor L929 cells. Cetuximab played an important role to improve cellular uptake in a time-dependent fashion in EGFR-overexpressing prostate cancer cells. In vivo, immunoliposomes led to significant tumor regression, improved survival, and reduced weight loss in xenograft mice. While cabazitaxel induced leukopenia, consistent with clinical findings, histological analysis revealed no evident toxicity. In conclusion, the immunoliposomes displayed suitable physicochemical properties for cabazitaxel delivery, exhibited cytotoxicity against EGFR-expressing prostate cancer cells, with high cell uptake, and induced significant tumor regression in vivo, with manageable systemic toxicity.

Evaluating ternary systems with oligosaccharides as a strategy to improve the biopharmaceutical properties of furosemide.

Novel ternary systems with ß-cyclodextrin or maltodextrin and triethanolamine as the third component were developed with the aim of improving the oral bioavailability of furosemide. These new solids were characterized by solid-state nuclear magnetic resonance, Fourier transform infrared and Raman spectroscopy, X-ray powder diffractometry, scanning electron microscopy, thermogravimetric analysis, and differential scanning calorimetry. The solubility, dissolution and stability (chemical and physical) were studied. Among the most important results, it was observed that both ternary systems showed an important enhancement in the solubility of the drug. In particular, the system obtained by combination of ß-cyclodextrin and TEA exhibited improvement in the dissolution profiles and photo-stability of furosemide compared with the binary system previously reported. Moreover, this system constitutes an interesting therapeutic alternative as it did not produce cellular toxicity compared with free furosemide. In conclusion, the results obtained revealed that this ternary system establishes a promising approach for oral delivery of the drug.

Stability of Ceftazidime Pentahydrate Investigated by Thermal Analysis Techniques.

Cephalosporins are among the most frequently used broad-spectrum antimicrobial agents. Ceftazidime is a semisynthetic ß-lactam antibiotic for parenteral administration widely used in the clinical practice, which has been categorized as a third-generation cephalosporin antibiotic. This drug crystallizes as a pentahydrate and, as all cephalosporins, it is unstable and subject to hydrolytic degradation. Taking this into account, this study investigates the stability under 2 different conditions (high temperature and exposition to vacuum) by using various techniques, as thermal analysis, Raman spectroscopy, and X-ray powder diffraction supported by multivariate curve resolution. It was proved that ceftazidime pentahydrate is unstable under the studied variables, exhibiting several transformation processes, which were discussed in terms of the crystalline structure.

The design of novel metronidazole benzoate structures: exploring stoichiometric diversity.

The use of supramolecular synthons as a strategy to control crystalline structure is a crucial factor in developing new solid forms with physicochemical properties optimized by design. However, to achieve this objective, it is necessary to understand the intermolecular interactions in the context of crystal packing. The feasibility of a given synthon depends on its flexibility to combine the drug with a variety of coformers. In the present work, the imidazole-hydroxy synthon is investigated using as the target molecule benzoylmetronidazole [BZMD; systematic name 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl benzoate], whose imidazole group seems to be a suitable acceptor for hydrogen bonds. Thus, coformers with carboxylic acid and phenol groups were chosen. According to the availability of binding sites presented in the coformer, and considering the proposed synthon and hydrogen-bond complementarity as major factors, different drug-coformer stoichiometric ratios were explored (1:1, 2:1 and 3:1). Thirteen new solid forms (two salts and eleven cocrystals) were produced, namely BZMD-benzoic acid (1/1), C13H13N3O4·C7H6O2, BZMD-ß-naphthol (1/1), C13H13N3O4·C10H8O, BZMD-4-methoxybenzoic acid (1/1), C13H13N3O4·C8H8O3, BZMD-3,5-dinitrobenzoic acid (1/1), C13H13N3O4·C7H4N2O6, BZMD-3-aminobenzoic acid (1/1), C13H13N3O4·C7H7NO2, BZMD-salicylic acid (1/1), C13H13N3O4·C7H6O3, BZMD-maleic acid (1/1) {as the salt 1-[2-(benzoyloxy)ethyl]-2-methyl-5-nitro-1H-imidazol-3-ium 3-carboxyprop-2-enoate}, C13H14N3O4+·C4H3O4-, BZMD-isophthalic acid (1/1), C13H13N3O4·C8H6O4, BZMD-resorcinol (2/1), 2C13H13N3O4·C6H6O2, BZMD-fumaric acid (2/1), C13H13N3O4·0.5C4H4O4, BZMD-malonic acid (2/1), 2C13H13N3O4·C3H2O4, BZMD-2,6-dihydroxybenzoic acid (1/1) {as the salt 1-[2-(benzoyloxy)ethyl]-2-methyl-5-nitro-1H-imidazol-3-ium 2,6-dihydroxybenzoate}, C13H14N3O4+·C7H5O4-, and BZMD-3,5-dihydroxybenzoic acid (3/1), 3C13H13N3O4·C7H6O4, and their crystalline structures elucidated, confirming the robustness of the selected synthon.