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The aim of the study was to develop and evaluate the efficacy of a functionalized layer-by-layer (LbL) assembled film entrapped with oxaliplatin (OX) and signal transducer and activator of transcription 3 (STAT3) siRNA in the localized treatment of colon cancer. The LbL film was prepared by the sequential layering of chitosan (CS) and alginate to attain desired physical and mechanical properties. The film was functionalized by coating folic acid-conjugated CS on one side. On the other side, polycaprolactone was coated as a backing layer to provide directional drug release. OX was entrapped within the layers of the film, while STAT3 siRNA was complexed with CS to form nanoparticles before entrapment in the LbL film. The CS–siRNA nanoparticles were taken up by the colon carcinoma, Caco-2 cells within 3 h and provided concentration-dependent reduction in STAT3 protein expression. The functionalized LbL film (F-LbL film) selectively adhered to the colon cancer tissue in the mice model, whereas the nonfunctionalized film adhered to the normal colon tissue. The combination of OX and STAT3 siRNA provided significantly greater tumor regression, survival rate, and STAT3 protein suppression after localized delivery through oral administration compared with intravenous administration. Taken together, the F-LbL film can selectively bind to colon tumors for localized delivery of drugs to treat colon cancer.

Aquasomes (AQ) are self-assembled nanostructures, made up of a spherical hydroxyapatite core and a carbohydrate layer on top, for delivering bioactive molecules like proteins, peptides, etc., which are adsorbed on the carbohydrate layer. This is the first report of its kind demonstrating AQ as an efficient dual drug delivery system, capable of releasing bioactive molecule and a hydrophobic drug together. The synthesized AQ before and after adsorption of the bioactive molecule are characterized using dynamic light scattering, scanning electron microscopy, X-ray diffraction, small-angle X-ray scattering, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and Raman spectroscopy. BSA (bovine serum albumin) protein is used as the model bioactive molecule for the in vitro dual release studies along with representative hydrophobic drugs Coumarin 153 (C153), Warfarin (WAR), and Ibuprofen (IBU). The release behaviors of the hydrophobic drugs are explained by studying their binding interactions with BSA. The binding interactions of the drugs with BSA are analyzed by carrying out fluorescence quenching experiment of BSA, site marking competition experiment, anisotropy, and E T (30) studies. Further, in vitro biocompatibility studies are performed for dually loaded AQ by using hemolysis assay. The hemolysis assay do not show any lysing of the red blood cells, suggesting the formulations to be clinically capable for administration.

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The aim of the study was to investigate the pharmacokinetic parameters of 5-fluorouracil (5FU) and moxifloxacin (MF) after oral administration using layer-by-layer assembled film in enteric coated capsule. The LbL film was prepared by sequential layering of chitosan and sodium alginate polyelectrolytes containing either 5FU or MF. The films were characterized for physical characteristics, drug loading and release behaviour. Pharmacokinetic studies were performed in the rat model for three different drug concentrations after oral administration and compared with intravenous administration. The results showed that the thickness of 10 bilayerd film was 147 ± 11.66 and 212.3 ± 7.19 µm after 5FU and MF loading, respectively. The amount of 5FU and MF loaded was found to be 1.93 ± 0.48 and 4.64 ± 0.33 mg/cm2, respectively. The DSC and PXRD results showed crystalline nature of 5FU and MF after entrapment in LbL film. The LbL film with backing layer provided directional release of 5FU and MF, where 63.81 ± 4.52% and 101.38 ± 5.08%, respectively was released in 24 h. 5FU showed non-linear pharmacokinetics compared with linear pharmacokinetics showed by MF after oral administration. There is a dose dependent increase in Cmax after oral administration of 5FU and MF LbL film. The Tmax was found to be 720 and 840 mins for 5FU and MF after oral administration. The mean residence time and AUC0-t at 45 mg/kg were 871.4 ± 6.45 min and 198.6 ± 5.03 x 103 min. ng/mL and 1267 ± 142.4 min and 1590 ± 55.60 103 min. ng/mL for 5FU and MF, respectively. Biodistribution studies showed significantly (p<0.01) greater disposition of 5FU within colon tissue after administration using oral LbL film. Taken together, colon targeted LbL film can be developed for oral administration of drugs for local and systemic applications.