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This study aims to develop a novel thermoresponsive system (TRS) of Niclosamide (Ncl) with improved localization, bioavailability, therapeutic efficacy and safety evaluation. Ncl has excellent therapeutic potential for many diseases including ulcerative colitis, yet associated with extremely poor aqueous solubility and bioavailability. Herein, we reported a TRS for colon specific delivery with mucoadhesive properties, improved dissolution and bioavailability. Ncl TRS was prepared by cold method and was optimized by using different concentrations of poloxamer 188 (P188), Tween® 80 (T80) and Ncl in a series of experiments. Physicochemical characterization of the prepared formulations were performed including, gelation temperature, gelation time, gel strength, mucoadhesive force and physical appearance. The optimized formulation was composed of [P188/P407/T80/Ncl/Water; 17/13/7/2/61, w/w] and showed optimum gelation temperature (30.5 ± 0.3 °C) and was quickly gelled inside the body (0.7 ± 0.5 min). Moreover, it was a clear, transparent liquid with a suitable gel strength (14150 ± 230 mPa s) and was mucoadhesive in nature. A significant effect on the physicochemical properties of the Ncl-TRS was observed by changing the concentration of the variables. The formulation was found stable for at least 6 months. Moreover, a meaningfully enhanced (7-fold) in vitrorelease and 6-fold improved bioavailability was projected by Ncl-TRS as compared to Ncl suspension. Furthermore, the Ncl-TRS was found to be in vivolocalized in the colon for at least 6 h, with no of toxicity after rectal administration. Additionally, the Ncl-TRS demonstrated a remarkable treatment potential of the ulcerative colitis in rat model with reduced signs of colon inflammation. It was concluded that the TRS could be a suitable carrier for pharmaceutical agents with improved bioavailability and therapeutic efficacy in ulcerative colitis.

The purpose of this study was to enhance the biopharmaceutical performance of Dexibuprofen (DXI) using transfersomal gel (DXI-TG) as drug delivery system. DXI loaded transfersomes (DXI-T) were prepared via thin film technique, characterized for particle size, polydispersity index, zeta potential, particle morphology and entrapment efficiency. The DXI-T was further incorporated into 2 % (w/v) chitosan gel to get the final dosage form DXI-TG, which was characterized for homogeneity, pH, spread-ability and rheological properties. In vitrorelease, ex vivopermeation and in vivostudies were also conducted along with stability study of the optimized formulation. DXI-T showed excellent vesicle properties including, size distribution (235.1 ± 4.66 nm), poly dispersity index (0.184 ± 0.001), zeta potential (−10.5 ± 0.23 mV) and entrapment efficiency (82.9 ± 1.07 %). TEM analysis exhibited spherical morphology and uniformly distributed nanoparticles, whereas FTIR showed no bond anomalies. DXI-TG showed suitable gel properties with a viscosity of 11310 ± 20 cP, pH 5.2 ± 0.3, good homogeneity, non-Newtonian flow behavior, good spread-ability (298 ± 7.63 %) and high drug content (97.01 ± 3.1 %). in vitrorelease studies demonstrated that DXI-TG has significantly controlled the release of DXI when compared with DXI-T, DXI-G and DXI-Suspension at pH 5.5 and 7.4. Similarly, ex vivopermeation analysis showed meaningfully increased permeation of DXI-T followed by DXI-TG when compared with test formulations. Like normal control group, skin irritation studies showed no erythema and edema in DXI-TG treated group. Additionally, DXI-TG demonstrated a significantly enhanced bioavailability (5-fold) when compared with DXI-Suspension and DXI-G. Furthermore, DXI-TG showed significantly enhanced therapeutic effect against acute arthritis model when compared with DXI-Suspension and DXI-G. Besides, no signs of evident toxicity on major body organs was observed in DXI-TG treated animal group. Also, the DXI-TG was found stable for a period of 6 months. It can be concluded that transfersomal gel may be a suitable carrier for DXI with enhanced bioavailability, improved therapeutic efficacy and no evident toxicity as exhibited in this study.

Regorafenib (RG), a multi-targeting kinase inhibitor, has recently been used in the colorectal cancer (CRC) treatment. However, its clinical effectiveness is severely constrained by its poor water solubility, extensive hepatic metabolism, low oral bioavailability, and serious side effects like Hand-foot skin reaction (HFSR), rashes, fatigue, stomatitis, diarrhea, dizziness and hypertension. Therefore, it is necessary to investigate alternative administration routes in order to increase RG efficacy. The aim of this study was to develop RG loaded liquid suppository with enhanced bioavailability and reduced toxicity. RG loaded liquid suppository was optimized using Design Experts® software, with various quantities of drug (RG), polymers [poloxamer 407 (P407), and poloxamer 188 (P188)], surfactant [Tween® 80, (T80)] and distilled water. Physicochemical characterization and in vitrostudy of RG release behavior from liquid suppository [RG/P188/P407/T80/distilled water: 1.25/15/11/10/62.75; %] were investigated followed by in vitrocell lines study on Caco-2 and HCT 116 cell lines. Additionally, pharmacokinetics, in vivosafety and in vivolocalization studies were carried out following rectal administration in Sprague-Dawley rats. Results showed that increased P407 and T80 concentrations significantly lowered the temperature and time required for gelation, while the strength and mucoadhesion of gel was meaningfully enhanced. However, RG concentration increased didn't show significant effect on all these parameters. RG loaded liquid suppository displayed a significantly improved in vitrorelease, augmented in vivolocalization, and enhanced bioavailability, when compared with the RG suspension. In vitrocell lines data demonstrated that unlike normal saline treated cell lines, the RG loaded liquid suppository and RG suspension has significantly reduced the cancer cell burden, which was also observed through their lower IC50values. Histopathology study confirmed the formulation's safety for rectal administration, whereas, RG suspension instigated severe damage to the rectal tissues. It can be concluded from the results that RG loaded liquid suppository has a great potential to target CRC with enhanced drug localization, improved bioavailability and no toxic effects at the application's site.