Mucoadhesive gastroretentive microparticulate system for programmed delivery of famotidine and clarithromycin.

AIM: The present research was aimed to develop thiolated polyacrylic acid (TPA) based microspheres (MSPs) containing famotidine (FX) and clarithromycin (CLX). METHODS: TPA was synthesised from polyacrylic acid and l-cysteine in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC). The prepared TPA was characterised using FT-IR (Fourier transform-infra red), 1H-NMR (proton nuclear magnetic resonance) spectroscopy, P-XRD (powder X ray diffraction) method, and zeta potential. The analytical tools have supported the formation of TPA. The thiolated microspheres were prepared by emulsion solvent evaporation method using 0.75% w/v polymer concentration and stirring at 400 rpm for 8 hr. RESULTS: The average particle size and zeta potential of optimised formulation was found to be 25.2 ± 1.87 µm and -26.68 mV, respectively. The entrapment efficiency of the optimised formulation was obtained 67.20% for FX and 70.20% for CLX. The developed microspheres were swelled only in 4 h from 0.5 to 0.9. The in vitro mucoadhesive study and in vitro drug release studies demonstrated that microspheres showed mucoadhesive property. In in vitro drug release studies, the release of FX and CLX were observed to be 58.68% and 60.48%, respectively from microspheres in 8 h. The thiolated microspheres showed higher adhesion time (7.0 ± 0.8 h) in comparison to the plain microspheres (2.6 ± 0.4 h). CONCLUSION: The prepared TPA based mucoadhesive microspheres can be utilised as carriers for the treatment of peptic ulcer caused by Helicobacter pylori which will offer enhanced residence time for the rational drug combination in the gastric region.

Folate Conjugated Double Liposomes Bearing Prednisolone and Methotrexate for Targeting Rheumatoid Arthritis.

PURPOSE: This investigation was aimed to explore the targeting potential of folate conjugated double liposomes (fDLs) bearing combination of synergistic drugs (Prednisolone and Methotrexate) for effective management of the rheumatoid arthritis (RA). METHODS: To overcome the drawbacks of monotherapy, a combination of prednisolone (PRD) (an anti-inflammatory agent) and methotrexate (MTX) (a disease modifying anti-rheumatoid agent, DMARDs) was chosen for dual targeting approach. fDLs were prepared in two steps i.e. development of inner liposomes (ILs) using thin film casting method followed by encapsulation of ILs within folate conjugated outer liposomes (double liposomes; fDLs). Developed liposomes were characterized for various physicochemical parameters and in vivo performance. RESULTS: fDLs were prepared using FA-PEG-4000-NH-DSPE conjugate. These double liposomes were having 429.3 ± 3.6 nm in size with 0.109 PDI, 8.01 ± 0.3 mV zeta potential (ζ) and 66.7 ± 3.9% and 45.3 ± 1.7% entrapments of PRD and MTX, respectively. After 24 h, the concentrations of PRD in blood were observed to be 8.66 ± 3.11 (ILs) and 15.13 ± 0.81% (DLs) while concentration of MTX were found to be 10.89 ± 0.69 and 2.34 ± 3.15% when given as ILs and fDLs, respectively. The concentration of both drugs in inflamed joint was observed to be higher than that in the non-inflamed joints. CONCLUSIONS: The folate conjugated double liposomes possess superior targeting efficiency than conjugated and unconjugated single liposomes.

Basics to advances in nanotherapy of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer existing across the globe. It begins with the formation of polyps leading to the development of metastasis, especially in advanced stage patients, who necessitate intensive chemotherapy that usually results in a poor response and high morbidity owing to multidrug resistance and severe untoward effects to the non-cancerous cells. Advancements in the targeted drug delivery permit the targeting of tumor cells without affecting the non-tumor cells. Various nanocarriers such as liposomes, polymeric nanoparticles, carbon nanotubes, micelles, and nanogels, etc. are being developed and explored for effective delivery of cytotoxic drugs to the target site thereby enhancing the drug distribution and bioavailability, simultaneously subduing the side effects. Moreover, immunotherapy for CRC is being explored for last few decades. Few clinical trials have even potentially benefited patients suffering from CRC, still immunotherapy persists merely an experimental alternative. Assessment of the ongoing and completed trials is to be warranted for effective treatment of CRC. Scientists are paying efforts to develop novel carrier systems that may enhance the targeting potential of low therapeutic index chemo- and immune-therapeutics. Several preclinical studies have revealed the superior efficacy of nanotherapy in CRC as compared to conventional approaches. Clinical trials are being recruited to ascertain the safety and efficacy of CRC therapies. The present review discourses in a nutshell the molecular interventions including the genetics, signaling pathways involved in CRC, and advances in various strategies explored for the treatment of CRC with a special emphasis on nanocarriers based drug targeting.