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.

Combination Cancer Therapy Using Multifunctional Liposomes.

Chemotherapy of cancer is still considered a complex phenomenon given that single chemotherapeutic agents cannot be administered for a long period of time because of the development of drug resistance and severe side effects. Nanodrug delivery systems (NDDSs) such as nanoparticles and liposomes are being investigated to enhance the safety and efficacy of anticancer agents. NDDS-based delivery of a single agent is not found to be effective in long-term anticancer therapy. Codelivery of more than one anticancer agent using liposomes shows great potential since it exhibits simultaneous synergistic therapeutic manifestations at the tumor site and enhances therapeutic efficacy in terms of the low-dose requirement of each agent and diminished side effects. Liposomes are lipid vesicles arranged in concentric bilayers with an aqueous core; they are versatile nanocarriers that accommodate the diverse nature of anticancer drugs (both hydrophobic and hydrophilic) at the same time. They offer a number of advantages for combinatorial drug delivery in terms of increased blood circulation, selective accumulation at tumor tissues, and stimuli responsiveness. Various combination of drugs such as paclitaxel (PTX) and topotecan, sunitinib and irinotecan, and combretastin A-4 and doxorubicin have been reported for cancer chemotherapy using liposomes. This review focuses on recent scenarios of combinatorial drug delivery using liposomes for better chemotherapeutic outcomes. This assemblage can be of great importance to researchers looking for advances in novel drug delivery approaches for better cancer treatment.

Glutamate-conjugated liposomes of dopamine hydrochloride for effective management of parkinsonism's.

The blood-brain barrier restricts the brain uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, amino acid-coupled liposomes bearing dopamine HCl were prepared to deliver the drug to the brain utilizing receptor-mediated transcytosis. Uncoupled liposomes were prepared by cast film method using phosphatidylcholine and cholesterol, whereas coupled liposomes were prepared using phosphatidylcholine, cholesterol, and glutamate stearylamine conjugate in the film. These liposomes were characterized for entrapment efficiency, vesicle size, shape, in vitro drug release, and in vivo studies. The in vitro drug release was analysed by using dialysis membrane. The vesicle size was found to increase upon coupling of liposomes, whereas percent entrapment efficiency was reduced from 38.89 +/- 1.94% to 34.15 +/- 1.70% after coupling of liposomes. The in vitro percent cumulative drug release studies exhibited 51.6% drug release for uncoupled liposome and 37.9% for coupled liposome at the end of 24 h. These selected formulations were subjected for in vivo performance, which was assessed by periodic measurement of drug (chlorpromazine)-induced catatonia in albino rats (Wistar strain) and fluorescence microscopy studies of the rat brain. The results were compared with plain dopamine HCl solution. Studies revealed that dopamine HCl can be effectively delivered to brain via glutamate-coupled liposomes, and results clearly indicated the superiority of the coupled liposomal formulation over the uncoupled formulation.

Topotecan Liposomes: A Visit from a Molecular to a Therapeutic Platform.

Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases. This review discusses these problems and the means to overcome them, including modification of TLs using zwitterionic poly(carboxybetaine), prolongation in dosing interval (long-term therapy), and modified liposomal encapsulation techniques including active loading methods. We also explore engineered TLs (surface and integral modifications) such as PEGylated TLs, ligand-anchored TLs, and stimuli-sensitive TLs. Further, potential applications, manifestations at the molecular level, patents granted, and preclinical and clinical outlook for TLs are discussed.

Microsponges: A Pioneering Tool for Biomedical Applications.

Microparticulate drug delivery systems have been explored across the globe due to their various advantages. In 1987, Won developed microsponge systems (Micsys), also known as solid-phase porous microspheres, having numerous interconnected voids, which serve as non-collapsible residence for bioactive compounds. A Micsys particle ranges from 5 to 300 µm in size and shows a wide range of entrapment efficiency with desired release rates. This topical drug delivery system bestows a controlled release of bioactive compounds into the skin with reduced systemic side effects. Currently, the application fields of this promising system include oral, ocular, pulmonary, and parenteral delivery of bioactive compounds. In the present review, we summarize the updated biomedical application potential of Micsys as an effective drug-delivery vector, including an in-depth explanation of the drug-release kinetic models and drug-release mechanisms. We also discuss different techniques used to prepare a Micsys, along with their advantages and disadvantages. Moreover, in this review, we report a plethora of Micsys details, such as drug candidates and polymers, exploited in this field, along with marketed formulations, characterization methods, clinical perspectives, and patents received. This assembly of detailed literature summaries will contribute to future advances in the development of porous carriers.

Liposomes a vesicular nanocarrier: potential advancements in cancer chemotherapy.

The indispensable obligation behind the successful therapy of a disease is to deliver the effective drug/bioactive concentration with sustained release manner at the diseased organs without any exposure to the healthy tissues. Novel drug-delivery systems increase the concentration and persistence of drug at the vicinity of the target site and thereby minimize the undesired side effects of the drug to the normal tissues of body. With advances in nanotechnology, several new drug delivery approaches have become available that may fulfil the requirement of safe and effective drug therapy. Among these techniques, vesicular drug-delivery systems, particularly liposomes, are under rigorous research for their applicability to deliver FDA-approved and newer drugs. Liposomes have been widely investigated as one of the most widely used nanocarriers in cancer therapy and have shown their potential in spatial and temporal release of bioactive agents for the effective treatment of various life-threatening diseases, including cancer. Various targeted and triggered-release approaches of bioactive substances using liposomes further improve the applicability of liposomes in cancer therapeutics. Thus, keeping these points in view, the present review has been focussed on application of liposomes for development of liposome technology and its novel applications for effective cancer therapy.