Gold liposomes for brain-targeted drug delivery: Formulation and brain distribution kinetics.

This work was aimed to formulate transferrin (Tf) receptor targeted gold based theranostic liposomes which contain both docetaxel (DCX) and glutathione reduced gold nanoparticles (AuGSH) for brain-targeted drug delivery and imaging. AuGSH was prepared by reducing chloroauric acid salt using glutathione. The co-loading of DCX and AuGSH into liposomes was achieved by the solvent injection technique, and Tf was post-conjugated on the surface of the liposomes using carboxylated Vit-E TPGS (TPGS-COOH) as a linker. The liposomes were characterized for various parameters such as size, shape, surface charge, and drug release. The Tf receptor targeted gold liposomes were evaluated for the cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based colorimetric assay and in-vitro qualitative cellular uptake studies using confocal microscopy. The in-vivo site specific delivery of DCX was analyzed by the brain distribution study of DCX in comparison with marketed formulation (Docel™). A sustained drug release of about 70% was observed from liposomes in the span of 72 h. The in-vivo results demonstrated that targeted gold liposomes were able to deliver DCX into the brain by 3.70, 2.74 and 4.08-folds higher than Docel™ after 30, 120 and 240 min of the treatment, respectively. Besides, the results of these studies have suggested the feasibility of Tf decorated AuGSH and DCX co-loaded liposomes as a promising platform for targeted nano-theranostics.

Formulation and in vitro evaluation of upconversion nanoparticle-loaded liposomes for brain cancer.

Aim: This work focused on the development of transferrin-conjugated theranostic liposomes consisting of docetaxel (DXL) and upconversion nanoparticles for the diagnosis and treatment of gliomas. Materials & methods: Upconversion nanoparticles and docetaxel-loaded theranostic liposomes were prepared by a solvent injection method. Formulations were analyzed for physicochemical properties, encapsulation efficiency, drug release, elemental analysis, cytotoxicity and fluorescence. Results: The particle size was around 200 nm with spherical morphology and an encapsulation efficiency of up to 75.93%, was achieved for liposomes with an in vitro drug release of 71.10%. The IC50 values demonstrated enhanced cytotoxicity on C6 glioma cells with targeted liposomes in comparison with nontargeted liposomes. Conclusion: Prepared theranostic liposomes may be promising for clinical validation after an in vitro and in vivo evaluation on cell lines and animals, respectively.

Mannose receptor targeted bioadhesive chitosan nanoparticles of clofazimine for effective therapy of tuberculosis.

Drug-resistant tuberculosis (TB) is one of the most lethal diseases, and it is imperative to exploit an advanced drug formulation for its effective treatment. This work aims to develop a mannose receptor-targeted bioadhesive chitosan nanoparticles for effective drug-resistant tuberculosis treatment. The clofazimine loaded chitosan nanoparticles were formulated; their size, charge, polydispersity (PDI), surface morphology, entrapment efficiency (EE) and in-vitro release pattern were established. Also, cellular uptake study on C2C12 cell lines and anti-mycobacterial activity against H37Rv (a standard strain of Mycobacterium tuberculosis) were evaluated. The particle sizes of formulated chitosan nanoparticles were in the range of 132-184 nm and EE was also found to be between 73 and 95%. The functionalization of bioadhesive chitosan nanoparticles with mannose was confirmed by infrared spectroscopy (FTIR). The uptake studies on the C2C12 cell lines showed that mannosylated nanoparticles were more efficiently internalized when compared to non-targeted nanoparticles. Further, luciferase reporter phage (LRP) assay against H37Rv strain showed that clofazimine nanoparticles were found to be 49.5 times superior in terms of inhibition and anti-mycobacterial activity than free clofazimine. This excellent activity might be attributed to enhanced drug delivery with a promising bioadhesion property of chitosan-based nanoparticles.

Nanotheranostics: Emerging Strategies for Early Diagnosis and Therapy of Brain Cancer.

Nanotheranostics have demonstrated the development of advanced platforms that can diagnose brain cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In brain nanotheranostics, therapeutic as well as diagnostic entities are loaded in a single nanoplatform, which can be further developed as a clinical formulation for targeting various modes of brain cancer. In the present review, we concerned about theranostic nanosystems established till now in the research field. These include gold nanoparticles, carbon nanotubes, magnetic nanoparticles, mesoporous silica nanoparticles, quantum dots, polymeric nanoparticles, upconversion nanoparticles, polymeric micelles, solid lipid nanoparticles and dendrimers for the advanced detection and treatment of brain cancer with advanced features. Also, we included the role of three-dimensional models of the BBB and cancer stem cell concept for the advanced characterization of nanotheranostic systems for the unification of diagnosis and treatment of brain cancer. In future, brain nanotheranostics will be able to provide personalized treatment which can make brain cancer even remediable or at least treatable at the primary stages.