Madaswamy S Muthu

Nanotheranostics ˗ Application and Further Development of Nanomedicine Strategies for Advanced Theranostics

Nanotheranostics is to apply and further develop nanomedicine strategies for advanced theranostics. This review summarizes the various nanocarriers developed so far in the literature for nanotheranostics, which include polymer conjugations, dendrimers, micelles, liposomes, metal and inorganic nanoparticles, carbon nanotubes, and nanoparticles of biodegradable polymers for sustained, controlled and targeted co-delivery of diagnostic and therapeutic agents for better theranostic effects with fewer side effects. The theranostic nanomedicine can achieve systemic circulation, evade host defenses and deliver the drug and diagnostic agents at the targeted site to diagnose and treat the disease at cellular and molecular level. The therapeutic and diagnostic agents are formulated in nanomedicine as a single theranostic platform, which can then be further conjugated to biological ligand for targeting. Nanotheranostics can also promote stimuli-responsive release, synergetic and combinatory therapy, siRNA co-delivery, multimodality therapies, oral delivery, delivery across the blood-brain barrier as well as escape from intracellular autophagy. The fruition of nanotheranostics will be able to provide personalized therapy with bright prognosis, which makes even the fatal diseases curable or at least treatable at the earliest stage.

Targeted nanomedicines: effective treatment modalities for cancer, AIDS and brain disorders

Novel technology in the nanomedicine field is expected to develop innovative products as targeted drug-delivery approaches. Targeted drug delivery of various drugs for the treatment of cancer, AIDS and brain disorders is the primary research area in which nanomedicines have a major role and need. This review is concerned with emerging targeted nanomedicines (polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles, dendrimers, liposomes, gold nanoparticles and magnetic nanoparticles) and multifunctional carriers capable of combining targeted drug delivery and imaging (polymeric micelles, dendrimers and magnetic nanoparticles) in the field of pharmaceutical applications. The significant toxicity issues associated with these nanomedicines are also explored here.

Theranostic liposomes of TPGS coating for targeted co-delivery of docetaxel and quantum dots

The aim of this work was to develop a new type of D-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) coated multi-functional (theranostic) liposomes, which contain both docetaxel and quantum dots (QDs) for cancer imaging and therapy. Non-targeting and folate receptor targeting TPGS coated theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential, surface chemistry and drug encapsulation efficiency. MCF-7 breast cancer cells of folate receptor overexpression were employed as an in vitro model to assess cellular uptake and cytotoxicity of the drug and QDs loaded liposomes. The mean particle size of the non-targeting and the targeting liposomes was found to be 202 and 210 nm, respectively. High resolution field emission transmission electron microscopy (FETEM) confirmed the presence of quantum dots in the peripheral hydrophobic membranes of the liposomes. The qualitative internalization of multi-functional liposomes by MCF-7 cells was visualized by confocal laser scanning microscopy (CLSM). The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 9.54 ± 0.76, 1.56 ± 0.19 and 0.23 ± 0.05 μg/ml for the commercial Taxotere(®), non-targeting and targeting liposomes, respectively after 24 h culture with MCF-7 cells. The targeting multi-functional liposomes showed greater efficacy than the non-targeting liposomes and thus great potential to improve the cancer imaging and therapy.

Vitamin E TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cells.

The aim of this work was to develop a drug delivery system of liposomes, which are coated with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), a PEGylated vitamin E, with docetaxel as a model drug for enhanced treatment of brain tumour in comparison with the nude liposomes as well as with the so-called stealth liposomes, i.e. those coated with polyethylene glycol (PEG), which have been intensive investigated in the literature. Docetaxel or coumarin-6 loaded liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential and drug encapsulation efficiency. C6 glioma cells were employed as an in vitro model to access cellular uptake and cytotoxicity of the drug or coumarin-6 loaded liposomes. The particle size of the PEG or TPGS coated liposomes was ranged between 126 and 191nm. High-resolution field-emission transmission electron microscopy (FETEM) confirmed the coating of TPGS on the liposomes. The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 37.04±1.05, 31.04±0.75, 7.70±0.22, and 5.93±0.57μg/ml for the commercial Taxotere(®), the nude, PEG coated and TPGS coated liposomes, respectively after 24h culture with C6 glioma cells. The TPGS coated liposomes showed great advantages in vitro than the PEG coated liposomes.

PLGA nanoparticle formulations of risperidone: preparation and neuropharmacological evaluation.

UNLABELLED The aim of this work was to develop extended-release poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles of risperidone and thermal-responsive in situ gel containing risperidone nanoparticles for parenteral (subcutaneous) delivery and to reduce the dose-dependent extrapyramidal side effects of risperidone. PLGA nanoparticles of risperidone were designed by nanoprecipitation method using polymeric stabilizer (Poloxamer 407). The prepared nanoparticles were characterized for particle size by photon correlation spectroscopy and atomic force microscopy. Poloxamer 407-based in situ gel containing PLGA nanoparticles of risperidone was prepared by modified cold method to control the initial rapid release from the nanoparticles. The in vivo efficacy (antipsychotic effect) of prepared formulations (nanoparticles and in situ gel containing nanoparticles) was studied by administering them subcutaneously to mice. Extrapyramidal side effects of the formulations were also studied. The particle size of the prepared nanoparticles ranged between 85 and 219 nm. About 89% to 95% drug encapsulation efficiency was achieved when risperidone was loaded at 1.7% to 8.3% by weight of the polymer. During in vivo studies prepared risperidone formulations showed an antipsychotic effect that was significantly prolonged over that of risperidone solution for up to 72 hours with fewer extrapyramidal side effects. The prolonged effect of risperidone was obtained from the risperidone formulations administered subcutaneously, and this may improve the treatment of psychotic disorders by dose reduction. FROM THE CLINICAL EDITOR The development of extended-release poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles of risperidone is reported in this paper, along with the development of thermal-responsive in situ gel containing risperidone nanoparticles for parenteral (subcutaneous) delivery and to reduce the dose-dependent extrapyramidal side effects. In vivo studies showed a significantly prolonged antipsychotic effect with fewer extrapyramidal side effects.

Nanopharmacology of liposomes developed for cancer therapy

the necessary bending energy [5]. Liposomes are a promising dosage form/drug delivery system owing to their size, hydrophobic and hydrophilic character, biocompatibility, biodegradability, low toxicity and immunogenicity [6,7]. Indeed, liposome products were the first nanopharmaceuticals approved by the US FDA and are listed in the database of dosage forms with a FDA code of 852 [101]. Stealth liposomes are an emerging novel development in the technology to enhance their half-life in the bloodstream. Generally, the surfaces of these liposomes are modified with the attachment of polyethylene glycol (PEG) groups to the liposomal bilayer to avoid the opsonization process [8].

Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success

Liposomes are one of the effective drug delivery systems that are developed based on the nanotechnology concept. Liposomal formulation is the first nanomedicine approved by the US FDA for clinical application. Recently, the marketed liposomes and stealth liposomes have made impact for cancer therapy. In addition, a few receptor-targeted liposome products have been in different phases of clinical trials, which are yet to be marketed. In the present editorial, the advantages of vitamin E TPGS-coated liposomes over the currently available PEG-coated liposomes will be described and their great potentials for nanotheranostics for cancer imaging and therapy will be covered.

Stimulus-responsive targeted nanomicelles for effective cancer therapy

Emerging nanotechnology has already developed various innovative nanomedicines. Nanomicelles, self-assemblies of block copolymers, are promising nanomedicines for targeted drug delivery and imaging. Stimulus-responsive targeted nanomicelles are designed to release drugs based on stimuli such as pH, temperature, redox potential, magnetism and ultrasound. This article will focus on recent advancements in the design of stimulus-responsive targeted nanomicelles loaded with anticancer drugs to fulfill the challenges associated with cancer cells (e.g., multidrug resistance) for the effective treatment of cancer. The significant toxicity issues and a possible future perspective associated with nanomicelles are also discussed here.

Studies on biodegradable polymeric nanoparticles of risperidone: in vitro and in vivo evaluation.

AIM The aim of this work was to develop extended-release risperidone nanoparticles for parenteral delivery (intravenous) and to reduce the dose-dependent extrapyramidal side effects of risperidone. METHODS Polymeric nanoparticles containing risperidone made of poly (epsilon-caprolactone) were designed by the nanoprecipitation method using polymeric stabilizers (poloxamers). The in vivo efficacy of prepared formulations and the risperidone solution was studied by administering them intravenously to apomorphine-treated mice. Extrapyramidal side effects of the risperidone and its formulations were also studied. RESULTS The particle size of the prepared nanoparticles ranged between 99 and 304 nm. Approximately 78-85% drug-encapsulation efficiency was achieved when risperidone was loaded at 1.7-4.1% by weight of the polymer. During in vivo studies, prepared risperidone-containing formulations showed a significant prolonged antipsychotic effect than that of risperidone solution, also having less extrapyramidal side effects. CONCLUSION The prolonged effect of risperidone was obtained from the nanoparticles of risperidone administered by the intravenous route and this may improve the treatment of psychotic disorders by dose reduction.

Development of docetaxel-loaded vitamin E TPGS micelles: formulation optimization, effects on brain cancer cells and biodistribution in rats

AIM This work aimed to develop docetaxel-loaded D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for brain cancer chemotherapy by taking advantage of polyethylene glycol for its long half-life in circulation and vitamin E for its high cellular uptake. MATERIAL & METHODS TPGS micelles containing docetaxel or coumarin-6 were prepared by the solvent casting method and the direct dissolution method at high, moderate and low drug-loading levels. RESULTS & DISCUSSION The particle size of the docetaxel-loaded TPGS micelles ranged between 12 and 14 nm. Docetaxel formulated in the TPGS micelles of high, moderate and low drug-loading levels achieved lower IC(50) values compared with Taxotere after 24-h incubation with C6 glioma brain cancer cells. The TPGS has much lower critical micelle concentration than most phospholipids in micellar formulation, which can be an efficient drug carrier across the blood brain-barrier with high drug encapsulation efficiency, cell uptake, cytotoxicity and desired biodistribution of the formulated drug.