Sohail Akhter

Gold nanoparticles in theranostic oncology: current state-of-the-art

Introduction: In recent years, extensive multidisciplinary investigations have been carried out in the area of cancer nanotechnology. Gold nanoparticles (GNPs) have emerged as promising carrier for delivery of various pay-loads into their target. In view of their unique physicochemical and optical properties, GNPs have been exploited for multimodality imaging, tumor targeting, and as transporter of various therapeutics. Additionally, GNPs have been used as photothermal therapeutics against cancer. Areas covered: This review will focus on recent progress in the field of gold nanomaterials in cancer therapy and diagnosis. Moreover, concern about the toxicity of gold nanomaterials is addressed. Expert opinion: GNPs present versatile scaffolds for efficient delivery of cancer chemotherapeutics. Tuneable chemistry of the GNPs contributes to their ever increasing use in oncology research. The promises of a functional cancer therapy using GNPs have been extensively demonstrated, although the materials are still in their infancy stage and not surfaced to meet clinical standards.

Enhanced bioavailability of nano-sized chitosan–atorvastatin conjugate after oral administration to rats

A novel approach to improve the bioavailability and stability of atorvastatin (AT) was developed by constructing a nano-sized polymer-atorvastatin conjugate. Firstly, a novel chitosan-atorvastatin (CH-AT) conjugate was efficiently synthesized through amide coupling reaction. The formation of conjugate was confirmed by (1)H NMR and FT-IR spectrometry. Nano-sized conjugate with a mean size of 215.3±14.2 nm was prepared by the process of high pressure homogenization (HPH). Scanning electron microscopy (SEM) revealed that CH-AT nano-conjugate possess smooth surface whereas X-ray diffraction (XRD) spectra demonstrated amorphous nature of nano-conjugate. Further, CH-AT nano-conjugate showed solubility enhancement of nearly 4-fold and 100-fold compared to CH-AT conjugate and pure AT, respectively. In vitro drug release studies in simulated gastric fluid and simulated intestinal fluid suggested sustained release of AT from the conjugate. Additionally, the nano-conjugate significantly reduced the acidic degradation of AT. The plasma-concentration time profile of AT after oral administration of CH-AT nano-conjugate (2574±95.4 ng/mL) to rat exhibited nearly 5-fold increase in bioavailability compared with AT suspension (583±55.5 ng/mL). Finally, variable bioavailability, as observed for AT suspension was also reduced when AT was administered in form of CH-AT nano-conjugate. Taken together these data demonstrate that chitosan conjugate nano-prodrugs may be used as sustained polymeric prodrugs for enhancing bioavailability.

Nanomedicines as cancer therapeutics: current status.

As of 21st century, cancer is arguably the most complex and challenging disease known to mankind and an inevitable public health concern of this millennium. Nanotechnology, suitably amalgamated with cancer research, has ushered an era of highly personalized and safer medicines which can improve cancer diagnosis and therapy. A wide variety of nanomedicines are currently under investigation, including polymeric/non-polymeric nanoparticles, dendrimers, quantum dots, carbon nanotubes, lipid- and micelle-based nanoparticles. The bases of these nanomedicines in reducing toxicity associated with cancer therapy are their ability to carry a large payload and multivalent-ligand targeting. This imparts specificity for targeting the tissues as well as bypass resistance mechanisms. The major hurdles on these future medicines are potential toxicity of nanoparticles, which imposes the need of extensive regulatory evaluation before nanomedicines could be utilized as cancer therapeutics. This review highlights nanopharmaceuticals that have been investigated in oncology for various applications (diagnosis, therapeutic delivery and theranostics). It also discusses the effects of nano-sized materials on tissues/organ functions, the possibility of overcoming multi-drug resistance by using nanomedicines and their current clinical status.

Metallic nanoparticles: technology overview & drug delivery applications in oncology.

Importance of the field: The targeted delivery of therapeutic agents to tumour cells is a challenge because most of the chemotherapeutic agents distribute to the whole body, which results in general toxicity and poor acceptance by patients and sometimes discontinuation of the treatment. Metallic nanoparticles have been used for a huge number of applications in various areas of medical treatment. Metallic nanoparticles are emerging as new carrier and contrast agents in cancer treatment. These metallic nanoparticles have been used for imaging of tumour cells by means of active and passive targeting. Recent advances have opened the way to site-specific targeting and drug delivery by these nanoparticles. Areas covered in this review: This review summarizes the mechanisms of passive and active targeted drug delivery by metallic nanoparticles and their potential use in cancer theranostics. What the reader will gain: The reader will gain information on the development of tumour cells, advantages of modern methods of cancer treatment over the traditional method, targeted delivery of anticancer agents using nanoparticles, influence of nanotechnology on the quality and expectancy of life, and challenges, implications and future prospects of metallic nanoparticles as probes in cancer treatment. Take home message: The development of metallic nanoparticles is rapid and multidirectional, and the improved practical potential of metallic nanoparticle highlights their potency as new tools for future cancer therapeutics modalities.

Nanocarrier based formulation of Thymoquinone improves oral delivery: Stability assessment, in vitro and in vivo studies

This research aims to formulate and characterize solid lipid nanoparticles (SLNs) of Thymoquinone (THQ-SLNs) for the effective treatment of liver cirrhosis. Formulations were prepared using solvent injection method and optimized by the Box-Behnken experimental design to get the desired particle size having maximized entrapment efficiency as well as percentage release. Optimized THQ-SLNs (ST-1) with appropriate characteristics (particle size=166.1±10.96 nm; zeta potential=-11.34±3.54 mV; entrapment efficiency=71.60±3.85%; maximum % release=70.95±2.47%) were fabricated. DSC and XRD studies were carried out which collectively proved the reduced crystallinity and stability enhancing effect of the SLNs. Improved drug stability was further established by the subjection of the THQ-SLNs to accelerated stability studies (as per ICH guidelines) in contrast to the THQ-suspension. In vivo studies revealed a nearly 5 fold increase in the bioavailability of ST-1 (AUC(0→∞)=2998.91±260.503 μg/mL/h) as compared to THQ suspension (AUC(0→∞)=484.23±21.755 μg/mL/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (SGOT, SGPT and ALP) after oral administration of THQ-SLNs as compared to control and marketed (SILYBON(®)) formulations against paracetamol (PCM)-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections.

Classical to Current Approach for Treatment of Psoriasis: A Review

Psoriasis is a genetic predisposition with T-cell mediated autoimmune inflammatory skin disorder, characterized by cutaneous inflammation, increased epidermal proliferation, hyperkeratosis, angiogenesis, and abnormal keratinization that affects up to 2 - 3% of the population worldwide. Common therapies that are used for the treatment of psoriasis include topical, systemic, phototherapy, combination, herbal therapy and novel molecules. Topically used agents include Vit D, calcipotriol, corticosteroids, dithranol and retinoids etc. Systemically used agents include methotrexate and cyclosporine etc. Phototherapy includes UV-B, Psoralen plus ultraviolet therapy and excimer laser etc. These therapies have a number of potential problems, such as limited in efficacy, inconvenience, organ toxicity, carcinogenic and broadband immunosuppression. In natural treatment a variety of natural agents such as methanolic extracts of duzhong (Eucommia ulmoides Oliv.), yerba mate (Ilex paraguariensis,) linseed oil, fish oil, and Indigo naturalis etc., that modulates T cell and cytokine action at various steps along with the pathogenic sequence have been developed. But till now there is no more in vivo, dose and its efficacy data has been established. Current therapy includes biologicals, small molecules inhibitor and enzyme inhibitors etc, which serve as novel therapeutic options for psoriasis treatment. All these avoid the side effects of the prebiologically developed systemic agents including hepatotoxicity, nephrotoxicity, and bone marrow suppression. Currently, Denilukin diftitox, Efalizumab, Alefacept, Ustekinumab and Etanercept are approved by the FDA, and others molecules are at clinical stage. Patents issued by the US office are also included in current psoriasis treatment scenario. In the United States, biologicals are widely used for moderate-to-severe psoriasis. But because of the high cost of medication and their availability in injection form, it remains to be seen how widely these agents will be utilized worldwide. Still, developing countries prefer conventional drugs.

Investigation of Nanoemulsion System for Transdermal Delivery of Domperidone: Ex-vivo and in vivo Studies

The aim of the present study was to investigate the nanoemulsion system for enhanced percutaneous penetration of domperi- done. Pseudoternary phase diagrams were constructed in order to optimize the surfactant, cosurfactant and surfactant: cosurfactant weight ratios (Smix). Nine nanoemulsion formulations were selected, characterized and their ex-vivo permeation studies using rat skin were per- formed. The nanoemulsion formulations had small droplet size (<90 nm), uniform size distribution (PI, < 0.2) and low viscosity (<160 mP). The results demonstrated that the droplet size and viscosity of nanoemulsion decreased following decrease in the concentration of polysorbate 20, whereas transdermal flux was increased. The optimized formulation NE-B1, which contained oleic acid (4 % w/w), polysorbate 20 (10 % w/w), diethylene glycol monoethyl ether (20 % w/w) and water (64 % w/w) showed significant increase (P < 0.01) in the transdermal flux (169.32 ± 8.33 � g.h -1 cm -2 ). The in vivo studies revealed a 3.5 fold increase in relative bioavailability through transdermal application of NE-B1 formulation compared to oral drug suspension. Moreover, the effective drug plasma concentration was maintained for 16 hour after the transdermal application indicated that the developed nanoemulsion systems could be a promising carrier for the transdermal delivery of domperidone for prolonged period. Microemulsions are quaternary systems composed of an oil phase, a water phase, surfactant frequently in combination with cosurfactant (1-3). These spontaneously formed systems possess specific physicochemical properties such as transparency, optical isotropy, low viscosity and thermodynamic stability. In stable mi- croemulsion, droplet diameter is usually within the range of 10-100 nm (100-1000 A°), and therefore these systems are also termed as nanoemulsions (NE) (4). Due to their unique physicochemical properties, NE offer advantages over traditional topical and trans- dermal drug delivery formulations. Many studies have shown that NE formulations possess improved transdermal and dermal delivery properties both in vitro (5-17), as well as in vivo (18-22). The high solubilizing capacity of NE enables them to increase the solubility of poorly water-soluble drugs. Both, increase in solute concentra- tion and the tendency of the drug to favor partitioning into the stra- tum corneum make NE a useful vehicle to enhance transdermal drug permeability (23). As demonstrated by a recent publication (18), the transdermal permeation rate of a lipophilic drug significantly increased from NE as compared to macroemulsions. In macroemulsions the free mobil- ity of the active material between the internal (disperse) phase to the external (continuous) phase within the structure of the formu- lated system is limited due to the strong interactions between the surfactants that form tight interfacial film. In NE, the co-surfactant lowers the interfacial tension of the surfactant film, resulting in a more flexible and dynamic layer (3,14). The drug in this energy- rich system can diffuse across the flexible interfacial surfactant film, a thermodynamic process that increases partitioning and diffu- sion into the stratum corneum. This article is intended to demonstrate the feasibility of new o/w NE system for transdermal delivery of domperidone. Domperi- done is a dopamine (D2 receptor) antagonist with predominant peripheral activity. It is clinically effective in conditions such as diabetic gastroparesis, chronic dyspepsia, pediatric vomiting, cancer chemotherapy induced nausea and emesis (24). Owing to its high portion of hepatic first pass metabolism (~85 %) (25), its low mo- lecular weight (426 Da), its moderate lipophilicity (Log P, 3.9) as

Microscopic and spectroscopic evaluation of novel PLGA–chitosan Nanoplexes as an ocular delivery system

The interaction of PLGA-chitosan Nanoplexes with ocular mucosa was investigated ex vivo and in vivo to assess their potential as ocular delivery system. Fluorescent Rhodamine Nanoplexes (Rd-Nanoplexes) were prepared by ionotropic gelation method. The size and morphology of Nanoplexes was investigated by TEM, SEM and PCS. The corneal retention, uptake and penetration of Nanoplexes were analyzed by spectrofluorimetry and confocal microscopy. Corneas from Rd-Nanoplexes-treated rabbits were evaluated for the in vivo uptake and ocular tolerance. The Nanoplexes prepared were round with a mean diameter of 115.6±17nm and the encapsulation efficiency of Rd was 59.4±2.5%. Data from ex vivo and in vivo studies showed that the amounts of Rd in the cornea were significantly higher for Nanoplexes than for a control Rd solution, these amounts being fairly constant for up to 24h. Confocal microscopy of the corneas revealed paracellular and transcellular uptake of the Nanoplexes. The uptake mechanism postulated was adsorptive-mediated endocytosis and opening of the tight junctions between epithelial cells. No alteration was microscopically observed after ocular surface exposure to Nanoplexes. Taken together, these data demonstrate that Nanoplexes are potentially useful as ocular drug carriers.

Nanometric gold in cancer nanotechnology: current status and future prospect

This review elaborate on modified gold nanoparticulate concept in oncology, provides an overview of the use of gold nanoparticles in cancer treatment and discusses their potential applications and clinical benefits.

Advancement in multifunctional nanoparticles for the effective treatment of cancer

Introduction: Nanotechnology has gained wider importance for the treatment of various diseases, including cancer. Multifunctional or theranostic agents are emerging as promising therapeutic paradigms, which provide attractive vehicles for both image and therapeutic agents. Nanosystems are capable of diagnosis, specific targeted drug therapy and monitoring therapeutic response. Due to their well-developed surface nature, nanomolecules are easy to anchor with multifunctional groups. Areas covered: The present review aims to give an extensive account on the progress of multifunctional nanoparticles throughout the blooming research with regards to their clinical application in cancer. This paper discusses graphene, a newly developed multifunctional vehicle in nanotechnology. Furthermore, it focuses on the development of tumor cells, the advantages of novel multifunctional nanoparticles over traditional methods and the use of nanoparticles in cancer therapy. In addition, patents issued by the US office are also included. Expert opinion: Despite numerous advantages, multifunctional nanoparticles are still at an infancy stage. Many great achievements have been attained in this field to date, but many challenges still remain. A problem that limits the use of multifunctional nanoparticles is toxicity. If this toxicity can be overcome then the advancement in nanocomposite material science will be well on the way to a prospective treatment of cancer.