Encapsulation of Alpinia leaf essential oil in nanophytosome-embedded gel as novel strategy to treat periodontal infections: evaluation of antimicrobial effectiveness, pharmacokinetic, in vitro-ex vivo correlation and in silico studies.

AIM: The work reports a novel nanophytosomal gel encapsulating Alpinia galanga (L.) Willd leaf essential oil to treat periodontal infections. METHODS: Alpinia oil-loaded nanophytosomes (ANPs) were formulated by lipid layer hydration technique and were evaluated by FESEM, cryo-TEM, loading efficiency, zeta potential, particle size, release profile etc. Selected ANPs-loaded gel (ANPsG) was evaluated by both in vitro and in vivo methods. RESULTS: Selected ANPs were spherical, unilamellar, 49.32 ± 2.1 nm size, 0.45 PDI, -46.7 ± 0.8 mV zeta potential, 9.8 ± 0.5% (w/w) loading, 86.4 ± 3.02% (w/w) loading efficiency with sustained release profile. ANPsG showed good spreadability (6.8 ± 0.3 gm.cm/sec), extrudability (79.33 ± 1.5%), viscosity (36522 ± 0.82 cps), mucoadhesive strength (44.56 ± 3.5 gf) with sustained ex vivo release tendency. Satisfied ZOI and MIC was observed for ANPsG against periodontal bacteria vs. standard/control. ANPsG efficiently treated infection in ligature induced periodontitis model. Key pharmacokinetic parameters like AUC, MRT, Vd were enhanced for ANPsG. CONCLUSION: ANPsG may be investigated for futuristic clinical studies.

Green synthesis of silver nanoparticles using Eupatorium adenophorum leaf extract: characterizations, antioxidant, antibacterial and photocatalytic activities.

The green synthesis of metallic nanoparticles has tremendous impacts in various fields as found in recent years due to their low cost, easy and environmentally friendly synthesis. In this article, we report a simple and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using an aqueous Eupatorium adenophorum (E. adenophorum) leaf extract as a bioreductant. Interestingly, Fourier transform infrared (FTIR) spectroscopy analysis established that the E. adenophorum extract not only served as a bioreductant but also acted as a capping agent to stabilize the nanoparticles by functionalizing the surfaces. Various characterization techniques were adopted, such as X-ray powder diffraction (XRD), FTIR, ultraviolet-visible absorption (UV-Vis) spectroscopy, dynamic light scattering, scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDX) to analyze the biosynthesized AgNPs. Biosynthesized nanoparticles were also explored for antioxidant, antibacterial and photocatalytic activities. The AgNPs showed improved free radical scavenging activity (IC50 48.96 ± 0.84 µg/mL) and bacterial inhibitory effects against both gram-positive (Staphylococcus aureus; 64.5 µg/mL) and gram-negative (Escherichia coli; 82.5 µg/mL) bacteria. Photocatalytic investigation showed AgNPs were effective at degrading rhodamine dye (78.69% in 90 min) when exposed to sunlight. These findings collectively suggest that E. adenophorum AgNPs were successfully prepared without the involvement of any hazardous chemical and it may be an effective antibacterial, antioxidant and promising agent for the removal of hazardous dye from waste water produced by industrial dyeing processes.

Assessment of superiority of HSP70-targeting aptamer-functionalized drug-nanocarrier over non-targeted commercially available counterpart in HCC therapy: in vitro and in vivo investigations and molecular modeling.

AIMS: This research aims to compare the therapeutic potential of target-specific phosphorothioate backbone-modified aptamer L5 (TLS9a)-functionalized paclitaxel (PTX)-loaded nanocarrier (PTX-NPL5) that we formulated with that of non-targeted commercial formulation, protein albumin-bound nanoparticles of PTX, Abraxane® (CF) against hepatocellular carcinoma (HCC) through a myriad of preclinical investigations. MAIN METHODS: A variety of in vitro and in vivo assays have been executed to compare the therapeutic effects of the formulations under investigation, including the investigation of the degree of apoptosis induction and its mechanism, cell cycle analysis, the level of ROS production, and redox status, the morphological and histological characteristics of malignant livers, and in vivo imaging. The formulations were also compared concerning pharmacokinetic behaviors. Finally, in silico molecular docking has been performed to predict the possible interactions between aptamer and target(s). KEY FINDINGS: PTX-NPL5 exhibited therapeutic superiority over CF in terms of inducing apoptosis, cell cycle arrest, endorsing oxidative stress to neoplastic cells, and reducing hepatic cancerous lesions. Unlike CF, PTX-NPL5 did not exhibit any significant toxicity in healthy hepatocytes, proving enough impetus regarding the distinctive superiority of PTX-NPL5 over CF. The pharmacokinetic analysis further supported superior penetration and retention of PTX-NPL5 in neoplastic hepatocytes compared to CF. A molecular modeling study proposed possible interaction between aptamer L5 and heat shock protein 70 (HSP70). SIGNIFICANCE: The target-specificity of PTX-NPL5 towards neoplastic hepatocytes, probably achieved through HSP70 recognition, enhanced its therapeutic efficacy over CF, which may facilitate its real clinical deployment against HCC in the near future.

Recent Approaches and Success of Liposome-Based Nano Drug Carriers for the Treatment of Brain Tumor.

Brain tumors are nothing but a collection of neoplasms that originate either from areas within the brain or from systemic metastasized tumors of other organs spread to the brain. It is a leading cause of death worldwide. The presence of the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), and some other factors may limit the entry of many potential therapeutics into the brain tissues in the tumor area at the therapeutic concentration required for satisfying effectiveness. Liposomes play an active role in delivering many drugs through BBB into the tumor due to their nanosize and physiological compatibility. The surface of the liposomes can be modified with various ligands that are very specific to the numerous receptors overexpressed onto the BBB as well as onto the diseased tumor surface site (i.e., BBTB) to deliver selective drugs into the tumor site. Further, this colloidal carrier can encapsulate both lipophilic and hydrophilic drugs due to its unique structure. Moreover, the enhanced permeability and retention (EPR) effect can be an added advantage for nanosize liposomes to concentrate into the tumor microenvironment through relatively leaky vasculature of solid tumor in the brain where no penetration restriction applies compared to normal BBB. Here in this review, we have tried to compile the recent advancement along with the associated challenges of liposomes containing different anti-cancer chemotherapeutics across the BBB/BBTB for the treatment of gliomas that will be very helpful for the readers for better understanding of different trends of brain tumor targeted liposomes-based drug delivery and for pursuing fruitful research on the similar research domain.

Preferential hepatic uptake of paclitaxel-loaded poly-(d-l-lactide-co-glycolide) nanoparticles - A possibility for hepatic drug targeting: Pharmacokinetics and biodistribution.

Liver cancer is a leading cause of death related to cancer worldwide. Poly(d-l-lactide-co-glycolide) (PLGA) nanoparticles provide prolonged blood residence time and sustained drug release, desirable for cancer treatment. To achieve this, we have developed paclitaxel-loaded PLGA nanoparticles by emulsification solvent evaporation method and evaluated by in vitro and in vivo studies. The results obtained from in vitro study showed that drug loading efficiency was 84.25% with an initial burst release followed by sustained drug release. Cellular uptake and in vitro cytotoxicity of the formulated nanoparticles using HepG2, Huh-7 cancer cells and Chang liver cells were also investigated. The formulated nanoparticles showed more cytotoxic effect at lower concentration and were internalized well by HepG2 cells compared to free-drug and marketed formulation. Prolonged half-life and higher plasma and liver drug concentrations of the formulated nanoparticles were observed as compared to free drug and marketed formulation in rats. Thus, paclitaxel-loaded polymeric nanoparticle has shown its potential for the treatment of liver cancer.

Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor.

Docetaxel (DTX) is found to be very effective against glioma cell in vitro. However, in vivo passage of DTX through BBB is extremely difficult due to the physicochemical and pharmacological characteristics of the drug. No existing formulation is successful in this aspect. Hence, in this study, effort was made to send DTX through blood-brain barrier (BBB) to brain to treat diseases such as solid tumor of brain (glioma) by developing DTX-loaded nanoliposomes. Primarily drug-excipients interaction was evaluated by FTIR spectroscopy. The DTX-loaded nanoliposomes (L-DTX) were prepared by lipid layer hydration technique and characterized physicochemically. In vitro cellular uptake in C6 glioma cells was investigated. FTIR data show that the selected drug and excipients were chemically compatible. The unilamellar vesicle size was less than 50 nm with smooth surface. Drug released slowly from L-DTX in vitro in a sustained manner. The pharmacokinetic data shows more extended action of DTX from L-DTX in experimental rats than the free-drug and Taxotere®. DTX from L-DTX enhanced 100% drug concentration in brain as compared with Taxotere® in 4 h. Thus, nanoliposomes as vehicle may be an encouraging strategy to treat glioma with DTX.

Nanoscale Formulations and Diagnostics With Their Recent Trends: A Major Focus of Future Nanotechnology.

Nanomedicine is an emerging and rapidly growing field, possibly exploring for high expectation to healthcare. Nanoformulations have been designed to overcome challenges due to the development and fabrication of nanostructures. Unique size-dependent properties of nanoformulations make them superior and indispensable in many areas of human activity. Nano drug delivery systems are formulated and engineered to carry and deliver a number of substances in a targeted and controlled way. The vision of nanocarriers can be designed that will serve a dual purpose, allowing both treatment and diagnosis to be contained in an 'all-in-one' package. Nanoscale drugdelivery systems efficiently regulate the release, pharmacokinetics, pharmacodynamics, solubility, immunocompatibility, cellular uptake and biodistribution of chemical entities (drug). Their cellular uptake takes place by various mechanisms such as micropinocytosis, phagocytosis and receptor mediated endocytosis. These phenomena cause longer retention in blood circulation resulting in the release of the encapsulated materials in a sustained manner thus minimize the plasma fluctuations and toxic side effects. In this manner, the therapeutic index of conventional pharmaceuticals is efficiently increased. They can be used to deliver both micro and macro biomolecules such as peptides, proteins, plasmid DNA and synthetic oligodeoxynucleotides. In this present review, several recent developing and modifying nano-products for the detection, analysis, and treatment of diseases with their US and world patents along with various diagnostic kits have been discussed.

Is type 2 diabetes mellitus a predisposal cause for developing hepatocellular carcinoma?

Hepatic cancer stands as one of the frontier causes of cancer related mortality worldwide. Among the several risk factors already established, type 2 diabetes is now considered as one of the important risks in progression of liver cancer. Studies have shown that likelihood of occurrence of liver cancer is many folds higher in patients diagnosed with type II diabetes compared to patients without diabetes. Liver plays an important role in metabolism of glucose in our body, so may be type II diabetes as it is an important epiphenomenon of hepatic diseases such as liver cirrhosis, liver failure, fatty liver, chronic hepatitis and hepatocellular carcinoma. Some reports suggested that extensive change in enzyme structures in molecular level in diabetic patients may lead to liver function damage and hence accelerate hepatic cancer. Other strong links between these two diseases are "non alcoholic fatty liver diseases" and "nonalcoholic steatohepatitis" which are metabolic disorders caused by type II diabetes and eventually develops hepatocellular carcinoma. However, it still remains unanswered whether prevention of diabetes would effectively lower the chances of developing liver cancer or eliminating diabetes from the population would effectively reduce the liver cancer incidence. In this review, we will primarily focus on the molecular link between type2 diabetes and hepatic cancer and investigate underlying mechanism to establish type II diabetes as predisposed cause of hepatic cancer.