Polycyclic aromatic hydrocarbon and its effects on human health: An overeview.

Polycyclic aromatic hydrocarbons (PAHs) are a class of chemicals of considerable environmental significance. PAHs are chemical contaminants of fused carbon and hydrogen aromatic rings, basically white, light-yellow, or solid compounds without color. Natural sources of pollution are marginal or less significant, such as volcanic eruptions, natural forest fires, and moorland fires that trigger lightning bursts. The significant determinants of PAH pollution are anthropogenic pollution sources, classified into four groups, i.e., industrial, mobile, domestic, and agricultural pollution sources. Humans can consume PAHs via different routes, such as inhalation, dermal touch, and ingestion. The Effect of PAHs on human health is primarily based on the duration and route of exposure, the volume or concentration of PAHs to which one is exposed, and the relative toxicity of PAHs. Many PAHs are widely referred to as carcinogens, mutagens, and teratogens and thus pose a significant danger to human health and the well-being of humans. Skin, lung, pancreas, esophagus, bladder, colon, and female breast are numerous organs prone to tumor development due to long-term PAH exposure. PAH exposure may increase the risk of lung cancer as well as cardiovascular disease (CVD), including atherosclerosis, thrombosis, hypertension, and myocardial infarction (MI). Preclinical studies have found a relationship between PAH exposure, oxidative stress, and atherosclerosis. In addition, investigations have discovered a relationship between PAH exposure at work and CVD illness and mortality development. This review aims to explain PAH briefly, its transportation, its effects on human health, and a relationship between environmental exposures to PAHs and CVD risk in humans.

Micro and nanorobot-based drug delivery: an overview.

Progress in the drug delivery system in the last few decades has led to many advancements for efficient drug delivery. Both micro and nanorobots, are regarded as superior drug delivery systems to deliver drugs efficiently by altering other forms of energy into propulsion and movements. Furthermore, it can be advantageous as it is directed to targeted sites beneath physiological environments and conditions. They have been validated to possess the capability to encapsulate, transport, and supply therapeutic contents directly to the disease sites, thus enhancing the therapeutic efficiency and decreasing systemic side effects of the toxic drugs. This review discusses about the microand nanorobots for the diagnostics and management of diseases, types of micro, and nanorobots, role of robots in drug delivery, and its biomedical applications.

Fabrication, in vitro and ex vivo evaluation of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein.

The present study is associated with the development of proliposomes and liposomal derived gel for enhanced solubility and permeability of diacerein. Proliposomes were developed by thin film hydration method and converted into the liposomal derived gel using carbopol-934 as a gelling agent. Formulations with varied lecithin to cholesterol ratios were investigated to obtain the optimal size, entrapment efficiency, and enhanced in vitro dissolution. Dynamic light scattering analysis revealed the particle size and zeta potential in the range of 385.1±2.45-762.8±2.05 nm and -22.4±0.55-31.2±0.96mV respectively. Fourier transform infrared (FTIR) spectroscopic analysis depicted the physicochemical compatibility, powdered x-ray diffraction (PXRD) analysis predicted the crystalline nature of pure drug and its transition into amorphous form within formulation. The differential scanning calorimetry (DSC) demonstrated the thermal stability of the formulation. The in vitro drug release study using dialysis membrane displayed the enhanced dissolution of diacerein due to the presence of hydrophilic carrier (Maltodextrin) followed by sustained drug release due to the presence of lipid mixture (lecithin and cholesterol). Ex vivo permeation studies depicted 3.50±0.27 and 3.21±0.22 folds enhanced flux of liposomal gels as compared to control. The acute oral toxicity study showed safety and biocompatibility of the system as no histopathological changes in vital organs were observed. These results suggests that proliposomes and liposomal derived gel are promising candidates for the solubility and permeability enhancement of diacerein in the management of osteoarthritis.

Lipid poly (ɛ-caprolactone) hybrid nanoparticles of 5-fluorouracil for sustained release and enhanced anticancer efficacy.

AIMS: The present study aimed to develop and characterize poly (ɛ-caprolactone) (PCL) based lipid polymer hybrid nanoparticles for sustained delivery and in-vitro anti-cancer activity in MCF-7 and HeLa cells cancer cell line. MATERIALS AND METHODS: The nanoprecipitation method was used for the development of 5-fluorouracil loaded lipid polymer hybrid nanoparticles (LPHNPs). The developed LPHNPs were characterized for physicochemical characteristics and the anti-cancer effect was evaluated in MCF-7 and HeLa cells. SIGNIFICANT FINDINGS: Six formulations having fixed amount of drug and varied lipid, polymer and emulsifier concentrations were prepared. The particle size was in the range of 174 ± 4 to 267 ± 2.65 nm, entrapment efficiency (92.87 ± 0.594 to 94.13 ± 0.772%), negative zeta potential, optimum polydispersity index and spherical shape. FTIR analysis shows no chemical interaction among the formulation components, DSC analysis reveals the disappearance of 5-FU melting endotherm in the developed LPHNPs suggesting amorphization of 5-FU in the developed system, XRD analysis indicates successful encapsulation of the drug in the lipid polymer matrix. The in-vitro release shows a biphasic release pattern with an initial burst release followed by a sustained release profile for 72 h. The drug loaded LPHNPs exhibited a greater cytotoxic effect than 5-FU solution due to sustained release and increased cellular internalization. The acute toxicity study revealed the safety of the developed carrier system for potential delivery of chemotherapeutic agents. SIGNIFICANCE: The developed LPHNPs of 5-fluorouracil will provide the sustained release behavior of 5-fluorouracil to maximize the therapeutic efficacy and minimize the dose related toxicity.

Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization.

Pentazocine (PTZ) is a narcotic analgesic used to manage moderate to severe, acute and chronic pains. In this study, PTZ loaded Ethyl cellulose microsphere has been formulated for sustained release and improved bioavailability of PTZ. These microspheres were fabricated by oil in water emulsion solvent evaporation technique. A three factorial, three levels Box-Behnken design was applied to investigate the influence of different formulation components and process variables on the formulation response using the numeric approach through the design expert® software. All the formulations were characterized for the morphology, different physicochemical properties and the results were supported with the ANOVA analysis, three dimensional contour graphs and regression equations. The maximum percentage yield was 98.67% with 98% entrapment of PTZ. The mean particle size of the formulations ranges from 50-148µm, which directly relates to the concentration of polymer and inversely proportional to the stirring speed. SEM revealed the spherical shape of PTZ microspheres with porous structures. These are physically, chemically and thermally stable as confirmed through Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD) and thermal gravimetric (TG) analysis respectively. The microspheres provided a sustained release of the PTZ for more than 12 hours, following zero order with fickian and non fickian diffusion. The results indicate that prepared microspheres can be a potential drug delivery system (DDS) for the delivery of PTZ in the management of pains.

Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting.

The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.

In vitro anti-leukemic assessment and sustained release behaviour of cytarabine loaded biodegradable polymer based nanoparticles.

AIMS: The study aimed to develop, characterize, and evaluate poly (ɛ-caprolactone) (PCL) based nanoparticles for the sustained release behaviour of cytarabine and to investigate the in vitro anti-cancer influence on KG-1 leukemic cell line. MATERIALS AND METHODS: Nanoprecipitation method was used for the preparation of cytarabine loaded PCL nanoparticles. The developed nanoparticles were characterized for physicochemical properties and the anti-leukemic effect on the KG-1 cell line was evaluated. KEY FINDINGS: A total number of five formulations were prepared with size range from 120.5 ± 1.18 to 341.5 ± 3.02, entrapment efficiency (41.31 ± 0.49 to 62.28 ± 0.39%), spherical morphology, negative zeta potentials, considerable particle size distribution, compatibility between the drug and excipients and thermal stability. X-ray diffraction analysis confirmed the successful incorporation of cytarabine in PCL polymer. In vitro drug release in phosphate buffer saline (pH 7.4) showed initial burst release followed by sustained release up to 48 h. The sustained release behaviour efficiently increased the toxicity of cytarabine-loaded PCL nanoparticles to KG-1 (leukemic) and MCF-7 (breast cancer) cell lines in time dependent manner with lower IC50 values than that of drug solution. The flow cytometry study revealed the better apoptotic activity of cytarabine loaded PCL nanoparticle against treated KG-1 cell line. The western blot analysis confirmed the upregulation of cleaved caspase-3 and downregulation of Bcl-2 protein. SIGNIFICANCE: The experimental results suggest that cytarabine loaded PCL nanoparticles is an efficient carrier to prevent the dose associated toxicity while providing sustained release pattern to ensure maximum anti-cancer influence.

Ionically Cross-Linked Chitosan Nanoparticles for Sustained Delivery of Docetaxel: Fabrication, Post-Formulation and Acute Oral Toxicity Evaluation.

INTRODUCTION: Polymeric nanoparticles are potential carriers for the efficient delivery of hydrophilic and hydrophobic drugs due to their multifaceted applications. Docetaxel is relatively less hydrophobic and twice as potent as paclitaxel. Like other taxane chemotherapeutic agents, docetaxel is not well tolerated and shows toxicity in the patients. Nanoencapsulation of potent chemotherapeutic agents has been shown to improve tolerability and therapeutic outcome. Therefore, the present study was designed to fabricate chitosan and sodium tripolyphosphate (STPP) based on ionically cross-linked nanoparticles for sustained release of docetaxel. METHODS: Nanoparticles were prepared by the ionic-gelation method by dropwise addition of the STPP solution into the chitosan solution in different ratios. CNPs were characterized for post-formulation parameters like size, zeta potential, scanning electron microscope (SEM), FTIR, DSC/TGA, pXRD, and in-vitro drug release, as well as for acute oral toxicity studies in Wistar rats. RESULTS AND DISCUSSION: The optimized docetaxel loaded polymeric nanoparticles were in the size range (172.6nm-479.65 nm), and zeta potential (30.45-35.95 mV) required to achieve enhanced permeation and retention effect. In addition, scanning electron microscopy revealed rough and porous surface, whereas, FTIR revealed the compatible polymeric nanoparticles. Likewise, the thermal stability was ensured through DSC and TG analysis, and powder X-ray diffraction analysis exhibited solid-state stability of the docetaxel loaded nanoparticles. The in-vitro drug release evaluation in phosphate buffer saline (pH 7.4) showed sustained release pattern, i.e. 51.57-69.93% within 24 hrs. The data were fitted to different release kinetic models which showed Fickian diffusion as a predominant release mechanism (R2 = 0.9734-0.9786, n= 0.264-0.340). Acceptable tolerability was exhibited by acute oral toxicity in rabbits and no abnormality was noted in growth, behavior, blood biochemistry or histology and function of vital organs. CONCLUSION: Ionically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel.

Enhancement of Dissolution and Skin Permeability of Pentazocine by Proniosomes and Niosomal Gel.

Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the oral bioavailability, stability, and topical permeability of therapeutic agents. The low solubility and low oral bioavailability due to extensive first pass metabolism make Pentazocine as an ideal candidate for oral and topical sustained release delivery. The present study was aimed to formulate the PNs by quick slurry method that are converted to niosomes (liquid dispersion) by hydration, and subsequently formulated to semisolid niosomal gel. The PNs were found in spherical shape in the SEM and stable in the physicochemical and thermal analysis (FTIR, TGA, and XRD). The quick slurry method produced high recovery (> 80% yield) and better flow properties (θ = 28.1-37.4°). After hydration, the niosomes exhibited desirable entrapment efficiency (44.45-76.23%), size (4.98-21.3 µm), and zeta potential (- 9.81 to - 21.53 mV). The in vitro drug release (T100%) was extended to more than three half-lives (2-4 h) and showed good fit to Fickian diffusion indicated by Korsmeyer-Peppas model (n = 0.136-0.365 and R2 = 0.9747-0.9954). The permeation of niosomal gel was significantly enhanced across rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found promising candidates for oral as dissolution enhancement and sustained release for oral and topical delivery of pentazocine for the management of cancer pain.

Non-invasive strategies for targeting the posterior segment of eye.

The safe and effective treatment of eye diseases has been remained a global myth. Several advancements have been done and various drug delivery and treatment techniques have been suggested. The Posterior segment disorders are the leading cause of visual impairments and blindness. Targeting the therapeutic agents to the anterior and posterior segments of the eye has attracted extensive attention from the scientific community. Significant key factors in the success of ocular therapy are the development of safe, effective, economic and non-invasive novel drug delivery systems. These specialized non-invasive ocular drug delivery systems revolutionized the drug delivery strategies by overcoming the limitations, provided targeted delivery to the ocular tissues by avoiding larger doses, and reducing the toxicity encountered by the conventional approaches. These non-invasive systems are fabricated by ingredients encompassing biodegradability, biocompatibility, mucoadhesion, solubility and permeability enhancement and stimuli responsiveness. The variety of routes are utilized to provide minimally invasive drug delivery to the patients without any discomfort and pain. This review is focused on the brief introduction, types, significance, preparation techniques, components and mechanism of drug release of non-invasive systems, including in situ gelling systems, microspheres, iontophoresis, nanoparticles, nanosuspensions and specialized novel emulsions.

Anti-inflammatory, analgesic and antipyretic activities of Physalis minima Linn.

In our present investigation, the crude methanol extract and chloroform fraction of the whole plant of Physalis minima Linn (Solanaceae) was investigated for anti-inflammatory, analgesic and antipyretic activities in NMRI mice and Wistar rats of either sex at 200 and 400 mg/kg, respectively. Various established in-vivo model's were used during the study. Both crude extract and chloroform fraction showed marked anti-inflammatory and analgesic activities as compared to a control at tested doses. The antipyretic potential of the crude extract and chloroform were insignificant in the Brewer's yeast fever model. Therefore, the whole plant of Physalis minima Linn could be considered as a potential candidate for bioactivity-guided isolation of natural anti-inflammatory and analgesic agents.