Efficacy of pegylated Graphene oxide quantum dots as a nanoconjugate sustained release metformin delivery system in in vitro insulin resistance model.

Metformin, the primary therapy for type 2 diabetes mellitus (T2DM), showed limitations such as varying absorption, rapid system clearance, required large amount, resistance, longstanding side effects. Use of Nano formulations for pharmaceuticals is emerging as a viable technique to reduce negative consequences of drug, while simultaneously attaining precise release and targeted distribution. This study developed a Polyethylene Glycol conjugated Graphene Oxide Quantum dots (GOQD-PEG) nanocomposite for the sustained release of metformin. Herein, we evaluated the effectiveness of metformin-loaded nanoconjugate in in vitro insulin resistance model. Results demonstrated drug loaded nanoconjugate successfully restored glucose uptake and reversed insulin resistance in in vitro conditions at reduced dosage compared to free metformin.

Electrospun Cerium Oxide Nanoparticle/Aloe Vera Extract-Loaded Nanofibrous Poly(Ethylene Oxide)/Polyurethane Mats As Diabetic Wound Dressings.

Currently the prevalence of diabetic wounds brings a huge encumbrance onto patients, causing high disability and mortality rates and a major medical challenge for society. Therefore, in this study, we are targeting to fabricate aloe vera extract infused biocompatible nanofibrous patches to facilitate the process of diabetic wound healing. Additionally, clindamycin has been adsorbed onto the surface of in-house synthesized ceria nanoparticles and again used separately to design a nanofibrous web, as nanoceria can act as a good drug delivery vehicle and exhibit both antimicrobial and antidiabetic properties. Various physicochemical characteristics such as morphology, porosity, and chemical composition of the produced nanofibrous webs were investigated. Bacterial growth inhibition and antibiofilm studies of the nanofibrous materials confirm its antibacterial and antibiofilm efficacy against Gram-positive and Gram-negative bacteria. An in vitro drug release study confirmed that the nanofibrous mat show a sustained drug release pattern (90% of drug in 96 h). The nanofibrous web containing drug loaded nanoceria not only showed superior in vitro performance but also promoted greater wound contraction (95 ± 2%) in diabetes-induced mice in just 7 days. Consequently, it efficaciously lowers the serum glucose level, inflammatory cytokines, oxidative stress, and hepatotoxicity markers as endorsed by various ex vivo tests. Conclusively, this in-house-fabricated biocompatible nanofibrous patch can act as a potential medicated suppository that can be used for treating diabetic wounds in the proximate future.

Biofabrication of aminated nanocellulose reinforced polyvinyl alcohol/chitosan nanofibrous scaffold for sustained release of diltiazem hydrochloride.

In the modern environment conscious era, there has been a huge demand for the effective green method to fabricate biomaterials for sustained transdermal release of diltiazem hydrochloride to treat hypertension and cardiac failure. In this vein, the present study explores the amination of waste jute sourced nanocellulose (ANC) and its effect as a reinforcing filler to design electrospun polyvinyl alcohol (PVA)/chitosan based polymeric nanofibrous scaffold for drug delivery. The characterization results of FTIR (Fourier Transform Infrared Spectroscopy) confirm the successful chemical modification of nanocellulose (NCC). SEM (Scanning Electron Microscopy) results indicate the morphological modifications in ANC due to grafting. ANC enhances the mechanical properties of scaffold and sustains the release of the loaded drug to 67.89±3.39% as compared to the pure PVA/chitosan scaffold of 92.63±4.63% over a period of 72 h as shown by the results of in-vitro drug release study. Moreover, the incorporation of 0.5 % ANC improves the anti-bacterial activity against both gram-positive (97.4±4.87%, reduction in viable cells count) and gram-negative bacteria (98.5±4.93%, reduction in viable cells count). Further, the skin irritation and MTT assay authenticate the biocompatibility of the developed scaffold. The overall findings hence prove the efficacy of the engineered scaffold as a potential transdermal patch for sustained drug delivery applications.

Enhanced Triethylamine Detection at Room Temperature Using a Layered MoS2 Nanosheet-Coated PPy Nanorod: A Comprehensive Study.

The rapid and reliable detection of triethylamine (TEA), a toxic, explosive, volatile organic compound at room temperature, is highly significant for food safety, environmental, and human health monitoring. This manuscript reports a layered molybdenum disulfide (MoS2) nanosheet-coated polypyrrole (PPy) nanorod-based heterostructure sensor (MsPy) which offers superior sensing properties toward TEA at room temperature (25 °C). Herein, different MsPy nanocomposites were synthesized, followed by a controlled sulfidation reaction through dissolution, diffusion, and regrowth mechanisms. Optimizing the ratio of the precursor of molybdenum trioxide (MoO3/PPy) is crucial for achieving effective deposition of a layered MoS2 nanosheet on the PPy surface. The as-prepared MoS2 nanosheet-coated PPy sensor (MsPy_40) enables one to selectively detect trace TEA vapor at 25 °C with a detection lower limit of 0.5 ppm. The MsPy_40 sensor exhibits 17 times higher response than the pristine MoS2 nanosheet to 50 ppm TEA, with rapid response (∼3.9 s) and recovery (∼19.6 s), along with better stability, good selectivity, and remarkable repeatability. The significantly enhanced sensing performance is attributed to the unique surface morphology of the layered MoS2 nanosheet-coated PPy nanorod and the formation of a p-n heterojunction between PPy and MoS2.

Innovative utilization of harvested mushroom substrate for green synthesis of silver nanoparticles: A multi-response optimization approach.

In this work, harvested mushroom substrate (HMS) has been explored for the first time through a comprehensive optimization study for the green synthesis of silver nanoparticles (AgNPs). A multiple response central composite design with three parameters: pH of the reaction mixture, temperature, and incubation period at three distinct levels was employed in the optimization study. The particle size of AgNPs, UV absorbance, and the percentage of Ag/Cl elemental ratio were considered as the response parameters. For each response variable examined the model used was found to be significant (P < 0.05). The ideal conditions were: pH 8.9, a temperature of 59.4 °C, and an incubation period of 48.5 h. The UV-visible spectra of AgNPs indicated that the absorption maxima for AgNP-3 were 414 nm, 420 for AgNPs-2, and 457 for AgNPs-1. The XRD analysis of AgNPs-3 and AgNPs-2 show a large diffraction peak at ∼38.2°, ∼44.2°, ∼64.4°, and ∼77.4°, respectively, which relate to the planes of polycrystalline face-centered cubic (fcc) silver. Additionally, the XRD result of AgNPs-1, reveals diffraction characteristics of AgCl planes (111, 200, 220, 311, 222, and 400). The TEM investigations indicated that the smallest particles were synthesized at pH 9 with average diameters of 35 ± 6 nm (AgNPs-3). The zeta potentials of the AgNPs are -36 (AgNPs-3), -28 (AgNPs-2), and -19 (AgNPs-1) mV, respectively. The distinct IR peak at 3400, 1634, and 1383 cm-1 indicated the typical vibration of phenols, proteins, and alkaloids, respectively. The AgNPs were further evaluated against gram (+) strain Bacillus subtilis (MTCC 736) and gram (-) strain Escherichia coli (MTCC 68). All of the NPs tested positive for antibacterial activity against both bacterial strains. The study makes a sustainable alternative to disposing of HMS to achieve the Sustainable Development Goals (SDGs).

3-Polythiophene Acetic Acid Nanosphere Anchored Few-Layer Graphene Nanocomposites for Label-Free Electrochemical Immunosensing of Liver Cancer Biomarker.

This study devised a label-free electrochemical immunosensor for the quantitative detection of alpha-fetoprotein (AFP). 3-Polythiophene acetic acid (3-PTAA) nanoparticles were anchored onto a few-layer graphene (FLG) nanosheet, and the resulting nanocomposite was utilized as the immunosensor platform. The AFP antibody (anti-AFP) was immobilized on 3-PTAA@FLG via a covalent interaction between the amine group of anti-AFP and the carboxylic group of 3-PTAA via ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling. FLG is largely responsible for providing electrochemical signals, whereas 3-PTAA nanoparticles are well-known for their ability to be compatible with biological molecules in neutral aqueous solutions. Moreover, the carboxyl group present in 3-PTAA effectively binds anti-AFP through EDC/NHS conjugation. Owing to good dispersibility and higher surface area of 3-PTAA, it is very convenient for casting the polymer directly on the electrode substrate followed by immobilization of anti-AFP. Thus, it is feasible to regulate the activity of AFP proteins and control the spatial distribution of the immobilized anti-AFP proteins. The electrochemical sensing performance was assessed via cyclic voltammetry and electrochemical impedance spectroscopy. For an increase in the bioconjugate concentration, the results demonstrated a surge in charge-transfer resistance and a consequent decline in the current response. This approach effectively detected AFP at an extended dynamic range of 0.0001-250 ng/mL with a detection limit of 0.047 pg/mL. Furthermore, the sensing capacity of the immunosensor for AFP detection has been demonstrated to be steady in real human serum cultures. Our approach exhibits good electrochemical performance in terms of reproducibility, selectivity, and stability, which would surely impart budding applications in the clinical diagnosis of several other tumor markers.

Two cases of Rapunzel syndrome in adult males.

Trichobezoar are foreign bodies formed from undigested hairs that accumulate in the gastrointestinal tract and cause obstruction. Trichobezoar are usually found in the stomach but when the tail of the bezoar extends into the small intestine it is referred to as Rapunzel syndrome. Patients are usually females and have a history of psychiatric illness. However, in this study, we present two cases of Rapunzel syndrome in adult male patients that were managed with surgery. Trichobezoar should be considered in all patients with a history of psychiatric illness presenting with abdominal symptoms regardless of gender.

Asymmetric fabrication and in vivo evaluation of the wound healing potency of electrospun biomimetic nanofibrous scaffolds based on collagen crosslinked modified-chitosan and graphene oxide quantum dot nanocomposites.

Asymmetric scaffolds were developed through electrospinning by utilizing biocompatible materials for effective wound healing applications. First of all, the chitosan surface was modified with decanoyl chloride and crosslinked with collagen to synthesize collagen crosslinked modified-chitosan (CG-cross-CS-g-Dc). Then, the asymmetric scaffolds were fabricated through electrospinning, where the top layer was a monoaxial nanofiber of the PCL/graphene oxide quantum dot (GOQD) nanocomposite and the bottom layer was a coaxial nanofiber having PCL in the core and the CG-cross-CS-g-Dc/GOQD nanocomposite in the shell layer. The formation of monoaxial (∼130 ± 50 nm) and coaxial (∼320 ± 40 nm) nanofibers was confirmed by transmission electron microscopy (TEM). The presence of GOQDs contributed to antioxidant and antimicrobial efficacy. These scaffolds showed substantial antibacterial activity against the common wound pathogens Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The scaffolds exhibited excellent cytocompatibility (MTT assay) and anti-inflammatory behaviour as analysed via the cytokine assay and biochemical analysis. The in vivo wound healing potential of the nanofibrous scaffolds was assessed with full-thickness excisional wounds in a rat model. The scaffolds accelerated the re-epithelialization as well as the collagen deposition, thereby facilitating the wound healing process in a very short span of time (10 days). Both in vitro and in vivo analyses thus provide a compelling argument for the use of these scaffolds as therapeutic biomaterials and their suitability for application in rapid wound regeneration and repair.

Integration of 3D Printing-Coelectrospinning: Concept Shifting in Biomedical Applications.

Porous structures with sizes between the submicrometer and nanometer scales can be produced using efficient and adaptable electrospinning technology. However, to approximate desirable structures, the construction lacks mechanical sophistication and conformance and requires three-dimensional solitary or multifunctional structures. The diversity of high-performance polymers and blends has enabled the creation of several porous structural conformations for applications in advanced materials science, particularly in biomedicine. Two promising technologies can be combined, such as electrospinning with 3D printing or additive manufacturing, thereby providing a straightforward yet flexible technique for digitally controlled shape-morphing fabrication. The hierarchical integration of configurations is used to imprint complex shapes and patterns onto mesostructured, stimulus-responsive electrospun fabrics. This technique controls the internal stresses caused by the swelling/contraction mismatch in the in-plane and interlayer regions, which, in turn, controls the morphological characteristics of the electrospun membranes. Major innovations in 3D printing, along with additive manufacturing, have led to the production of materials and scaffold systems for tactile and wearable sensors, filtration structures, sensors for structural health monitoring, tissue engineering, biomedical scaffolds, and optical patterning. This review discusses the synergy between 3D printing and electrospinning as a constituent of specific microfabrication methods for quick structural prototypes that are expected to advance into next-generation constructs. Furthermore, individual techniques, their process parameters, and how the fabricated novel structures are applied holistically in the biomedical field have never been discussed in the literature. In summary, this review offers novel insights into the use of electrospinning and 3D printing as well as their integration for cutting-edge applications in the biomedical field.

Hyaluronic acid-graphene oxide quantum dots nanoconjugate as dual purpose drug delivery and therapeutic agent in meta-inflammation.

Type 2 diabetes mellitus (T2DM) predominantly considered a metabolic disease is now being considered an inflammatory disease as well due to the involvement of meta-inflammation. Obesity-induced adipose tissue inflammation (ATI) is one of the earliest phenomena in the case of meta-inflammation, leading to the advent of insulin resistance (IR) and T2DM. The key events of ATI are orchestrated by macrophages, which aggravate the inflammatory state in the tissue upon activation, ultimately leading to systemic chronic low-grade inflammation and Non-Alcoholic Steatohepatitis (NASH) through the involvement of proinflammatory cytokines. The CD44 receptor on macrophages is overexpressed in ATI, NASH, and IR. Therefore, we developed a CD44 targeted Hyaluronic Acid functionalized Graphene Oxide Quantum Dots (GOQD-HA) nanocomposite for tissue-specific delivery of metformin. Metformin-loaded GOQD-HA (GOQD-HA-Met) successfully downregulated the expression of proinflammatory cytokines and restored antioxidant status at lower doses than free metformin in both palmitic acid-induced RAW264.7 cells and diet induced obese mice. Our study revealed that the GOQD-HA nanocarrier enhanced the efficacy of Metformin primarily by acting as a therapeutic agent apart from being a drug delivery platform. The therapeutic properties of GOQD-HA stem from both HA and GOQD having anti-inflammatory and antioxidant properties respectively. This study unravels the function of GOQD-HA as a targeted drug delivery option for metformin in meta-inflammation where the nanocarrier itself acts as a therapeutic agent.

Improved Ethanol Sensing Performance of α-MnO2 Nanorods at Room Temperature Enabled through PPy Embedding.

Ethanol is a colorless, highly flammable, volatile organic compound and is a biomarker for fatty liver diseases. So, high-performance and reliable ethanol sensors are the need of the day for biomedical and environmental monitoring applications and drunken driving detection. In this work, we have reported a polypyrrole (PPy)-embedded α-MnO2 nanorod (NR)-based chemiresistive sensor for the selective detection of trace ethanol vapor at room temperature (25 °C). PPy-embedded α-MnO2 NR nanocomposites (MP25, MP50, and MP100) were synthesized by in situ chemical oxidative polymerization of pyrrole followed by mixing of α-MnO2 NR having different weight ratios. The prepared nanocomposites were characterized by various sophisticated instruments such as XRD, FTIR, Raman spectroscopy, BET, FESEM, TEM, EDX, UV-vis spectroscopy, and current-voltage (I-V) measurement. The as-prepared sensor, namely, PPy-embedded α-MnO2 nanorod (MP50), shows the highest response to ethanol vapor with a detection lower limit of 1 ppm at room temperature with rapid response (∼2.39 s) and recovery (∼37.08 s) times associated with at least 60 days stability, excellent selectivity, good repeatability, and reproducibility. The formation of a p-n heterojunction and transfer of charge carriers between PPy and MnO2 nanoparticles are attributed to the enhancement of sensing performance. Thus, the prepared sensor could be potentially applicable to detect ethanol content in alcoholic beverages, diagnose liver disease from exhale breath analysis, and drunken driving detection.

Prospects of 2D graphdiynes and their applications in desalination and wastewater remediation.

Water is an indispensable part of human life that affects health and food intake. Water pollution caused by rapid industrialization, agriculture, and other human activities affects humanity. Therefore, researchers are prudent and cautious regarding the use of novel materials and technologies for wastewater remediation. Graphdiyne (GDY), an emerging 2D nanomaterial, shows promise in this direction. Graphdiyne has a highly symmetrical π-conjugated structure consisting of uniformly distributed pores; hence, it is favorable for applications such as oil-water separation and organic-pollutant removal. The acetylenic linkage in GDY can strongly interact with metal ions, rendering GDY applicable to heavy-metal adsorption. In addition, GDY membranes that exhibit 100% salt rejection at certain pressures are potential candidates for wastewater treatment and water reuse via desalination. This review provides deep insights into the structure, properties, and synthesis methods of GDY, owing to which it is a unique, promising material. In the latter half of the article, various applications of GDY in desalination and wastewater treatment have been detailed. Finally, the prospects of these materials have been discussed succinctly.

Nanotherapeutic potential of antibacterial folic acid-functionalized nanoceria for wound-healing applications.

Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10-20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.

The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.

Ameliorative effects of clindamycin - nanoceria conjugate: A ROS responsive smart drug delivery system for diabetic wound healing study.

BACKGROUND: Increased incidence of antibiotic-resistant species calls for development of new types of nano-medicine that can be used for healing of bacteria-caused wounds, such as diabetic foot ulcer. As diabetic patients have inefficient defense mechanism against reactive oxygen species (ROS) produced in our body as a by-product of oxygen reduction, the process of wound healing takes longer epithelialisation period. Ceria nanoparticles (CNPs) are well-known for their antibacterial and ROS-scavenging nature. Yet till now no significant effort has been made to conjugate ceria nanoparticles with drugs to treat diabetic wounds. METHODS: In this experiment, CNPs were synthesized in-house and clindamycin hydrochloride was loaded onto it by physical adsorption method for reactive oxygen species responsive drug delivery. Various physico-chemical characterisations such as Transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Energy dispersive X-ray, Thermogravimetric study etc. were performed to affirm the formation of both nanoceria along with drug encapsulated nanoceria. RESULTS: Both of these as-prepared formulations inhibited the growth of Gram-positive as well as Gram-negative bacteria confirmed by Disk diffusion study; exhibiting their antibacterial effect. In-vitro drug release study was carried out in physiological environment both in absence and presence of hydrogen peroxide solution to test the reactive ROS-responsiveness of the drug loaded nanocomposites. It also exhibited faster wound healing in diabetes-induced rats. Therefore, it could successfully lower the amount of serum glucose level, inflammation cytokines, hepatotoxic and oxidative stress markers in diabetic rats as confirmed by various ex vivo tests conducted. CONCLUSION: Thus, drug loaded ceria nanoparticles have the potential to heal diabetic wounds successfully and can be considered to be useful for the fabrication of appropriate medicated suppositories beneficial for diabetic foot ulcer treatment in future.

Transdermal therapeutic system: Study of cellulose nanocrystals influenced methylcellulose-chitosan bionanocomposites.

Over the past few years, there is a drive toward the fabrication and application of bio-based non-cytotoxic drug carriers. Cellulose nanocrystals (CNCs) have gotten immense research attention as a promising bioderived material in the biomedical field due to its remarkable properties. The delivery of analgesic and anti-inflammatory drug, ketorolac tromethamine (KT) by transdermal route is stipulated herewith to fabricate suitable transdermal therapeutic systems. We have synthesized CNCs from jute fibers and aim to develop a non-cytotoxic polymer-based bionanocomposites (BNCs) transdermal patch, formulated with methylcellulose (MC), chitosan (CH), along with exploration of CNCs for sustained delivery of KT, where CNCs act as nanofiller and elegant nanocarrier. CNCs reinforced MCCH blends were prepared via the solvent evaporation technique. The chemical structure, morphology, and thermal stability of the prepared bionanocomposites formulations were studied by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), TGA, DSC, DMA, and SEM. The In vitro drug release studies were executed using Franz diffusion cells. The BNC patches showed in-vitro cytocompatibility and the drug release study revealed that BNC containing 1 wt% CNCs presented the best-sustained drug release profile. The bioderived CNCs appear to enhance the BNCs drug's bioavailability, which could have a broad prospect for TDD applications.

Development of an Efficient Immunosensing Platform by Exploring Single-Walled Carbon Nanohorns (SWCNHs) and Nitrogen Doped Graphene Quantum Dot (N-GQD) Nanocomposite for Early Detection of Cancer Biomarker.

In this work, a novel electrochemical immunosensor based on nitrogen doped graphene quantum dot (N-GQD) and single-walled carbon nanohorns (SWCNHs) was developed for the detection of α-fetoprotein (AFP), a cancer biomarker. Thus, to fabricate the platform of the immunosensor, nanocomposite architecture was developed by decorating N-GQD on the surface of the SWCNHs. The resulting hybrid architecture (N-GQD@SWCNHs) functioned as an exceptional base for the immobilization of antibody (Anti-AFP) through carbodiimide reaction with good stability and bioactivity. The immunosensor was prepared by evenly distributing the bioconjugates (N-GQD@SWCNHs/Anti-AFP) dispersion on the surface of the glassy carbon electrode, and subsequently blocking the remaining active sites by bovine serum albumin to prevent the nonspecific adsorption. Cyclic voltammetry and electrochemical impedance spectroscopy technique was employed to investigate the assembly process of the immunosensor. Under optimal conditions, the immunosensor exhibited a broad dynamic range in between 0.001 ng/mL to 200 ng/mL and a low detection limit of 0.25 pg/mL. Furthermore, the sensor showed high selectivity, desirable stability, and reproducibility. Measurements of AFP in human serum gave outstanding recovery within 99.2% and 102.1%. Thus, this investigation and the amplification strategy exhibited a potential role of the developed nanocomposite based sensor for early clinical screening of cancer biomarkers.

Apigenin-loaded galactose tailored PLGA nanoparticles: A possible strategy for liver targeting to treat hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy worldwide. Recent reports focusing on the efficacy of apigenin-loaded nanoparticles (NPs) in combating the progress of HCC encouraged us to develop galactose-tailored PLGA NPs loaded with apigenin (API-GAL-NPs) for active liver targeting to treat HCC. Two kinds of apigenin NPs, such as apigenin-PLGA NPs (API-NPs) and API-GAL-NPs were fabricated and characterized by size, surface morphology, encapsulation efficacy, and in vitro drug release kinetics. In vitro assays were performed on HepG2 cells to check the cellular internalization, cytotoxic potential, and apoptotic potential of free apigenin (API), API-NPs, and API-GAL-NPs. In this stdy, API-GAL-NPs exhibited improved cellular internalization of API resulting in significantly high cytotoxic and apoptotic potentials to HepG2 cells over API and API-NPs. In in vivo studies, API-GAL-NPs exhibited a better protective effect against DEN-induced HCC in rats evidenced by the significant reduction of nodule formation, downregulation of matrix metalloproteinases (MMP-2 and MMP-9), and induction of apoptosis in the liver than API and API-NPs. Histopathological studies and scintigraphic imaging also confirmed that API-GAL-NPs treatment achieved better therapeutic efficacy against DEN-induced HCC in rats over API-NPs. In conclusion, API-GAL-NPs may serve as a potential therapeutic agent against HCC in the future by achieving improved liver targeting.

Apigenin-Loaded PLGA-DMSA Nanoparticles: A Novel Strategy to Treat Melanoma Lung Metastasis.

The flavone apigenin (APG), alone as well as in combination with other chemotherapeutic agents, is known to exhibit potential anticancer effects in various tumors and inhibit growth and metastasis of melanoma. However, the potential of apigenin nanoparticles (APG-NPs) to prevent lung colonization of malignant melanoma has not been well investigated. APG-loaded PLGA-NPs were surface-functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) for the treatment of melanoma lung metastasis. DMSA-conjugated APG-loaded NPs (DMSA-APG-NPs) administered by an oral route exhibited sustained APG release and showed considerable enhancement of plasma half-life, Cmax value, and bioavailability compared to APG-NPs both in plasma and the lungs. DMSA-conjugated APG-NPs showed comparably higher cellular internalization in B16F10 and A549 cell lines compared to that of plain NPs. Increased cytotoxicity was observed for DMSA-APG-NPs compared to APG-NPs in A549 cells. This difference between the two formulations was lower in B16F10 cells. Significant depolarization of mitochondrial transmembrane potential and an enhanced level of caspase activity were observed in B16F10 cells treated with DMSA-APG-NPs compared to APG-NPs as well. Western blot analysis of various proteins was performed to understand the mechanism of apoptosis as well as prevention of melanoma cell migration and invasion. DMSA conjugation substantially increased accumulation of DMSA-APG-NPs given by an intravenous route in the lungs compared to APG-NPs at 6 and 8 h. This was also corroborated by scintigraphic imaging studies with radiolabeled formulations administered by an intravenous route. Conjugation also allowed comparatively higher penetration as evident from an in vitro three-dimensional tumor spheroid model study. Finally, the potential therapeutic efficacy of the formulation was established in experimental B16F10 lung metastases, which suggested an improved bioavailability with enhanced antitumor and antimetastasis efficacy of DMSA-conjugated APG-NPs following oral administration.

Rare case of a patient with symptomatic Meckel's diverticulum enteroliths.

A 61-year-old man presented with non-specific abdominal symptoms, including left groin pain and change in bowel habits. Investigations revealed a cystic lesion, containing numerous irregular calcifications, with the primary differential being a dermoid cyst containing teeth-like calcifications. At laparoscopy it was found to be a Meckel's diverticulum, containing a large number of enteroliths. This case revealed the importance of considering enteroliths in patients with imaging showing intra-abdominal calcifications, and laparoscopy for diagnosis and treatment.