A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

The currently available management strategies for acute pancreatitis are inadequately effective which calls for exploration of new approaches to treat this condition. Caffeic acid phenethyl ester (CAPE) is a major bioactive constituent of honeybee propolis with promising therapeutic and preventive applications. However, its pharmaceutical potential and clinical use are hindered by its poor water solubility and limited plasma stability. In this study, we aimed to prepare, characterize and evaluate a CAPE-loaded nanoliposomal formulation to improve the efficacy of CAPE for the management of acute pancreatitis. The CAPE-loaded nanoliposomes (CAPE-loaded-NL) were prepared by a thin layer evaporation technique and were optimized using three edge activators. CAPE-loaded-NL were characterized for their vesicle size (VS), zeta potential (ZP), encapsulation efficiency (EE), polydispersity index (PDI), crystalline state and morphology. The protective effect of the optimal CAPE-loaded-NL was evaluated in a rat model of acute pancreatitis induced by administering a single intraperitoneal injection of L-ornithine. Oral pretreatment with CAPE-loaded-NL significantly counteracted ornithine-induced elevation in serum activities of pancreatic digestive enzymes and pancreatic levels of malondialdehyde, nuclear factor kappa B (NF-κB) p65, tumor necrosis factor-alpha, nitrite/nitrate, cleaved caspase-3 and myeloperoxidase activity. Moreover, pretreatment with CAPE-loaded-NL significantly reinstated the ornithine-lowered glutathione reductase activity, glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 levels and ATP/ADP ratio, and potentiated the Bcl-2/Bax ratio in pancreatic tissue. CAPE-loaded-NL displayed superior antioxidant, anti-inflammatory and anti-apoptotic effects compared to free CAPE oral suspension and achieved a more potent correction of the derangements in serum amylase and pancreatic myeloperoxidase activities. The histological observations were in line with the biochemical findings. Our results suggest that CAPE-loaded-NL provide a promising interventional approach for acute pancreatitis mainly through the enhancement of the exerted antioxidant, anti-inflammatory and anti-apoptotic effects which may be mediated, at least in part, through modulation of Nrf2 and NF-κβ signaling

Determination of cytocompatibility and osteogenesis properties of in situ forming collagen-based scaffolds loaded with bone synthesizing drug for bone tissue engineering

Bone tissue engineering using in situ forming 3D scaffolds can be an alternative to surgically treated scaffolds. This work aimed to develop in situ forming scaffolds using poly (lactic-co-glycolic acid) and a bone synthesizing drug (risedronate) with or without the porogenic agent (collagen). Hybrid scaffolds were formed through solvent-induced phase inversion technique and were morphologically evaluated using scanning electron microscopy (SEM). The effect of scaffolds on Saos-2 cell line viability using 3-(4,5- dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test besides their effect on cell growth using fluorescence microscope was assessed. Furthermore, alkaline phosphatase (ALP) activity as well as Ca2þ deposition on the scaffolds was evaluated. SEM images revealed the porous structure for collagen-based scaffolds. Saos-2 cell proliferation was significantly enhanced with risedronate-loaded scaffolds compared to those lacking the drug. Porous collagen-based scaffolds were more favorable for both the cell growth and the promotion of ALP activity. Furthermore, collagen-based scaffolds promoted the Ca2þ deposition compared to their counterparts without collagen. Such results suggest that collagen-based scaffolds offer excellent biocompatibility for bone regeneration, where this biocompatible nature of scaffold leads to the proliferation of cells that lead to the deposition of mineral on the scaffold. Such in situ forming 3D scaffolds provide a promising noninvasive approach for bone tissue engineering

Visible Light-Driven Photocatalytic Degradation of Ciprofloxacin, Ampicillin and Erythromycin by Zinc Ferrite Immobilized on Chitosan

This study investigated the synthesis of zinc ferrite immobilized on chitosan (ZnFe2O4@Chitosan) and its application in the photodegradation of ciprofloxacin (CIP), ampicillin (AMP) and erythromycin (ERY) in aqueous solution. Results from Fourier transform infrared spectroscopy (FTIR) revealed peaks suggesting its synthesis, while signals from X-ray diffraction (XRD) showed diffraction patterns confirming the synthesis of ZnFe2O4@Chitosan with a crystallite size of 35.14 nm. Scanning electron microscopy (SEM) revealed a homogeneous morphology with a surface area of 12.96 m2 g−1 from the Brunauer–Emmett–Teller (BET) analysis. The vibrating sample magnetometry (VSM) result revealed a saturation magnetization of 2.38 emu g−1. The photodegradation study of CIP, AMP and ERY showed that both photodegradation and adsorption were taking place at the same time with the percentage degradation efficiency in the order CIP (99.80 ± 0.20%) > AMP (94.50 ± 0.10%) > ERY (83.20 ± 0.20%). ZnFe2O4@Chitosan exhibited high stability with capacity > 90% even at the 15th regeneration cycle, suggesting a viable economic value of ZnFe2O4@Chitosan

Visible Light-Driven Photocatalytic Degradation of Ciprofloxacin, Ampicillin and Erythromycin by Zinc Ferrite Immobilized on Chitosan

This study investigated the synthesis of zinc ferrite immobilized on chitosan (ZnFe2O4@Chitosan) and its application in the photodegradation of ciprofloxacin (CIP), ampicillin (AMP) and erythromycin (ERY) in aqueous solution. Results from Fourier transform infrared spectroscopy (FTIR) revealed peaks suggesting its synthesis, while signals from X-ray diffraction (XRD) showed diffraction patterns confirming the synthesis of ZnFe2O4@Chitosan with a crystallite size of 35.14 nm. Scanning electron microscopy (SEM) revealed a homogeneous morphology with a surface area of 12.96 m2 g−1 from the Brunauer–Emmett–Teller (BET) analysis. The vibrating sample magnetometry (VSM) result revealed a saturation magnetization of 2.38 emu g−1. The photodegradation study of CIP, AMP and ERY showed that both photodegradation and adsorption were taking place at the same time with the percentage degradation efficiency in the order CIP (99.80 ± 0.20%) > AMP (94.50 ± 0.10%) > ERY (83.20 ± 0.20%). ZnFe2O4@Chitosan exhibited high stability with capacity > 90% even at the 15th regeneration cycle, suggesting a viable economic value of ZnFe2O4@Chitosan

Copper ferrite immobilized on chitosan: A suitable photocatalyst for the removal of ciprofloxacin, ampicillin and erythromycin in aqueous solution

Copper ferrite (CuFe2O4) was immobilized on chitosan to produce CuFe2O4@Chitosan for the removal of ciprofloxacin (CIP), ampicillin (AMP), and erythromycin (ERY) in water. Characterization of CuFe2O4@Chitosan by X-ray diffraction revealed the crystallite size of 18.12 nm. The Brunauer-Emmett-Teller surface area is 9.95 m2 g−1. The vibrating sample magnetometry revealed a saturation magnetization of 37.69 emu g−1. The degradation efficiency by CuFe2O4@Chitosan towards CIP (94.6 ± 0.50%), AMP (92 ± 1.00%) and ERY (90.30 ± 0.50) presents it as a promising photocatalyst for the removal of antibiotics in aqueous solutions. Regeneration capacity showed CuFe2O4@Chitosan to be a promising photocatalyst for removal of antibiotics in water

Visible Light-Driven Photocatalytic Degradation of Ciprofloxacin, Ampicillin and Erythromycin by Zinc Ferrite Immobilized on Chitosan

Peer reviewed: TrueThis study investigated the synthesis of zinc ferrite immobilized on chitosan (ZnFe2O4@Chitosan) and its application in the photodegradation of ciprofloxacin (CIP), ampicillin (AMP) and erythromycin (ERY) in aqueous solution. Results from Fourier transform infrared spectroscopy (FTIR) revealed peaks suggesting its synthesis, while signals from X-ray diffraction (XRD) showed diffraction patterns confirming the synthesis of ZnFe2O4@Chitosan with a crystallite size of 35.14 nm. Scanning electron microscopy (SEM) revealed a homogeneous morphology with a surface area of 12.96 m2 g−1 from the Brunauer–Emmett–Teller (BET) analysis. The vibrating sample magnetometry (VSM) result revealed a saturation magnetization of 2.38 emu g−1. The photodegradation study of CIP, AMP and ERY showed that both photodegradation and adsorption were taking place at the same time with the percentage degradation efficiency in the order CIP (99.80 ± 0.20%) &gt; AMP (94.50 ± 0.10%) &gt; ERY (83.20 ± 0.20%). ZnFe2O4@Chitosan exhibited high stability with capacity &gt; 90% even at the 15th regeneration cycle, suggesting a viable economic value of ZnFe2O4@Chitosan.</jats:p

Investigation of the Potential of Nebivolol Hydrochloride-Loaded Chitosomal Systems for Tissue Regeneration: In Vitro Characterization and In Vivo Assessment

In this study, we evaluated the synergistic effect of nebivolol hydrochloride (NVH), a third-generation beta-blocker and NO donor drug, and chitosan on the tissue regeneration. Ionic gelation method was selected for the preparation of NVH-loaded chitosomes using chitosan lactate and sodium tripolyphosphate. The effect of different formulation variables was studied using a full factorial design, and NVH entrapment efficiency percentages and particle size were selected as the responses. The chosen system demonstrated high entrapment efficiency (73.68 ± 3.61%), small particle size (404.05 ± 11.2 nm), and good zeta potential value (35.6 ± 0.25 mV). The best-achieved formula demonstrated spherical morphology in transmission electron microscopy and amorphization of the crystalline drug in differential scanning calorimetry and X-ray diffraction. Cell culture studies revealed a significantly higher proliferation of the fibroblasts in comparison with the drug suspensions and the blank formula. An in vivo study was conducted to compare the efficacy of the proposed formula on wound healing. The histopathological examination showed the superiority of NVH-loaded chitosomes on the wound proliferation and the non-significant difference in the collagen deposition after 15 days of the injury to that of intact skin. In conclusion, NVH-loaded chitosomes exhibited promising results in enhancing skin healing and tissue regeneration

Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

In this study, water-soluble chitosan lactate (CL) was reacted with lactobionic acid (LA), a disaccharide with remarkable affinity to hepatic asialoglycoprotein (ASGP) receptors, to form dual liver-targeting LA-modified-CL polymer for site-specific drug delivery to the liver. The synthesized polymer was used to encapsulate baicalin (BA), a promising bioactive flavonoid with pH-dependent solubility, into ultrahigh drug-loaded nanoparticles (NPs) via the ionic gelation method. The successful chemical conjugation of LA with CL was tested and the formulated drug-loaded LA-modified-CL-NPs were assessed in terms of particle size (PS), encapsulation efficiency (EE) and zeta potential (ZP) using full factorial design. The in vivo biodistribution and pharmacokinetics of the designed NPs were assessed using 99mTc-radiolabeled BA following oral administration to mice and results were compared to 99mTc-BA-loaded-LA-free-NPs and 99mTc-BA solution as controls. Results showed that the chemical modification of CL with LA was successfully achieved and the method of preparation of the optimized NPs was very efficient in encapsulating BA into nearly spherical particles with an extremely high EE exceeding 90%. The optimized BA-loaded-LA-modified-CL-NPs showed an average PS of 490 nm, EE of 93.7% and ZP of 48.1 mV. Oral administration of 99mTc-BA-loaded-LA-modified-CL-NPs showed a remarkable increase in BA delivery to the liver over 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA oral solution. The mean area under the curve (AUC0&ndash;24) estimates from liver data were determined to be 11-fold and 26-fold higher from 99mTc-BA-loaded-LA-modified-CL-NPs relative to 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA solution respectively. In conclusion, the outcome of this study highlights the great potential of using LA-modified-CL-NPs for the ultrahigh encapsulation of therapeutic molecules with pH-dependent/poor water-solubility and for targeting the liver

Green Synthesis of Highly Fluorescent Carbon Dots from Bovine Serum Albumin for Linezolid Drug Delivery as Potential Wound Healing Biomaterial: Bio-Synergistic Approach, Antibacterial Activity, and In Vitro and Ex Vivo Evaluation

A simple and green approach was developed to produce novel highly fluorescent bovine serum albumin carbon dots (BCDs) via facile one-step hydrothermal treatment, using bovine serum albumin as a precursor carbon source. Inherent blue photoluminescence of the synthesized BCDs provided a maximum photostability of 90.5 ± 1.2% and was characterized via TEM, FT-IR, XPS, XRD, UV-visible, and zeta potential analyses. By virtue of their extremely small size, intrinsic optical and photoluminescence properties, superior photostability, and useful non-covalent interactions with the synthetic oxazolidinone antibiotic linezolid (LNZ), BCDs were investigated as fluorescent nano-biocarriers for LNZ drug delivery. The release profile of LNZ from the drug delivery system (LNZ–BCDs) revealed a distinct biphasic release, which is beneficial for mollifying the lethal incidents associated with wound infection. The effective wound healing performance of the developed LNZ–BCDs were evaluated through various in vitro and ex vivo assays such as MTT, ex vivo hemolysis, in vitro antibacterial activity, in vitro skin-related enzyme inhibition, and scratch wound healing assays. The examination of LNZ–BCDs as an efficient wound healing biomaterial illustrated excellent biocompatibility and low cytotoxicity against normal human skin fibroblast (HSF) cell line, indicating distinct antibacterial activity against the most common wound infectious pathogens including Staphylococcus aureus (ATCC® 25922) and methicillin-resistant Staphylococcus aureus, robust anti-elastase, anti-collagenase, and anti-tyrosinase activities, and enhanced cell proliferation and migration effect. The obtained results confirmed the feasibility of using the newly designed fluorescent LNZ–BCDs nano-bioconjugate as a unique antibacterial biomaterial for effective wound healing and tissue regeneration. Besides, the greenly synthesized BCDs could be considered as a great potential substitute for toxic nanoparticles in biomedical applications due to their biocompatibility and intense fluorescence characteristics and in pharmaceutical industries as promising drug delivery nano-biocarriers for effective wound healing applications