scholarly journals Preparation of phospholipid-based polycarbonate urethanes for potential applications of blood-contacting implants

2020 ◽  
Vol 7 (5) ◽  
pp. 491-504
Author(s):  
Peichuang Li ◽  
Wanhao Cai ◽  
Xin Li ◽  
Kebing Wang ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Microphase Separation ◽  
Blood Compatibility ◽  
Ex Vivo ◽  
Raw Materials ◽  
Direct Synthesis ◽  
Animal Experiments ◽  
Biological Response ◽  
Superior Performance ◽  
Scanning Calorimetry

Abstract Polyurethanes are widely used in interventional devices due to the excellent physicochemical property. However, non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices. Herein, a novel phospholipid-based polycarbonate urethanes (PCUs) were developed via two-step solution polymerization by direct synthesis based on functional raw materials. Furthermore, PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface. The results of stress–strain curves exhibited excellent tensile properties of PCUs films. Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender, leading to different biological response. In vitro blood compatibility tests including bovine serum albumin adsorption, fibrinogen adsorption and denaturation, platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples. Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability. Finally, animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility. These results high light the strong anti-adhesion property of phospholipid-based PCUs films, which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.

The Development of Pemetrexed Diacid-Loaded Gelatin-Cloisite 30B (MMT) Nanocomposite for Improved Oral Efficacy Against Cancer: Characterization, In-Vitro and Ex-Vivo Assessment

2020 ◽  
Vol 17 (3) ◽  
pp. 246-256
Author(s):  
Kriti Soni ◽  
Ali Mujtaba ◽  
Md. Habban Akhter ◽  
Kanchan Kohli
Keyword(s):  
Drug Release ◽  
Oral Delivery ◽  
Ex Vivo ◽  
Confocal Laser ◽  
Release Mechanism ◽  
Scanning Calorimetry ◽  
Sem Images ◽  
Cloisite 30B ◽  
Ft Ir

Aim: The intention of this investigation was to develop Pemetrexed Diacid (PTX)-loaded gelatine-cloisite 30B (MMT) nanocomposite for the potential oral delivery of PTX and the in vitro, and ex vivo assessment. Background: Gelatin/Cloisite 30 B (MMT) nanocomposites were prepared by blending gelatin with MMT in aqueous solution. Methods: PTX was incorporated into the nanocomposite preparation. The nanocomposites were investigated by Fourier Transmission Infra Red Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM) X-Ray Diffraction (XRD) and Confocal Laser Microscopy (CLSM). FT-IR of nanocomposite showed the disappearance of all major peaks which corroborated the formation of nanocomposites. The nanocomposites were found to have a particle size of 121.9 ± 1.85 nm and zeta potential -12.1 ± 0.63 mV. DSC thermogram of drug loaded nanocomposites indicated peak at 117.165 oC and 205.816 oC, which clearly revealed that the drug has been incorporated into the nanocomposite because of cross-linking of cloisite 30 B and gelatin in the presence of glutaraldehyde. Results: SEM images of gelatin show a network like structure which disappears in the nanocomposite. The kinetics of the drug release was studied in order to ascertain the type of release mechanism. The drug release from nanocomposites was in a controlled manner, followed by first-order kinetics and the drug release mechanism was found to be of Fickian type. Conclusion: Ex vivo gut permeation studies revealed 4 times enhancement in the permeation of drug present in the nanocomposite as compared to plain drug solution and were further affirmed by CLSM. Thus, gelatin/(MMT) nanocomposite could be promising for the oral delivery of PTX in cancer therapy and future prospects for the industrial pharmacy.

Mannosylated Solid Lipid Nanocarriers Of Chrysin To Target Gastric Cancer: Optimization and Cell line Study.

2021 ◽  
Vol 18 ◽  
Author(s):  
Sonia S. Pandey ◽  
Farhinbanu I. Shaikh ◽  
Arti R. Gupta ◽  
Rutvi J. Vaidya
Keyword(s):  
Gastric Cancer ◽  
Particle Size ◽  
Ex Vivo ◽  
Biological Effects ◽  
Entrapment Efficiency ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Solid Lipid ◽  
Lipid Nanocarriers

Background: Despite significant biological effects, the clinical use of chrysin has been restricted because of its poor oral bioavailability. Objective: The purpose of the present research was to investigate the targeting potential of Mannose decorated chrysin (5,7- dihydroxyflavone) loaded solid lipid nanocarrier (MC-SLNs) for gastric cancer. Methods: The Chrysin loaded SLNs (C-SLNs) were developed optimized, characterized and further mannosylated. The C-SLNs were developed with high shear homogenizer, optimized with 32 full factorial designs and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Scanning Electron Microscope (SEM) and evaluated for particle size/polydispersity index, zeta-potential, entrapment efficiency, % release and haemolytic toxicity. The ex-vivo cytotoxicity study was performed on gastric cancer (ACG) and normal cell lines. Results: DSC and XRD data predict the chrysin encapsulation in lipid core and FTIR results confirm the mannosylation of C-SLNs. The optimized C-SLNs exhibited a narrow size distribution with a particle size of 285.65 nm. The % Entrapment Efficiency (%EE) and % controlled release were found to be 74.43% and 64.83%. Once C-SLNs were coated with mannose, profound change was observed in dependent variable - increase in the particle size of MC-SLNs (307.1 nm) was observed with 62.87% release and 70.8% entrapment efficiency. Further, the in vitro studies depicted MC- SLNs to be least hemolytic than pure chrysin and C-SLNs. MC-SLNs were most cytotoxic and were preferably taken up ACG tumor cells as evaluated against C-SLNs. Conclusion: These data suggested that the MC-SLNs demonstrated better biocompatibility and targeting efficiency to treat the gastric cancer.

Pre-Clinical Biocompatibility Testing of Peritoneal Dialysis Solutions

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 5-9 ◽  
Author(s):  
C.J. Holmes
Keyword(s):  
Peritoneal Dialysis ◽  
Screening Program ◽  
Ex Vivo ◽  
Biological Response ◽  
Cell Types ◽  
Hierarchical Level ◽  
Clinical Phase ◽  
Biocompatibility Testing

Pre-clinical biocompatibility testing of peritoneal dialysis (PD) solutions has become an integral part of new solution development. The construction of a pre-clinical screening program for solution biocompatibility should take a hierarchical approach, starting with in vitro cell viability and function assays. The selection of cell types and assay systems for the in vitro studies should be broad enough to permit a balanced interpretation. Whenever possible, animal models are recommended for the next hierarchical level of testing, followed by human ex vivo study designs. Designs of the latter sort provide evidence that a new solution formulation is exerting an altered biological response in vivo; the response is not purely an in vitro artifact or restricted to a given animal species. This article discusses the various approaches available for biocompatibility testing during the pre-clinical phase of solution development, with an emphasis on the advantages and drawbacks of each method.

An Innovative Ex Vivo Vascular Bioreactor as Comprehensive Tool to Study the Behavior of Native Blood Vessels Under Physiologically Relevant Conditions

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Noemi Vanerio ◽  
Marco Stijnen ◽  
Bas A. J. M. de Mol ◽  
Linda M. Kock
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Ultrasound Imaging ◽  
Ex Vivo ◽  
Biological Response ◽  
Vessel Diameter ◽  
Tissue Growth ◽  
In Vivo Models

Abstract Ex vivo systems represent important models to study vascular biology and to test medical devices, combining the advantages of in vitro and in vivo models such as controllability of parameters and the presence of biological response, respectively. The aim of this study was to develop a comprehensive ex vivo vascular bioreactor to long-term culture and study the behavior of native blood vessels under physiologically relevant conditions. The system was designed to allow for physiological mechanical loading in terms of pulsatile hemodynamics, shear stress, and longitudinal prestretch and ultrasound imaging for vessel diameter and morphology evaluation. In this first experience, porcine carotid arteries (n = 4) from slaughterhouse animals were cultured in the platform for 10 days at physiological temperature, CO2 and humidity using medium with blood-mimicking viscosity, components, and stability of composition. As expected, a significant increase in vessel diameter was observed during culture. Flow rate was adjusted according to diameter values to reproduce and maintain physiological shear stress, while pressure was kept physiological. Ultrasound imaging showed that the morphology and structure of cultured arteries were comparable to in vivo. Histological analyses showed preserved endothelium and extracellular matrix and neointimal tissue growth over 10 days of culture. In conclusion, we have developed a comprehensive pulsatile system in which a native blood vessel can be cultured under physiological conditions. The present model represents a significant step toward ex vivo testing of vascular therapies, devices, drug interaction, and as basis for further model developments.

scholarly journals GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 736 ◽  
Author(s):  
Ian J. Villamagna ◽  
Danielle M. McRae ◽  
Aneta Borecki ◽  
Xueli Mei ◽  
François Lagugné-Labarthet ◽  
...  
Keyword(s):  
Side Effects ◽  
Ex Vivo ◽  
Joint Space ◽  
Peroxisome Proliferator ◽  
Scanning Calorimetry ◽  
Peroxisome Proliferator Activated Receptor ◽  
Force Microscopy ◽  
Young’S Moduli ◽  
Joint Disorder

Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor δ (PPARδ) in cartilage may attenuate the development or progression of OA. PPARδ antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt.% drug and had mean diameters of about 600 nm. Differential scanning calorimetry indicated the drug was in crystalline domains in the particles. Atomic force microscopy was used to measure the Young’s moduli of individual particles as 2.8 MPa. In vitro drug release studies showed 11% GSK3787 was released over 30 days. Studies in immature murine articular cartilage (IMAC) cells indicated low toxicity from the drug, empty particles, and drug-loaded particles and that the particles were not taken up by the cells. Ex vivo studies on murine joints showed that the particles could be injected into the joint space and resided there for at least 7 days. Overall, these results indicate that GSK3787-loaded PEA particles warrant further investigation as a delivery system for potential OA therapy.

scholarly journals In-Silico Assisted Development of Supersaturable Preconcentrated Isotropic Mixture of Atazanavir for Augmenting Biopharmaceutical Performance in Presence of H2-Receptor Antagonist

2022 ◽  
Author(s):  
Sheshank Sethi ◽  
Vikas Rana
Keyword(s):  
Receptor Antagonist ◽  
Oral Bioavailability ◽  
In Silico ◽  
Corn Oil ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Superior Performance ◽  
Lymphatic Transport ◽  
H2 Receptor Antagonist

Abstract The therapeutic potential of atazanavir (BCS Class II drug), a highly selective inhibitor of human immunodeficiency virus (HIV-1) has been largely limited due to its low intrinsic solubility at elevated pH resulting in low oral bioavailability. Thus, the current work describes the systematic development, optimization and evaluation of HPMC-AS based supersaturable preconcentrate isotropic mixture (SP-IM) containing long chain triglyceride to improve intestinal lymphatic transport and augment oral bioavailability of atazanavir (ATZ). A D-optimal mixture design was employed for optimization of plain IM containing Corn Oil, Oleic acid, Tween 80 and Propylene Glycol, evaluating CQAs like particle size, PDI, self-emulsification time, % transmittance and drug content. In-silico analysis and in-vitro supersaturation test facilitated the selection of HPMC-AS as a best suited polymeric precipitation inhibitor (PPI) for formulating ATZ loaded SP-IM (ATZ-SP-IM). In-vitro dissolution data indicated that ATZ-SP-IM exhibits superior performance in 0.025N HCl and pH 6.8 over pure drug. Ex-vivo permeation and in-vivo pharmacokinetic study of ATZ-SP-IM corroborated enhanced permeation (2.03 fold) and improved drug absorption via lymphatic transport in wistar rats. Further, the pharmacokinetic performance of ATZ-SP-IM was not affected in presence of H2 receptor antagonist. Therefore, the results showed that ATZ-SP-IM can significantly improve the biopharmaceutical attributes of ATZ so as to lay a foundation of further research on the new dosage form of ATZ.

scholarly journals Formulation, Preparation, Characterization, and Evaluation of Dicarboxylic Ionic Liquid Donepezil Transdermal Patches

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 205
Author(s):  
Linh Dinh ◽  
Soohun Lee ◽  
Sharif Md Abuzar ◽  
Heejun Park ◽  
Sung-Joo Hwang
Keyword(s):  
Ionic Liquid ◽  
Ex Vivo ◽  
Optical Microscope ◽  
Skin Permeability ◽  
Resonance Spectroscopy ◽  
Scanning Calorimetry ◽  
Ionic Bonds ◽  
Gastrointestinal Side Effects ◽  
Permeability Studies

Donepezil (DPZ) is generally administered orally to treat Alzheimer’s disease (AD). However, oral administration can cause gastrointestinal side effects. Therefore, to enhance compliance, a new way to deliver DPZ from transdermal patch was developed. Ionic bonds were created by dissolving dicarboxylic acid and DPZ in ethanol, resulting in a stable ionic liquid (IL) state. The synthesized ILs were characterized by differential scanning calorimetry, optical microscope, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The DPZ ILs were then transformed to a suitable drug-in-adhesive patch for transdermal delivery of DPZ. The novel DPZ ILs patch inhibits crystallization of the IL, indicating coherent design. Moreover, DPZ ILs and DPZ IL patch formulations performed excellent skin permeability compared to that of the DPZ free-base patch in both in vitro and ex vivo skin permeability studies.

Fast Dissolving Sublingual Strips: A Novel Approach for the Delivery of Isosorbide Dinitrate

2019 ◽  
Vol 25 (4) ◽  
pp. 311-318
Author(s):  
Marzieh Fathei ◽  
Mitra Alami-milani ◽  
Sara Salatin ◽  
Sharahm Sattari ◽  
Hassan Montazam ◽  
...  
Keyword(s):  
Drug Release ◽  
Isosorbide Dinitrate ◽  
Moisture Absorption ◽  
Ex Vivo ◽  
Hydroxypropyl Methylcellulose ◽  
Drug Bioavailability ◽  
Scanning Calorimetry ◽  
Surface Ph ◽  
Drug Content

Background: Isosorbide dinitrate (ISDN) is used for treating the angina attacks. In addition, oral ISDN is available in immediate and sustained release formulations and the bioavailability of ISDN is about 20-25% when taken orally. Further, the ISDN films are developed for sublingual drug delivery by improving drug bioavailability. The present study aimed to design and evaluate the physicochemical properties of the film formulation for sublingual delivery of ISDN. Methods: In the present study, sublingual films were prepared by the solvent casting technique using the hydroxypropyl methylcellulose (HPMC) polymers (i.e., 100, 150 and 200 mg) with a different drug to polymer ratios (i.e., 1:5, 1:7.5 and 1:10). Then, ISDN was evaluated for the film appearance, drug content, surface pH, mucoadhesion force, differential scanning calorimetry (DSC), in vitro drug release, and ex vivo permeability. Results: Based on the results, F3 formulation (1:10 ISDN to HPMC ratio) showed acceptable thickness (0.93 mm), weight (11.14 mg), surface pH (7.82), moisture absorption capacity (6.08%), elasticity (>200), mucoadhesion force (18.05 N/cm2), and drug content (6.22%). Furthermore, the results demonstrated that HPMC polymer improved the characteristics of the films, modified the bioadhesiveness, and finally, enhanced elasticity. However, DSC thermogram failed to show any crystalline drug substance in the films except for F1 (immediate release) and the endothermic peak of ISDN was absent in F2 and F3 films. Therefore, the drug which was entrapped into the film was in an amorphous or disturbed-crystalline phase of the molecular dispersion or dissolved in the melted polymer in the polymeric matrix. Moreover, the drug release from the films was faster compared to the tablet® (P<0.05). Conclusion: In general, the formulation of F1 was observed to be an appropriate candidate for developing the sublingual film for the remedial use.

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