scholarly journals Acousticofluidics For Diagnostics And Intracellular Delivery

2021 ◽  
Author(s):  
Alinaghi Salari
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Microfluidic Device ◽  
Acoustic Waves ◽  
Microfluidic Channel ◽  
Intracellular Delivery ◽  
Cell Stiffness ◽  
Design Parameters ◽  
In Vitro Tests

<div>In biomedical research, there is a high demand for tools that provide high precision, costeffective, and portable methodologies for diagnostic and drug delivery purposes. The main focus of this thesis is on ultrasound techniques, where sound waves are employed for conducting in vivo and in vitro tests for different diagnostic and therapeutic applications. First, bubble-mediated ultrasound approaches for imaging are explored, and then, a bubble-free acoustofluidic strategy is proposed for in vitro intracellular delivery applications. </div><div>As a significant component of many ultrasound techniques, microbubbles have been used as contrast agents and for targeted imaging and drug delivery applications. Size, monodispersity, and stability of microbubbles are important characteristics for the effectiveness of these techniques, and therefore, various methods have been developed for producing microbubbles. In the first microfluidic approach, an expansion-mediated breakup regime is proposed that enables a controlled breakup of large bubbles into smaller size microbubbles in a microfluidic device. Also, various population distributions are reported, and the governing dimensionless numbers are identified. In the second approach, by taking advantage of the dynamics of the bubble size variation inside a gas permeable microfluidic device, the shrinkage of large bubbles into smaller size microbubbles is presented. Theoretical modeling and experimental verification are conducted to identify the design parameters governing the final size of the microbubbles. It is also shown that by controlling the mixing ratio of a high-molecular-weight gas with a low-molecular-weight gas, this approach could enable the production of nanobubbles.<br></div><div>An acoustofluidic strategy for probing cellular stiffness and facilitating intracellular delivery is also presented. Acoustic waves are employed to control the oscillations of adherent cells in a microfluidic channel. Novel observations are reported that individual cells are able to induce microstreaming flow when they are excited by controlled acoustic waves in vitro. A strong correlation between cell stiffness and cell-induced microstreaming flow is observed. Also, it is shown that the combined effect of acoustic excitation and cell-induced microstreaming can facilitate the cellular uptake of different size cargo materials. Successful delivery of 500 kDa dextran to various cell lines with unprecedented efficiency in the range of 65–85% in a 20 min treatment is demonstrated.<br></div>

scholarly journals Acousticofluidics For Diagnostics And Intracellular Delivery

2021 ◽  
Author(s):  
Alinaghi Salari
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Microfluidic Device ◽  
Acoustic Waves ◽  
Microfluidic Channel ◽  
Intracellular Delivery ◽  
Cell Stiffness ◽  
Design Parameters ◽  
In Vitro Tests

<div>In biomedical research, there is a high demand for tools that provide high precision, costeffective, and portable methodologies for diagnostic and drug delivery purposes. The main focus of this thesis is on ultrasound techniques, where sound waves are employed for conducting in vivo and in vitro tests for different diagnostic and therapeutic applications. First, bubble-mediated ultrasound approaches for imaging are explored, and then, a bubble-free acoustofluidic strategy is proposed for in vitro intracellular delivery applications. </div><div>As a significant component of many ultrasound techniques, microbubbles have been used as contrast agents and for targeted imaging and drug delivery applications. Size, monodispersity, and stability of microbubbles are important characteristics for the effectiveness of these techniques, and therefore, various methods have been developed for producing microbubbles. In the first microfluidic approach, an expansion-mediated breakup regime is proposed that enables a controlled breakup of large bubbles into smaller size microbubbles in a microfluidic device. Also, various population distributions are reported, and the governing dimensionless numbers are identified. In the second approach, by taking advantage of the dynamics of the bubble size variation inside a gas permeable microfluidic device, the shrinkage of large bubbles into smaller size microbubbles is presented. Theoretical modeling and experimental verification are conducted to identify the design parameters governing the final size of the microbubbles. It is also shown that by controlling the mixing ratio of a high-molecular-weight gas with a low-molecular-weight gas, this approach could enable the production of nanobubbles.<br></div><div>An acoustofluidic strategy for probing cellular stiffness and facilitating intracellular delivery is also presented. Acoustic waves are employed to control the oscillations of adherent cells in a microfluidic channel. Novel observations are reported that individual cells are able to induce microstreaming flow when they are excited by controlled acoustic waves in vitro. A strong correlation between cell stiffness and cell-induced microstreaming flow is observed. Also, it is shown that the combined effect of acoustic excitation and cell-induced microstreaming can facilitate the cellular uptake of different size cargo materials. Successful delivery of 500 kDa dextran to various cell lines with unprecedented efficiency in the range of 65–85% in a 20 min treatment is demonstrated.<br></div>

scholarly journals Comparative Studies on the Anticoagulant Profile of Branded Enoxaparin and a New Biosimilar Version

2020 ◽  
Vol 26 ◽  
pp. 107602962096082
Author(s):  
Dalia Qneibi ◽  
Eduardo Ramacciotti ◽  
Ariane Scarlatelli Macedo ◽  
Roberto Augusto Caffaro ◽  
Leandro Barile Agati ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Performance ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Factor Xa ◽  
In Vivo Studies ◽  
In Vitro Tests ◽  
Thrombin Time

Low molecular weight heparins (LMWH) represent depolymerized heparin prepared by various methods that exhibit differential, biochemical and pharmacological profiles. Enoxaparin is prepared by benzylation followed by alkaline depolymerization of porcine heparin. Upon the expiration of its patent, several biosimilar versions of enoxaparin have become available. Heparinox (Sodic enoxaparine; Cristália Produtos Químicos Farmacêuticos LTDA, Sao Paulo, Brazil) is a new biosimilar form of enoxaparin. We assessed the molecular weight and the biochemical profile of Heparinox and compared its properties to the original branded enoxaparin (Lovenox; Sanofi, Paris, France). Clotting profiles compared included activated clotting time, activated partial thromboplastin time (aPTT), and thrombin time (TT). Anti-protease assays included anti-factor Xa and anti-factor IIa activities. Thrombin generation was measured using a calibrated automated thrombogram and thrombokinetic profile included peak thrombin, lag time and area under the curve. USP potency was determined using commercially available assay kits. Molecular weight profiling was determined using high performance liquid chromatography. We determined that Heparinox and Lovenox were comparable in their molecular weight profile. Th anticoagulant profile of the branded and biosimilar version were also similar in the clot based aPTT and TT. Similarly, the anti-Xa and anti-IIa activities were comparable in the products. No differences were noted in the thrombin generation inhibitory profile of the branded and biosimilar versions of enoxaparin. Our studies suggest that Heparinox is bioequivalent to the original branded enoxaparin based upon in vitro tests however will require further in vivo studies in animal models and humans to determine their clinical bioequivalence.

scholarly journals Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 365 ◽  
Author(s):  
Heejun Park ◽  
Eun-Sol Ha ◽  
Min-Soo Kim
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Drug Application ◽  
In Vitro Digestion ◽  
Delivery Systems ◽  
Water Soluble ◽  
Current Status ◽  
In Vitro Tests

Self-emulsifying drug delivery systems (SEDDSs) are a vital strategy to enhance the bioavailability (BA) of formulations of poorly water-soluble compounds. However, these formulations have certain limitations, including in vivo drug precipitation, poor in vitro in vivo correlation due to a lack of predictive in vitro tests, issues in handling of liquid formulation, and physico-chemical instability of drug and/or vehicle components. To overcome these limitations, which restrict the potential usage of such systems, the supersaturable SEDDSs (su-SEDDSs) have gained attention based on the fact that the inclusion of precipitation inhibitors (PIs) within SEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This improves the BA of drugs and reduces the variability of exposure. In addition, the formulation of solid su-SEDDSs has helped to overcome disadvantages of liquid or capsule dosage form. This review article discusses, in detail, the current status of su-SEDDSs that overcome the limitations of conventional SEDDSs. It discusses the definition and range of su-SEDDSs, the principle mechanisms underlying precipitation inhibition and enhanced in vivo absorption, drug application cases, biorelevance in vitro digestion models, and the development of liquid su-SEDDSs to solid dosage forms. This review also describes the effects of various physiological factors and the potential interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SEDDSs. In particular, several considerations relating to the properties of PIs are discussed from various perspectives.

Lipid Membranes: Biological Inspiration for Micro and Nano Encapsulation Technologies, Especially Drug Delivery

2003 ◽  
Vol 774 ◽  
Author(s):  
David Needham
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Solid Tumors ◽  
Tumor Regression ◽  
Unmet Need ◽  
Lipid Vesicles ◽  
Design Parameters ◽  
Material System ◽  
Lipid Bilayer Membranes

AbstractOur approach to biologically inspired materials and materials systems recognizes biology (at all scale levels) as a series of products that fulfill particular functions. It then links material composition and structure to function through properties and therefore attempts to bring mechanism to processes and functions of biology. As an example of this approach we have focused on the lipid bilayer membranes of blood cells, like erythrocytes and neutrophils, as a bioinspired material system for drug delivery leading to the creation of waxy, nano capsules called liposomes that can be triggered to release their drug by hyperthermia. Thus, while Nature's encapsulation technology provides the inspiration, the mechanism of drug release is non-natural. The necessary design parameters for the required functions of drug encapsulation, i.e. drug retention, circulation half life, and eventual thermally-triggered drug release, were obtained through extensive experimentation and modeling of artificial lipid vesicles by us and others, with much of the mechanical and thermomechanical properties, molecular exchange, and in vitro performance investigated by a direct micropipet manipulation technique. With respect to cancer chemotherapy, the unmet need for primary solid tumors is to deliver more drug to the tumor tissue thereby reducing the tumor size (debulking) while at the same time reducing toxic side effects. It is with these criteria in mind that we developed the temperature-triggered liposome for the treatment of solid tumors. This paper then, describes this liposome development and its performance in vivo, where, in some cases, the temperature-triggered release of drug directly in the blood stream and tumor resulted in complete tumor regression. What this example also shows is that through material property measurement and modeling, new insights into Nature's functions and designs can be discovered in a reverse engineering process from which new products can then be forward engineered to solve engineering and product problems in health, technology, and the environment.

scholarly journals In Vitro Tests of FDM 3D-Printed Diclofenac Sodium-Containing Implants

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5889
Author(s):  
Petra Arany ◽  
Ildikó Papp ◽  
Marianna Zichar ◽  
Máté Csontos ◽  
János Elek ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Fused Deposition Modeling ◽  
Delivery Systems ◽  
In Vitro Tests ◽  
Fused Deposition ◽  
Deposition Modeling ◽  
3D Printed ◽  
Implantable Drug Delivery Systems

One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and biocompatibility investigations. Our objective was to manufacture implantable drug delivery systems using fused deposition modeling, and in vitro tests were performed for the assessment of these products. Polylactic acid, antibacterial polylactic acid, polyethylene terephthalate glycol, and poly(methyl methacrylate) filaments were selected, and samples with 16, 19, or 22 mm diameters and 0%, 5%, 10%, or 15% infill percentages were produced. The dissolution test was performed by a USP dissolution apparatus 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye (MTT)-based prolonged cytotoxicity test was performed on Caco-2 cells to certify the cytocompatibility properties. The implantable drug delivery systems were characterized by thermogravimetric and heatflow assay, contact angle measurement, scanning electron microscopy, microcomputed tomography, and Raman spectroscopy. Based on our results, it can be stated that the samples are considered nontoxic. The dissolution profiles are influenced by the material properties of the polymers, the diameter, and the infill percentage. Our results confirm the potential of fused deposition modeling (FDM) 3D printing for the manufacturing of different implantable drug delivery systems in personalized medicine and may be applied during surgical interventions.

scholarly journals A Comparative Study of the Effects of Heparin and a Low Molecular Weight Semi-Synthetic Heparin Analogue Upon Platelet Function

1977 ◽  
Author(s):  
R. Michalski ◽  
D. A. Lane ◽  
V. V. Kakkar
Keyword(s):  
Molecular Weight ◽  
Intravenous Injection ◽  
Platelet Function ◽  
Factor Xa ◽  
In Vitro Tests ◽  
Low Molecular Weight ◽  
Clotting Time ◽  
Induced Aggregation

We have already reported O) some in vitro and in vivo properties of a low molecular weight glycosaminoglycan polysulphate. It was found that while this semi-synthetic heparin analogue (SSHA) was virtually inactive in a number of in vitro clotting assays, following intravenous or subcutaneous injection it has a more specific anti-Xa potentiating effect than heparin. In the present communication a comparison has been made of some effects of SSHA and heparin upon platelet function. In several of the in vitro tests performed, such as their potentiating effect on ADP and adrenaline induced aggregation and their effects on the aggregation of washed platelets by Factor Xa, heparin proved to be far more potent than SSHA. It was found that after intravenous injection of both drugs, PRP samples containing comparable anti-Factor Xa activities responded differently to the addition of thrombin as SSHA barely inhibited thrombin induced aggregation. Similarly, SSHA had little effect on the dilute thrombin clotting time of plasma, following intravenous injection. Heparin and analogue were neutralised to approximately the same degree by a crude PF4 preparation, and similar transient thrombocytopenia effects were observed with both drugs.

scholarly journals Synthesis and Properties of Low-Molecular-Weight PEI-Based Lipopolymers for Delivery of DNA

Polymers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1060 ◽  
Author(s):  
Miao-Miao Xun ◽  
Zheng Huang ◽  
Ya-Ping Xiao ◽  
Yan-Hong Liu ◽  
Ji Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Transfection Efficiency ◽  
Dna Delivery ◽  
Low Molecular Weight ◽  
Zeta Potentials ◽  
Poor Efficacy ◽  
Mcf 7

Rapid enzymatic degradation and fragmentation during DNA administration can result in limited gene expression, and consequently, poor efficacy. It is necessary to use novel vectors for DNA delivery. Herein, we aimed to design useful carriers for enhancing transfection efficiency (TE). These lipopolymers were prepared through Michael addition reactions from low-molecular-weight (LMW) polyethyleneimine (PEI) and linkers with three kinds of steroids. Agarose gel electrophoresis assay results displayed that the three lipopolymers could condense plasmid DNA well, and the formed polyplexes had appropriate sizes around 200–300 nm, and zeta potentials of about +25–40 mV. The results of in vitro experiments using HeLa, HEK293, and MCF-7 cells showed that these lipopolymers present higher TE than 25-kDa PEI, both in the absence and presence of 10% serum. Flow cytometry and confocal microscopy studies also demonstrated that these lipopolymer/DNA complexes present higher cellular uptake and intracellular distribution. The measurement of critical micelle concentration (CMC) revealed that these lipopolymers could form micelles, which are suited for drug delivery. All results suggest that the three materials may serve as hopeful candidates for gene and drug delivery in future in vivo applications.

scholarly journals Polylactic Acid and Polycaprolactone Blended Cosmetic Microneedle for Transdermal Hispidin Delivery System

2021 ◽  
Vol 11 (6) ◽  
pp. 2774
Author(s):  
Seungyeon Lee ◽  
Jihye Lee ◽  
Kanghyun Choi ◽  
Hyoseon Kim ◽  
Youngkum Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Polylactic Acid ◽  
Skin Permeability ◽  
In Vitro Tests ◽  
Dependent Manner ◽  
Skin Cells ◽  
Skin Cell ◽  
Polymeric Blends ◽  
Anti Inflammatory

Microneedles (MNs) are a new system of effective drug delivery that create micron-sized pathways to the epidermis or upper dermis regions of the skin. In this study, we developed coated-type microneedles for direct hispidin delivery to the skin. Hispidin is a well-known plant-derived antioxidant component showing antitumor, anti-inflammatory, antiallergic, antiangiogenic, antioxidant, hypoglycemic, hypolipidemic, and immunomodulatory activities. Polymeric blends of polylactic acid (PLA) and polycaprolactone (PCL) were casted as MNs to enhance skin permeability. PLA/PCL MNs exhibited the highest strength of 51.26 MPa with a width of ~200 ųm. Hispidin was directly coated onto the MNs with PLA/PCL blends to form delivery layers. Compared to the hispidin-only delivery layer, skin permeability of hispidin increased by over 50% when using agarose gel in in vitro tests. In a dose-dependent manner, hispidin coated on PLA/PCL MNs also showed a brightening effect, as well as anti-inflammatory activity at the gene and protein level in skin cell culture experiments. It also demonstrated antimicrobial activity, and showed no cytotoxicity to skin cells. These results suggest that the PLA/PCL MN system with hispidin may have great potential as a prototype platform for various drug delivery systems, allowing the development of more effective subcutaneous delivery of vaccines, oligonucleotides, insulin, and many other cosmetic applications.

The Influence of Fumaric Anhydride on Bioadhesive Polymer Compositions

1998 ◽  
Vol 550 ◽  
Author(s):  
C.A. Santos ◽  
B.D. Freedman ◽  
S. Ghosn ◽  
E. Mathiowitz
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Fumaric Acid ◽  
Intestinal Lumen ◽  
Low Molecular Weight ◽  
Molar Ratios ◽  
Work Measurement ◽  
Bioadhesive Polymers

AbstractBioadhesive polymers are useful as drug delivery systems designed to adhere to the gastrointestinal lumen. The interaction between polymer and mucosal tissue influences residence time of the polymeric device and greatly affects the bioavailability of encapsulated drug. Poly(fumaric-co-sebacic anhydride) [P(FA:SA)] demonstrated impressive results in a variety of in vitro and in vivo experiments designed to test bioadhesion of microspheres. Among different molar ratios of P(FA:SA), adhesive measurements increased with increasing fumaric acid (FA) content. Using a modified microbalance technique, P(FA:SA)10:90 yielded a tensile work measurement of 82.99±12.76 nJ (mean±SEM) while that for P(FA:SA)70:30 was 453.23±47.73 nJ. A low molecular weight substance, fumaric anhydride prepolymer (FAPP), the oligomer form of fumaric acid, was incorporated into the microspheres and greatly increased the bioadhesive properties of P(FA:SA) as well as those of the relatively non-bioadhesive polymer poly(caprolactone) (PCL). Tensile work of P(FA:SA)20:80 was 32.95±5.42 nJ, and P(FA:SA)20:80 with 25% FAPP yielded a tensile work measurement of 556.28±113.12 nJ. Adhesion testing with PCL yielded a tensile work measurement of 7.93±1.84 nJ, while that for PCL with 25% FAPP was 1629.54±307.55 nJ. The effect of FA on drug delivery was evaluated in vitro using the P(FA:SA):FAPP blend with the everted intestinal sac technique. A low molecular weight drug (sodium salicylate) encapsulated in P(FA:SA)20:80 passed through the everted intestinal lumen to the interior of the sac to yield a concentration of 11.17±0.93 mg/dL, and drug encapsulated in P(FA:SA)20:80 with 10% FAPP yielded a concentration of 16.25±1.68 mg/dL (P<0.05). Unencapsulated drug passed through the intestinal lumen to yield a concentration of 8.09±-0.36 mg/dL. These experiments demonstrate that fumaric anhydride could be a very important component in bioadhesive polymer systems.

scholarly journals A COMPREHENSIVE REVIEW ON SUPERSATURABLE SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM

2021 ◽  
pp. 40-44
Author(s):  
MUTHADI RADHIKA REDDY ◽  
KUMAR SHIVA GUBBIYAPPA
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
In Vitro Tests ◽  
Drug Bioavailability ◽  
Advantages And Disadvantages ◽  
Anti Cancer

Lipid-based drug delivery systems are extensively reported in the literature for enhancing drug solubility, permeability, and bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) are a superior strategy for enhancing solubility and bioavailability of poorly water-soluble compounds and the most prevailing and commercially viable oil-based approach for drugs that exhibit low dissolution rate and inadequate absorption. However, these formulations have few limitations that include in vivo drug precipitation, inferior in vitro in vivo correlation owing to unavailability of in vitro tests, handling issues of liquid formulation, and physicochemical instability of drugs. These limitations are overcome by potential systems such as supersaturable SNEDDS (S-SNEDDS) which are prepared by addition of precipitation inhibitors into formulated SNEDDS to maintain drug supersaturation post dispersion in gastrointestinal tract. These systems improve drug bioavailability and reduce the inconsistency of exposure. In addition, these formulations also help to overcome the drawbacks of liquid and capsule dosage forms. The S-SNEDDS provides an effective approach for improving the dissolution and bioavailability of anti-cancer agents. In this article, an attempt was made to present an overview of SNEDDS, S-SNEDDS, their mechanism, formulation excipients, recent advancements, advantages, and disadvantages of SNEDDS formulations. The article also focuses on reviewing the application of S-SNEDDS in enhancing the solubility and bioavailability of anti-cancer drugs in cancer therapy.

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