Versatile membrane-based microfluidic platform for in vitro drug diffusion testing mimicking in vivo environments

2021 ◽  
pp. 102462
Author(s):  
O. Mitxelena-Iribarren ◽  
C. Olaizola ◽  
S. Arana ◽  
M. Mujika
Keyword(s):  
Microfluidic Platform ◽  
Drug Diffusion

scholarly journals A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Neda Dadgar ◽  
Alan M. Gonzalez-Suarez ◽  
Pouria Fattahi ◽  
Xiaonan Hou ◽  
John S. Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Drug Testing ◽  
Microfluidic Devices ◽  
Needle Aspiration ◽  
High Concentration ◽  
Microfluidic Platform ◽  
Drug Concentrations

Abstract There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer. Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants. However, standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process. Other limitations include variability in the ability to successfully establish a stable line and inconsistency in the dimensions of these microcancers for in vivo drug response measurements. This paper explored the utility of microfluidics in the cultivation of cancer cell spheroids. Six patient-derived xenograft (PDX) tumors of high-grade serous ovarian cancer were used as the source material to demonstrate that viability and epithelial marker expression in the microfluidic cultures was superior to that of Matrigel or large volume 3D cultures. To further demonstrate the potential for miniaturization and multiplexing, we fabricated multichamber microfluidic devices with integrated microvalves to enable serial seeding of several chambers followed by parallel testing of several drug concentrations. These valve-enabled microfluidic devices permitted the formation of spheroids and testing of seven drug concentrations with as few as 100,000 cancer cells per device. Overall, we demonstrate the feasibility of maintaining difficul-to-culture primary cancer cells and testing drugs in a microfluidic device. This microfluidic platform may be ideal for drug testing and personalized therapy when tumor material is limited, such as following the acquisition of biopsy specimens obtained by fine-needle aspiration.

Fractal Analysis of Tissue Biocompatible Neuroreservoir

2009 ◽  
Vol 15 ◽  
pp. 121-126 ◽  
Author(s):  
T. López ◽  
M. Patiño-Ortiz ◽  
Alexander S. Balankin ◽  
Richard D. González
Keyword(s):  
Pore Space ◽  
Sol Gel ◽  
Water Concentration ◽  
Fractal Dimensions ◽  
Electronic Microscopy ◽  
Drug Diffusion ◽  
The Matrix ◽  
Nanostructured Titania

Sol-gel nanostructured titania (TiO2) was functionalized in order to produce a nanomaterial biocompatible with brain tissue. Neuroreservoirs made from titania microtubes have been used to release sodium phenytoin and valproic acid. In vitro and in vivo probes were used to treat the epilepsy disease. Pore space topology and interactions between matrix and drug are the most important phenomena that affect the drug diffusion and liberation kinetics. Accordingly, fractal morphology of nanostructured titania as a function of pH and polarity of the drug added during the gelation reactions was studied. The transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), and N2 adsorption (BET) were employed to characterize the nanomaterials with maximum amount of air hollows occluded inside a drug. It was found that the clusters and pores in nanostructured titania are characterized by the universal fractal dimensions and . However, the characteristic sizes of particles and pores, the porosity, and the fractal dimension of pore surface ( ) are dependent on hydrolysis water concentration added during the gelation reaction. So, the matrix hydroxylation permits to control the drug liberation kinetics.

scholarly journals Formulation development and Stability Studies of Meropenem Extended-Release matrix Tablets

2018 ◽  
pp. 1-12
Author(s):  
Mohini Sihare ◽  
Rajendra Chouksey
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Methyl Cellulose ◽  
Film Coating ◽  
Matrix Tablets ◽  
Formulation Development ◽  
High Concentration ◽  
Drug Diffusion

The aim of this research was to develop a new hydrophilic matrix system containing meropenem (MEX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxyl propyl methyl cellulose or poly (ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at 40 ± 2°C and 75± 5% relative humidity), and the film-coating process is recommended to avoid MEX photo-degradation. The dissolution profiles demonstrated an extended-release of MEX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo.

scholarly journals Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Paulo Renato Oliveira ◽  
Cassiana Mendes ◽  
Lilian Klein ◽  
Maximiliano da Silva Sangoi ◽  
Larissa Sakis Bernardi ◽  
...  
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Film Coating ◽  
Matrix Tablets ◽  
Formulation Development ◽  
High Concentration ◽  
Drug Diffusion ◽  
Erosion Mechanisms

The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at40±2°C and75±5% relative humidity), and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo.

scholarly journals Hydrogel-based platforms to mimic in vivo drug diffusion: A multicenter research

2020 ◽  
Author(s):  
Paola Petrini ◽  
Daniela Pacheco ◽  
Francesco Briatico Vangosa ◽  
Cosmin S. Butnarasu ◽  
Livia Visai ◽  
...  
Keyword(s):  
High Throughput ◽  
Screening Tool ◽  
In Vitro Screening ◽  
High Throughput Analysis ◽  
Throughput Analysis ◽  
Drug Diffusion ◽  
Preclinical Trials ◽  
State Of Art

An airway mucus model is proposed thus serving as an in vitro screening tool with the aim to reduce the number of noneffective drugs reaching the preclinical trials. The engineered mucus model is an easy-to-use and easy-to-produce tool that can be easily coupled to state-of-art diffusion models and it is compatible with high throughput analysis. This platform will serve as the basis to implement the complexity of the model in terms of components, also including the effect of bacteria

Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

1982 ◽  
Vol 40 ◽  
pp. 142-145
Author(s):  
E. J. Kollar
Keyword(s):  
Connective Tissue ◽  
Oral Mucosa ◽  
Basal Lamina ◽  
Functional Derivatives ◽  
Specific Source ◽  
Dental Epithelium ◽  
Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

Ultrastructure of melanocyte-keratinocyte interactions and pigment transfer in vitro

1978 ◽  
Vol 36 (2) ◽  
pp. 650-651
Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo
Keyword(s):  
Direct Injection ◽  
Skin Pigmentation ◽  
Freeze Fracture ◽  
Pigment Granule ◽  
Time Lapse ◽  
Ultrastructural Level ◽  
Lanthanum Tracer ◽  
A Cell

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Probing the ultrastructure of the mitotic and meiotic spindle in eggs: An expeditious approach based on semi-thin (0.25 μm) serial sections

1983 ◽  
Vol 41 ◽  
pp. 552-555
Author(s):  
Conly L. Rieder ◽  
S. Bowser ◽  
R. Nowogrodzki ◽  
K. Ross ◽  
G. Sluder
Keyword(s):  
Small Sample Size ◽  
Small Sample ◽  
Meiotic Spindle ◽  
Serial Sections ◽  
Mitotic Apparatus ◽  
Thin Sections ◽  
Cell Cycles ◽  
Ultrastructural Studies

Eggs have long been a favorite material for studying the mechanism of karyokinesis in-vivo and in-vitro. They can be obtained in great numbers and, when fertilized, divide synchronously over many cell cycles. However, they are not considered to be a practical system for ultrastructural studies on the mitotic apparatus (MA) for several reasons, the most obvious of which is that sectioning them is a formidable task: over 1000 ultra-thin sections need to be cut from a single 80-100 μm diameter egg and of these sections only a small percentage will contain the area or structure of interest. Thus it is difficult and time consuming to obtain reliable ultrastructural data concerning the MA of eggs; and when it is obtained it is necessarily based on a small sample size.We have recently developed a procedure which will facilitate many studies concerned with the ultrastructure of the MA in eggs. It is based on the availability of biological HVEM's and on the observation that 0.25 μm thick serial sections can be screened at high resolution for content (after mounting on slot grids and staining with uranyl and lead) by phase contrast light microscopy (LM; Figs 1-2).

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