Dependence of perpendicular pressure to luminal surface on heating drug delivery performance using a laser-mediated thermal balloon with porcine carotid artery walls ex vivo

Background and Objectives: To develop electro-sensitive transdermal drug delivery systems (ETDDS) using polyacrylamide-grafted-pectin (PAAm-g-PCT) copolymer hydrogel for rivastigmine delivery. Methods: Free radical polymerization and alkaline hydrolysis technique was employed to synthesize PAAm-g-PCT copolymer hydrogel. The PAAm-g-PCT copolymeric hydrogel was used as a reservoir and cross-linked blend films of PCT and poly(vinyl alcohol) as rate-controlling membranes (RCMs) to prepare ETDDS. Results: The pH of the hydrogel reservoir was found to be in the range of 6.81 to 6.93 and drug content was 89.05 to 96.29%. The thickness of RCMs was in the range of 51 to 99 μ and RCMs showed permeability behavior against water vapors. There was a reduction in the water vapor transmission rate as the glutaraldehyde (GA) concentration was increased. The drug permeation rate from the ETDDS was enhanced under the influence of electric stimulus against the absence of an electric stimulus. The increase in flux by 1.5 fold was recorded with applied electric stimulus. The reduction in drug permeability observed when the concentration of GA was increased. Whereas, the permeability of the drug was augmented as an electric current was changed from 2 to 8 mA. The pulsatile drug release under “on– off” cycle of electric stimulus witnessed a faster drug release under ‘on’ condition and it was slow under ‘off’ condition. The alteration in skin composition after electrical stimulation was confirmed through histopathology studies. Conclusion: The PAAm-g-PCT copolymer hydrogel is a useful carrier for transdermal drug delivery activated by an electric signal to provide on-demand release of rivastigmine.

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Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro/Ex Vivo Studies

Pharmaceutics ◽

10.3390/pharmaceutics12060544 ◽

2020 ◽

Vol 12 (6) ◽

pp. 544

Author(s):

Miao Wang ◽

Sung-Kyun You ◽

Hong-Ki Lee ◽

Min-Gu Han ◽

Hyeon-Min Lee ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Anticancer Agents ◽

Lipid Membrane ◽

Ex Vivo ◽

System Optimization ◽

Raw Material ◽

Phospholipid Complex ◽

Low Solubility

Docetaxel (DTX) has clinical efficacy in the treatment of breast cancer, but it is difficult to develop a product for oral administration, due to low solubility and permeability. This study focused on preparing a self-microemulsifying drug delivery system (SME) loaded with DTX-phospholipid complex (DTX@PLC), to improve the dissolution and gastrointestinal (GI) permeability of DTX. A dual technique combining the phospholipid complexation and SME formulation described as improving upon the disadvantages of DTX has been proposed. We hypothesized that the complexation of DTX with phospholipids can improve the lipophilicity of DTX, thereby increasing the affinity of the drug to the cell lipid membrane, and simultaneously improving permeability through the GI barrier. Meanwhile, DTX@PLC-loaded SME (DTX@PLC-SME) increases the dissolution and surface area of DTX by forming a microemulsion in the intestinal fluid, providing sufficient opportunity for the drug to contact the GI membrane. First, we prepared DTX@PLC-SME by combining dual technologies, which are advantages for oral absorption. Next, we optimized DTX@PLC-SME with nanosized droplets (117.1 nm), low precipitation (8.9%), and high solubility (33.0 mg/g), which formed a homogeneous microemulsion in the aqueous phase. Dissolution and cellular uptake studies demonstrated that DTX@PLC-SME showed 5.6-fold higher dissolution and 2.3-fold higher DTX uptake in Caco-2 cells than raw material. In addition, an ex vivo gut sac study confirmed that DTX@PLC-SME improved GI permeability of DTX by 2.6-fold compared to raw material. These results suggested that DTX@PLC-SME can significantly overcome the disadvantages of anticancer agents, such as low solubility and permeability.

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Triple Drug Fixed Dose Combination Metered Dose Inhaler With Stable And Equivalent Drug Delivery Performance Relative To Individual And Dual Subcomponents

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a3966 ◽

2012 ◽

Cited By ~ 1

Author(s):

David Lechuga-Ballesteros ◽

Reinhard Vehring ◽

Vidya Joshi ◽

Brian Noga ◽

Rob Schultz ◽

...

Keyword(s):

Drug Delivery ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Dose Inhaler ◽

Metered Dose Inhaler ◽

Delivery Performance ◽

Metered Dose ◽

Dose Combination

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Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow

Blood ◽

10.1182/blood-2010-04-278192 ◽

2010 ◽

Vol 116 (15) ◽

pp. e66-e73 ◽

Cited By ~ 104

Author(s):

Chih-Wen Ni ◽

Haiwei Qiu ◽

Amir Rezvan ◽

Kihwan Kwon ◽

Douglas Nam ◽

...

Keyword(s):

Carotid Artery ◽

Ex Vivo ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Gene Expression Profiles ◽

Disturbed Flow ◽

A Genome ◽

Pattern Comparison

Abstract Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.

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