An In Silico Investigation of a Lobe-Specific Targeted Pulmonary Drug Delivery Method

2018 ◽  
Author(s):  
Yu Feng ◽  
Xiaole Chen ◽  
Mingshi Yang
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Lung Tumor ◽  
Deposition Efficiency ◽  
Pulmonary Drug Delivery ◽  
Operational Flexibility ◽  
Delivery Method ◽  
Key Factor ◽  
The Right ◽  
Drug Delivery Devices

Nowadays, “personalized medicine” is starting to replace the current “one size fits all” approach. The goal is to have the right drug with the right dose for the right patient at the right time and location. Indeed, conventional pulmonary drug delivery devices still have poor efficiencies (<25%) for delivering drugs to the lung tumor sites. Major portions of the aggressive medicine deposit on healthy tissue, which causes severe side effects and induces extra health care expenses. Therefore, a new targeted pulmonary drug delivery method is proposed and evaluated using the Computational Fluid-Particle Dynamics (CFPD) method to achieve the lobe-specific delivery. By controlling the release position and velocity of the drug particles at the mouth inlet, drug deposition efficiency (DE) in a designated lobe can be increased up to 90%. Intersubject variability has also been investigated using the noninvasive in silico tool. Results indicate that the glottis constriction ratio is a key factor to influence the effectiveness of the purposed targeted drug delivery method. Although lobe-specific pulmonary drug delivery can be realized, the actuation flow rate must be lower than 2 L/min, and the glottis constriction ratio has a significant impact on the effectiveness of the targeting method. Also, a design idea using e-cigarette as the prototype is proposed as the next-generation inhaler to accommodate the operational flexibility restrictions.

scholarly journals In Silico Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 230 ◽  
Author(s):  
Lihi Shachar-Berman ◽  
Saurabh Bhardwaj ◽  
Yan Ostrovski ◽  
Prashant Das ◽  
Pantelis Koullapis ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Respiratory Tract ◽  
In Silico ◽  
Dry Powder Inhaler ◽  
Deposition Efficiency ◽  
Pulmonary Drug Delivery ◽  
Spherical Particles ◽  
Inhalation Therapy ◽  
Equivalent Diameter ◽  
Upper Airways

Motivated by a desire to uncover new opportunities for designing the size and shape of fiber-shaped aerosols towards improved pulmonary drug delivery deposition outcomes, we explore the transport and deposition characteristics of fibers under physiologically inspired inhalation conditions in silico, mimicking a dry powder inhaler (DPI) maneuver in adult lung models. Here, using computational fluid dynamics (CFD) simulations, we resolve the transient translational and rotational motion of inhaled micron-sized ellipsoid particles under the influence of aerodynamic (i.e., drag, lift) and gravitational forces in a respiratory tract model spanning the first seven bifurcating generations (i.e., from the mouth to upper airways), coupled to a more distal airway model representing nine generations of the mid-bronchial tree. Aerosol deposition efficiencies are quantified as a function of the equivalent diameter (dp) and geometrical aspect ratio (AR), and these are compared to outcomes with traditional spherical particles of equivalent mass. Our results help elucidate how deposition patterns are intimately coupled to dp and AR, whereby high AR fibers in the narrow range of dp = 6–7 µm yield the highest deposition efficiency for targeting the upper- and mid-bronchi, whereas fibers in the range of dp= 4–6 µm are anticipated to cross through the conducting regions and reach the deeper lung regions. Our efforts underscore previously uncovered opportunities to design the shape and size of fiber-like aerosols towards targeted pulmonary drug delivery with increased deposition efficiencies, in particular by leveraging their large payloads for deep lung deposition.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy

2017 ◽  
Vol 23 (3) ◽  
pp. 454-466 ◽  
Author(s):  
Daniele R. Nogueira-Librelotto ◽  
Cristiane F. Codevilla ◽  
Ammad Farooqi ◽  
Clarice M. B. Rolim
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Therapeutic Benefit ◽  
Active Targeting ◽  
Future Research ◽  
Passive Targeting ◽  
The Right ◽  
Review Current ◽  
Target Effects

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research.

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

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