Interfacial Phenomena In Drug Delivery And Targeting Pdf

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Metrics details. Surface tension at the surface-to-air interface is a physico-chemical property of liquid pharmaceutical formulations that are often overlooked. To determine if a trend between surface tension and route of administration exists, a suite of oral, nasal, and ophthalmic drug formulations were analyzed.

Enabling cytoplasmic delivery and organelle targeting by surface modification of nanocarriers

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Local implantable drug delivery system IDDS can be used as an effective adjunctive therapy for solid tumor following thermal ablation for destroying the residual cancer cells and preventing the tumor recurrence.

In this model, doxorubicin DOX -loaded implant act as a transmitter is assumed to be inserted inside solid tumor acts as a channel after thermal ablation. Using this model, we can predict the extracellular and intracellular concentration of both free and bound drugs.

Also, Impact of the anticancer drug on both cancer and normal cells is evaluated using a pharmacodynamic PD model that depends on both the spatiotemporal intracellular concentration as well as characteristics of anticancer drug and cells. Accuracy and validity of the proposed drug transport model is verified with published experimental data in the literature. The results show that this combination therapy results in high therapeutic efficacy with negligible toxicity effect on the normal tissue.

The proposed model can help in optimize development of this combination treatment for solid tumors, particularly, the design parameters of the implant.

Cancer is one of the most dangerous and deadliest diseases that cause deaths of millions of people around the world each year. Minimally invasive and image-guided thermal ablation techniques such as radiofrequency ablation RFA and high-intensity focused ultrasound HIFU ablation have been used for local treatment of malignant solid tumors as an alternative for systemic chemotherapy and surgical resection 2. Thus, thermal ablation will destroy the cellular and vasculature structures, which results in a new ablated tissue with different characteristics.

However, the main limitation and challenge of thermal ablation is the risk of local recurrence and residual tumor after the thermal ablation, particularly at the tumor periphery 3 , 4 , 5.

The experimental studies showed that the combination therapy through local release of anticancer drugs from a miniaturized implant in solid tumors following thermal ablation can result in a better therapeutic efficacy by destroying the residual cancer cells and preventing tumor recurrence 6 , 7 , 8.

Anticancer drug distribution and fluid flow within solid tumors are essential factors that affect the clinical efficiency of anticancer therapies. Moreover, one of the most important challenges in the development of new drug delivery systems DDSs is ensuring that the optimal amount of drug is achieved in tumor versus normal tissues to avoid toxicity in the healthy tissues. Dual-release implants have been clinically approved and currently used for cancer treatments in the clinical trials and research, e.

The implant releases the anticancer drug over two phases, namely, burst and sustained releases. For example, in-situ forming implants ISFIs have a dual-release pattern with a large undesirable burst release, which may cause major toxicity problems and consume the loaded drug in the implants rapidly Designing this type of implants with a minimum initial burst release becomes an attractive challenge, and one of the key issues in the design of ISFIs Moreover, some drug-loaded implants can be designed in a controlled way to have a dual-release profile to release a large amount of drug early, i.

Therefore, providing mathematical pharmacodynamic PD and pharmacokinetic PK models to examine and analyze the impact of the anticancer drug on the surrounding healthy and tumor tissues is necessary for design the implantable DDSs to get high therapeutic efficiency.

Mathematical and computational modelling of release and transport of anticancer drugs have played a vital role in the advancement of drug delivery systems. These models provide a powerful tool for understanding drug transport and other complex pharmacokinetics processes and their impact on the tumor cells and the surrounding tissues pharmacodynamics. As a result, they can help in optimum design and development of the DDSs to reduce the number of animal experiments which save time and reduce cost.

A comprehensive review of literature has been discussed on mathematical models that have been employed to improve and design anti-cancer DDSs 13 , 14 , For example, mathematical models were used to aid the design and optimization of doxorubicin-loaded liposome formulations to achieve a better therapeutic index in tumor Application of mathematical modeling to guide the development of various drug delivery systems, e.

These models optimized the drug formulation and dose regimen, accelerated the clinical trial, evaluated the influence of the drug on anti-tumor efficacy, predicted the clinical response by preclinical data, etc.

A generic model is developed to minimize the number of suppositions about drug distribution to describe the behavior of therapeutic and diagnostic drugs in tumor environments Furthermore, a mathematical model is developed to study the effect of the various factors on the delivery of BCNU chemotherapy to brain tumor using systemic administration and local release from Gliadel wafer This model yields information on the optimal polymer implant location and the efficacy of controlled drug delivery by Gliadel wafer compared to traditional degradable polymers.

Most of the mathematical works on anticancer drug transport are limited to systemic drug delivery while few simplified models on implantable drug delivery systems IDDSs following thermal ablation are reported 12 , 20 , A mathematical model was derived at steady-state for design dual-release doxorubicin DOX -loaded implant to provide the optimal drug pharmacokinetics at the tumor ablation boundary after RFA A numerical model was proposed to estimate the DOX drug transport parameters, e.

A computational transport model was proposed for simulation and prediction transport and pharmacokinetics of DOX after inserting biodegradable implants in liver tumors following RFA 20 , 21 , However, the models discussed above are derived based on many simplified assumptions, such as taking the impact of pharmacokinetics e.

These models do not characterize and predict the dynamic intracellular concentration of anticancer drugs and the binding of anticancer drugs with proteins in the tissue. Furthermore, the works mentioned above do not provide any pharmacodynamic model which can be used for evaluating the therapeutic efficacy, i. In this paper, we develop a comprehensive mathematical and computational model for local release and transport of anticancer DOX drug following insertion of a dual-release implant inside a thermally ablated solid tumor with the help of molecular communication MC abstraction, see Fig.

We chose DOX anticancer drug because it is widely used in chemotherapy due to its efficacy in killing a wide range of cancers such as carcinomas, sarcomas, and hematological cancers Moreover, there are many experimental measured parameters for DOX in the literature which can be used in our models to get more accurate results.

However, the proposed model can be applied to other drugs by adjusting the drug parameters in the model. Molecular communication is an emerging paradigm for exchange the biochemical molecules between the biological cells and synthetic nanomachines within the biological aqueous environments 25 , One of the most important applications of the MC paradigm is modelling and abstraction of the drug delivery systems, particularly for providing the drug at the site of action and minimizing the drug in the healthy tissues 25 , In this paradigm, the drug delivery process is abstracted as a communication mechanism, as shown in Fig.

The implantable drug delivery device the implant acts as a transmitter while the target site, i. The anticancer therapeutic agent, i. The tumor microenvironment is a three-dimensional 3-D medium surrounded by normal tissue, which acts as a molecular communication channel.

At the target sites, the intracellular concentration of the anticancer drug DOX should reach a minimum threshold to kill the cancer cells. In the MC paradigm, this can be considered as a reception mechanism where the intracellular concentration is the received signal, while the death of cancer cells is the output response.

Abstraction of the implantable drug delivery system in tumor using molecular communication paradigm. In this model, a millimeter-scale dual-release implant, loaded with anticancer DOX drug, is assumed to be inserted inside a solid tumor to releases DOX anticancer agents. Here, we consider two solid tumor models, namely, thermally ablated and non-ablated tumors, surrounded by normal tissues. Impacts of all the above-mentioned pharmacokinetic processes are included in the drug transport model for predicting the extracellular and intracellular concentrations of both free and bound DOX.

Furthermore, this model enables estimate the toxicity of DOX on tumor cells and surrounding healthy tissue. The impact of DOX on the cancer cells is evaluated using a pharmacodynamic model that depends on the spatiotemporal intracellular concentration of DOX as well as on the characteristics of both the DOX and tumor cells. Moreover, the concentration of DOX in normal tissue is evaluated, which can be used for toxicity assessment. Accuracy and validity of our proposed model are verified and compared with the published experimental data in the literature, assuming the impact of the various pharmacokinetic parameters are combined in the apparent diffusivity and apparent elimination constant.

To the best of our knowledge, this work is the first comprehensive model available in the literature that simultaneously captures and addresses the anticancer drug transport, pharmacokinetics, and pharmacodynamics using local dual-release drug implants in malignant solid tumors following thermal ablation.

In this study, the governing mathematical equations which describe the proposed model are discretized in space with the finite element method using the commercial software package COMSOL Multiphysics 5. The steady-state solutions of the interstitial velocity and pressure fields are applied to the drug transport model. Both the fluid flow and the drug transport models are solved under relative tolerance of 10 —6 and absolute tolerance 10 —7.

In this model, the tumor characteristics and the drug parameters are taken from the published experimental works and other studies in the literature. The parameters used in this study are given in Tables 2 , 3 , 4 and 5. As shown in Fig. Furthermore, there is a sharp pressure gradient and consequently, high-velocity field at the interface boundary between the tumor and normal tissues, as shown in Fig.

This result is not surprising due to the lake of the lymph vasculature in the tumor compared to the normal tissue. The trend of the results agrees well with the previous studies in the literature 1 , 27 , A group of researchers conducted experiments for measuring the DOX concentration with the distance from polymer implants placed inside thermally ablated liver tumor 8 , 20 , 21 , In Fig.

The impact of the various processes in the tumor, including the binding effect, is given in terms of the apparent elimination rate constant and apparent diffusivity The parameters used in this comparison are chosen to be the same as that used in the experiment As expected, the measured concentration shows a decreasing trend with the radial distance from the implant. The results obtained using our numerical COMSOL model agree well with the results extracted from the published experimental data.

This indicates the accuracy and validity of the drug release and transport model, which represents the main part of the proposed model in this paper. Comparison of DOX concentration obtained from the experimental data 21 with our models using apparent diffusivity and apparent elimination rate. Therefore, we do not show all the results in this paper to eliminate the redundancy. The implant with a higher release rate leads to a larger peak concentration and lower peak time. As the release rate increases, the amount of the released DOX will increase rapidly, and thus the peak concentration will reach a higher value within a shorter time.

The increasing and decreasing rates of the extracellular concentration become sharper as the release rate constant increases.

The decay in concentration after it reaches the peak value is due to a reduction in the released drug from the implant and elimination through blood vessels and cellular uptake. The bound-DOX concentration has a similar trend as the free-DOX concentration for various sustained release rate constants but with approximately three-fold higher amplitude. The extracellular DOX concentration in a solid tumor without applying thermal ablation has a smaller amplitude than the concentration in an ablated tumor.

This happens because in the non-ablated tumor, the cells and blood vasculature structures, which cover a large volume of the solid tumor, have a high impact on the elimination of the DOX through the cellular uptake and the blood microvessels.

Furthermore, the drug can penetrate a larger distance and cover a larger volume in the ablated tumor compared to the non-ablated tumor. Also, tumor with larger ablation radius e. The observed impact of the thermal ablation on the drug distribution in tumors agrees with the experimental data in the literature 6 , 8 , The DOX intracellular concentration follows a similar trend as the extracellular concentration because it highly depends on the extracellular DOX levels. The higher peak amplitude of the intracellular concentration can be achieved using a faster release implant.

This happens because the extracellular DOX concentration decreases with the distance, and it has a direct influence on the intracellular uptake and, consequently, on the intracellular DOX concentration. Tumor cell density shows heterogeneous distribution along the radial direction, where it increases with the distance with minimum density appears near the inner boundary of the risk region.

This can also be seen in the color map of the spatial distribution of tumor cell density in Fig. Moreover, there is a significant reduction in tumor cell density over time following the insertion of the implant. However, using a smaller release rate will consume less amount of the drug with minimum toxicity on the normal tissue. Therefore, design the implant with an optimal release rate is very important to get a high therapeutic efficacy. The final therapeutic outcomes of the combination therapy using the DOX-loaded implant and RFA can be obtained from the tumor survival curves, as shown in Fig.

Surface tension examination of various liquid oral, nasal, and ophthalmic dosage forms

Herein, the interaction among the antidepressant drug amitriptyline hydrochloride AMT and a green gemini surfactant, ethane-1, 2-diyl bis N,N-dimethyl-N-tetradecylammoniumacetoxy dichloride E , via numerous techniques such as tensiometry, fluorimetry, FT-IR and UV-visible spectroscopy in three different media aqueous 0. AMT is used to treat mental illness or mood problems, such as depression. The aggregation of biologically active ingredients can enhance the bioavailability of hydrophobic drugs. The decrease in cmc indicates the nonideality of studied mixtures of different compositions. Although, employed drug AMT is freely soluble in the aqueous and non-aqueous system but is not hydrophobic enough to act as its carrier.

Interfaces are of vital importance in many fields of application, but the phenomena are hard to visualize, and the theories are often linked to complex mathematical models. This volume provides students and working scientists with a readable book on interfacial phenomena. It addresses the subject in a manner which should make it accessible to the scientist without previous experience of interfacial science. The book addresses a wide range of pharmaceutical issues, ranging from product development to research linked to in vivo applications. My Account Sign In Register for an account. Personal ordering now live! Educational customers login to see your trade pricing.

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Interfacial phenomena in drug delivery and targeting

 Потому что дело именно в. Он что-то скрывает. Джабба вытаращил глаза: - Мидж, дорогая. Я по уши опутан кабелем.

Именно он и подал ручную команду на отзыв Следопыта. Вопрос насколько. уступил место другому - с какой целью?. У Хейла не было мотивов для вторжения в ее компьютер. Он ведь даже не знал, что она задействовала Следопыта.

Слова Сьюзан словно парализовали его, но через минуту он возобновил попытки высвободиться. - Он убьет. Я чувствую.

Он стал ждать, когда его компьютер разогреется, и Сьюзан занервничала.

 Хорошо, - сказала.  - Я немного погорячилась. - Немного? - Глаза Бринкерхоффа сузились.  - У Стратмора стол ломится от заказов.

Она шла следом за ним точно в тумане. Коридор, выложенный кафельными плитками, довольно круто спускался вниз, и Сьюзан держалась за перила, стараясь не отставать. Воздух в помещении становился все прохладнее. Чем глубже под землю уходил коридор, тем уже он становился.

 - Я попросил Фонтейна передать его наследникам Танкадо.  - Он взял ее руку и натянул что-то на палец. - Лжец, - засмеялась Сьюзан, открывая.  - Я же угада… - Но она замолкла на полуслове.

А как же проваливай и умри. ГЛАВА 36 Ручное отключение. Сьюзан отказывалась что-либо понимать. Она была абсолютно уверена, что не вводила такой команды - во всяком случае, намеренно.

 Вы уничтожите этот алгоритм сразу же после того, как мы с ним познакомимся. - Конечно. Так, чтобы не осталось и следа. Сьюзан нахмурилась.

 Кого? - спросил он чуть осипшим голосом. - Кармен. Ту, что работает в столовой. Бринкерхофф почувствовал, как его лицо заливается краской. Двадцатисемилетняя Кармен Хуэрта была поваром-кондитером в столовой АН Б.

Он поклялся применять все свои знания, весь опыт, всю интуицию для защиты компьютеров агентства, стоивших не один миллион долларов. - Интуиция? - с вызовом проговорил. Не нужно интуиции, чтобы понять: никакая это не диагностика.

 - Вам нужна сопровождающая. - Да-да. Сегодня мой брат Клаус нанял девушку, очень красивую. С рыжими волосами. Я тоже хочу.

 - Скажем, принести пару таблеток валиума. Наконец канадец опомнился. - Из консульства? - Его тон заметно смягчился. Беккер кивнул. - Так, значит, вы не по поводу моей колонки.

 Замечательно.

5 Comments

  1. Miki T. 10.02.2021 at 10:44

    This format is currently out of stock. ISBN Published February 11, by CRC Press. Pages. ISBN

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  3. Anna T. 14.02.2021 at 02:33

    Interfacial Phenomena in Drug Delivery and Targeting. FULL ACCESS. Book eBook Published 21 April Pub. Location eBook ISBN

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    Salvatore , Naples, Italy.

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