Novel extended <i>in vitro-in vivo</i> correlation model for the development of extended-release formulations for baclofen: From formulation composition to <i>in vivo</i> pharmacokinetics

Kim, Tae Hwan,Bulitta, Jü,rgen B.,Kim, Do-Hyung,Shin, Soyoung,Shin, Beom Soo Elsevier 2019 International journal of pharmaceutics Vol.556 No.-

<P><B>Abstract</B></P> <P> <I>In vitro-in vivo</I> correlation (IVIVC), a predictive mathematical model between the <I>in vitro</I> dissolution and the <I>in vivo</I> pharmacokinetics has been utilized for the development of new extended release (ER) formulations. The aim of the present study was to extend the IVIVC approach, which correlates among the formulation composition, the <I>in vitro</I> dissolution, and the plasma drug concentration, to predict plasma drug concentrations from a given composition of the formulation, and vice versa, using baclofen as a model drug. Baclofen ER tablets with different dissolution rates were prepared by varying the composition of hydroxypropyl methylcellulose (HPMC). First, the HPMC compositions and the corresponding <I>in vitro</I> dissolutions parameters were correlated, and then the <I>in vitro</I> dissolution parameters were correlated with the <I>in vivo</I> dissolution parameters extracted from the pharmacokinetic profiles of the baclofen ER formulations <I>via</I> population pharmacokinetic modeling. The final extended IVIVC model linked the composition of the formulation, the <I>in vitro</I> dissolution, and the <I>in vivo</I> plasma concentration profile and was successfully applied for the prediction of <I>in vivo</I> pharmacokinetics from the amount of HPMC in baclofen ER formulations. The present approach holds great promise for designing optimal compositions of ER formulations to present desired plasma concentration profile.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Lung Organoids: Systematic Review of Recent Advancements and its Future Perspectives

Thangam T.,Parthasarathy Krupakar,Supraja K.,Haribalaji V.,Sounderrajan Vignesh,Rao Sudhanarayani S.,Jayaraj Sakthivel 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.5

Organoids are essentially an in vitro (lab-grown) three-dimensional tissue culture system model that meticulously replicates the structure and physiology of human organs. A few of the present applications of organoids are in the basic biological research area, molecular medicine and pharmaceutical drug testing. Organoids are crucial in connecting the gap between animal models and human clinical trials during the drug discovery process, which significantly lowers the time duration and cost associated with each stage of testing. Likewise, they can be used to understand cell-to-cell interactions, a crucial aspect of tissue biology and regeneration, and to model disease pathogenesis at various stages of the disease. Lung organoids can be utilized to explore numerous pathophysiological activities of a lung since they share similarities with its function. Researchers have been trying to recreate the complex nature of the lung by developing various “Lung organoids” models. This article is a systematic review of various developments of lung organoids and their potential progenitors. It also covers the in-depth applications of lung organoids for the advancement of translational research. The review discusses the methodologies to establish different types of lung organoids for studying the regenerative capability of the respiratory system and comprehending various respiratory diseases. Respiratory diseases are among the most common worldwide, and the growing burden must be addressed instantaneously. Lung organoids along with diverse bio-engineering tools and technologies will serve as a novel model for studying the pathophysiology of various respiratory diseases and for drug screening purposes. Organoids are essentially an in vitro (lab-grown) three-dimensional tissue culture system model that meticulously replicates the structure and physiology of human organs. A few of the present applications of organoids are in the basic biological research area, molecular medicine and pharmaceutical drug testing. Organoids are crucial in connecting the gap between animal models and human clinical trials during the drug discovery process, which significantly lowers the time duration and cost associated with each stage of testing. Likewise, they can be used to understand cell-to-cell interactions, a crucial aspect of tissue biology and regeneration, and to model disease pathogenesis at various stages of the disease. Lung organoids can be utilized to explore numerous pathophysiological activities of a lung since they share similarities with its function. Researchers have been trying to recreate the complex nature of the lung by developing various “Lung organoids” models. This article is a systematic review of various developments of lung organoids and their potential progenitors. It also covers the in-depth applications of lung organoids for the advancement of translational research. The review discusses the methodologies to establish different types of lung organoids for studying the regenerative capability of the respiratory system and comprehending various respiratory diseases. Respiratory diseases are among the most common worldwide, and the growing burden must be addressed instantaneously. Lung organoids along with diverse bio-engineering tools and technologies will serve as a novel model for studying the pathophysiology of various respiratory diseases and for drug screening purposes.

Models of Respiratory Infections: Virus-Induced Asthma Exacerbations and Beyond

Sara Saturni,Marco Contoli,Antonio Spanevello,Alberto Papi 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.6

Respiratory infections are one of the main health problems worldwide. They are a challenging field of study due to an intricate relationship between the pathogenicity of microbes and the host’s defenses. To better understand mechanisms of respiratory infections, different models have been developed. A model is the reproduction of a disease in a system that mimics human pathophysiology. For this reason, the best models should closely resemble real-life conditions. Thus, the human model is the best. However, human models of respiratory infections have some disadvantages that limit their role. Therefore, other models, including animal, in vitro, and mathematical ones, have been developed. We will discuss advantages and limitations of available models and focus on models of viral infections as triggers of asthma exacerbations, viral infections being one of the most frequent causes of exacerbating disease. Future studies should focus on the interrelation of various models.

Model-based drug development: application of modeling and simulation in drug development

김태환,신소영,신범수 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.4

Despite enormous success in biomedical science and technology, as well as increased research and development spending, pharmaceutical productivity has faced challenges. The success rates in drug development remain low and have shown a declining trend in the last two decades. The US FDA has also recognized the inefficiency in drug development and proposed model-based drug development (MBDD) to improve pharmaceutical productivity and decision making. Modeling and simulation provide a powerful tool to summarize and integrate information from different studies. Application of modeling and simulation can help decision making, design better studies, reduce costs, save time, and ultimately improve success rates. Beyond traditional types of modeling techniques or applications, MBDD is a paradigm that covers the entire spectrum of the drug development process. This review aims to provide an overview of modeling and simulation and their application to various drug development processes, from early discovery to preclinical and clinical stages, as well as formulation optimization. Several types of models will be discussed, and illustrative examples of their applications in the drug development process will be highlighted.

In vitro 3D skin model using gelatin methacrylate hydrogel

곽봉신,최원호,전중원,원종인,성건용,김범상,성종환 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.66 No.-

Interests in in vitro skin models have been growing. Collagen, which is a main scaffold material for in vitro 3D skin models, has weak mechanical properties, often resulting in undesirable contraction. The physiological characteristics of the skin models often depend on the matrix in which cells are cultured. In this study, we developed a 3D skin model using gelatin methacrylate. The mechanical and transport properties were studied, and attachment and growth of fibroblasts and keratinocytes were examined. Fibroblasts preferred softer matrix, whereas HaCaT cells preferred harder matrix of gelatin methacrylate. This study provides information for developing in vitro skin models.

<i>In vitro</i> 3D skin model using gelatin methacrylate hydrogel

Kwak, Bong Shin,Choi, Wonho,Jeon, Joong-won,Won, Jong-In,Sung, Gun Yong,Kim, Bumsang,Sung, Jong Hwan Elsevier 2018 Journal of industrial and engineering chemistry Vol.66 No.-

<P><B>Abstract</B></P> <P>Interests in <I>in vitro</I> skin models have been growing. Collagen, which is a main scaffold material for in vitro 3D skin models, has weak mechanical properties, often resulting in undesirable contraction. The physiological characteristics of the skin models often depend on the matrix in which cells are cultured. In this study, we developed a 3D skin model using gelatin methacrylate. The mechanical and transport properties were studied, and attachment and growth of fibroblasts and keratinocytes were examined. Fibroblasts preferred softer matrix, whereas HaCaT cells preferred harder matrix of gelatin methacrylate. This study provides information for developing <I>in vitro</I> skin models.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

시험관내 역동모델을 이요한 Klebsiella Pneumoniae에 대한 Ceftriaxone과 Amikacin의 병용요법

이동건,최정현,유진홍,신완식,허동호 大韓臨床藥理學會 1999 臨床藥理學會誌 Vol.7 No.1

Trends in the development of human stem cell-based non-animal drug testing models

Su-Jin Lee,Hyang-Ae Lee 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.6

In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

In vitro and in vivo studies on theophylline mucoadhesive drug delivery system

Bandyopadhyay, AK,Perumal, P Kyung Hee Oriental Medicine Research Center 2007 Oriental pharmacy and experimental medicine Vol.7 No.1

Mucus is an aqueous gel complex with a constitution of about 95% water, high molecular weight glycoprotein (mucin), lipid, salts etc. Mucus appears to represent a significant barrier to the absorption of some compounds. Natural mucoadhesive agent was isolated and purified from the aqueous extract of the seeds of prosopis pallida (PP). Formulated tablet with the isolated material by wet granulation method. Some natural edible substances are in consideration for candidates as mucoadhesive agents to claim more effective controlled drug delivery as an alternative to the currently used synthetic mucoadhesive polymers. Subjected the materials obtained from natural source i.e. PP and standard synthetic substance, sodium carboxymethyl cellulose for evaluation of mucoadhesive property by various in vitro and in vivo methods. Through standard dissolution test and a model developed with rabbit, evaluated in vitro controlled release and bioadhesive property of theophylline formulation. Mucoadhesive agent obtained from PP showed good mucoadhesive potential in the demonstrated in vitro and in viνo models. The results suggest that the mucoadhesive agent showed controlled release properties by their application, substantially. In order to assess the gastrointestinal transit time in vivo, a radio opaque X-ray study performed in healthy rabbit testing the same controlled release formulation with and without bioadhesive polymer. Plasma levels of theophylline determined by the HPLC method and those allowed correlations to the in vitro mucoadhesive study results. Better correlation found between the results in different models. PP may acts as a better natural mucoadhesive agent in the extended drug delivery system.

Tissue Engineered Mini-Cornea Model for Eye Irritation Test

Kim Seon-Hwa,Jo Sung-Han,Kim Byeong Kook,Park Sang-Hyug 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.2

BACKGROUND: Eye irritation tests with animals have been conducted for a long time. However, the subjective decision to irritation, the anatomic/physiologic difference between species and humans, and ethical issues are crucial problems. Various research groups have paid attention to alternative testing methods. In these senses, we fabricated in vitro minicornea models with immortalized human corneal epithelial cells (iHCECs) and keratocytes (iHCKs) and used them for irritation tests. This study hypothesized that our mini-cornea model could present different viability tendencies according to test chemicals with different irritancy levels. METHODS: Cells used in this study were characterized with cornea-specific markers by immunocytochemistry and western blot. To make a three-dimensional hemisphere construct like cornea stroma, we cultured iHCKs under modified culture conditions verified by matrix formation and total collagen content. iHCECs were seeded on the construct and cultured at an air–liquid interface. The model was treated with 2-phenoxyethanol, triton X-100, sodium lauryl sulfate, and benzalkonium chloride. RESULTS: iHCECs and iHCKs presented their specific cell markers. In modifying the culture condition, the group treating ascorbic acid (200 lg/ml) presented an intact cellular matrix and included the highest collagen content; thus, we used this condition to fabricate the mini-cornea model. The model shows hemisphere shape and homogenous cell distributions in histological analysis. We observed different sensitivity tendencies by types of chemicals, and the model’s viability significantly decreased when the chemical concentration increased. CONCLUSION: In this study, we performed and observed irritation tests using a tissue-engineered mini-cornea model and considered to apply as an alternative approach for animal tests.