Computer-Assisted Drug Formulation Design: Novel Approach in Drug Delivery

Metwally, Abdelkader A.; Hathout, Rania M.

doi:10.1021/mp500740d

Cited by 88 publications

(58 citation statements)

References 36 publications

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“…In this present work, we use curcumin as a model drug and aim to provide a novel approach for enhancing the chemical stability of drug molecules loaded in liposome. It is well known that curcumin is a lipophilic molecule and has been extensively used in food, medicines, and cosmetics due to its various bioactivities [17][18][19][20][21]. However, its delivery is highly limited by its insolubility and instability in biological fluids [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug

et al. 2017

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Liposome is a promising carrier system for delivering bioactive molecules. However, the successful delivery of pH-sensitive molecules is still limited by the intrinsic instability of payloads in physiological environment. Herein, we developed a special liposome system that possesses an acidic micro-environment in the internal aqueous chamber to improve the chemical stability of pH-sensitive payloads. Curcumin-loaded liposomes (Cur-LPs) with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared. These Cur-LPs have similar particle size of 300 nm, comparable physical stabilities and analogous in vitro release profiles. Interestingly, the chemical stability of liposomal curcumin in 50% fetal bovine serum and its anticancer efficacy in vitro are both micro-environmental pH-dependent (Cur-LP-2.5 > Cur-LP-5.0 > Cur-LP-7.4). This serum stability still has space to be further enhanced to improve the applicability of Cur-LP. In conclusion, creating an acidic micro-environment in the internal chamber of liposome is feasible and efficient to improve the chemical stability of pH-sensitive payloads.

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Section: Introductionmentioning

confidence: 99%

Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug

et al. 2017

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“…Rheological measurements. The viscosity of different concentrations of gelatin in water (4,8,12,16, and 20 mg/mL) Correspondence to: R. M. Hathout, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, African Union Authority Street, Abbassia, Cairo 11566, Egypt; e-mail: r_hathout@yahoo.com or rania.hathout@pharma.asu.edu.eg was determined using a DV-E Viscoometer (Brookfield Engineering Laboratories, Middleboro, MA, USA) using a 61 spindle at speeds ranging from 0.5 to 200 rpm at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…6,7 The method was proven highly accurate and robust compared to the other machine learning methods. 8…”

Section: Introductionmentioning

confidence: 99%

Gelatinized‐core liposomes: Toward a more robust carrier for hydrophilic molecules

Hathout

Gad

Metwally

2017

J Biomedical Materials Res

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The use of liposomes as a delivery system for hydrophobic and hydrophilic drugs is well recognized. However, they possess several limitations that remained unresolved, including stability problems, low entrapment of the hydrophilic drugs, and the subsequent rapid release. This study introduces a novel approach to incorporate gelatin in the liposomal core to overcome these limitations. A rheological study was conducted to select suitable masses of the gelatin used in the liposomal formulations. Moreover, a full-factorial experimental design was utilized to compare the newly produced gel-core liposomes to the conventional liposomes with respect to the amount of a model hydrophilic molecule loading. An advanced machine learning method, namely, artificial neural networks was utilized to capture the effects of gelatin and cholesterol incorporation in the liposomes on the entrapment efficiency. The results revealed the successful preparation of the novel vesicles and their superiority over the conventional liposomes in drug loading, sustaining the drug release and stability which pose the newly introduced liposomal system as a successful delivery carrier for hydrophilic molecules and drugs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3086-3092, 2017.

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“…The percentages bias were less than 10% confi rming our hypothesis that the proper usage of molecular dynamics simulations and docking experiments can replace the tedious effort, time and money consuming wet-lab experiments. We introduced this new insight as what we called "Computer-assisted drug formulation design" in a manuscript that was published in 2015 in the prestigious journal "Molecular Pharmaceutics" [1]. We believe that this approach should be implemented in all forthcoming formulation studies.…”

Section: Editorialmentioning

confidence: 99%

Exploiting databases and computer softwares in drug formulation: Mining the treasures

Hathout¹,

Metwally²

2018

Open J Chem

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EditorialIn one of the conversations between me and one of my senior colleagues, she told me "What lucky researchers you are!", interested to know the reason behind this statement, I asked: "Why?!", and she replied: "because in our time we didn't have all these available search engines, scientifi c databases, open resources and data manipulation tools". Later, I had a discussion with one of my colleagues -now we are coauthors -who expressed his interest in examining new aspects of formulation: "we can use computer simulations to examine many aspects of different formulations, literally virtualizing our lab" he said.We gave this conversation some thorough thinking (actually thinking outside the box!) which led us to the interesting conclusion; that though we truly have all these data resources, yet, we still perform our research studies in the most common traditional way. What have we done with all these treasures? Why can't we correlate the results obtained from different studies together? Why can't we start our studies in a different way other than the traditional try-and-error and the wet experimentation screening of the available drugs and/or carriers in different conditions and performing several modifi cations reaching our objectives whether; high loading or sustained release or targeting or whatsoever? We came up with the convincement that the advancement in technology and computer science programs should be refl ected in the drug delivery and formulation sciences in the most intelligent way. This should be attained to fulfi l the ultimate goal for all scientists to leave their experimental results all over the years as footsteps for followers to walk on.According to the questions that were aroused in our mind based on the above conversation, we started performing a new project aiming at exploiting previous results obtained from different research groups and correlating these results through computational pharmaceutics and predictive modelling aiming to reach different and novel conclusions. Indeed, the data available in literature are treasures, but they need mining and effi cient utilization to extract the desired information.The story went as follows with our fi rst research project:we fi rst concentrated on one common carrier viz. solid lipid nanoparticles (SLN) comprising one lipid: Tripalmitin ® , in particular, and adopted "data mining" of already published results to answer the following question: Could we predict the encapsulation effi ciency of a drug in SLN? Through searching the different scientifi c databases such as: Pubmed, ISI web of science and google scholar, we collected the published research results regarding the different drugs loadings. We then 'virtualized' our system by simulating the investigated carrier through molecular dynamics using the open-source software Gromacs. We prepared the chemical structures of the reported drugs and performed energy minimization to search for the lowest energy conformer. The interesting part came up when we docked the constructed drugs on the simulat...

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Computer-Assisted Drug Formulation Design: Novel Approach in Drug Delivery

Cited by 88 publications

References 36 publications

Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug

Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug

Gelatinized‐core liposomes: Toward a more robust carrier for hydrophilic molecules

Exploiting databases and computer softwares in drug formulation: Mining the treasures

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