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Our drug discovery approach in the pre-clinical development phase in context of the whole drug discovery programme.
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Identifying novel compounds or improving bioavailability of drugs requires extensive screening,
in vitro
and
in vivo
testing and subsequent commercialisation. Traditional methods can be labour
intensive and time-consuming. Use of modern technologies can reduce these challenges and is best
achieved through collaboration with researchers speciali...
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Prefaţă
Lucrarea de faţă, având ca autor pe domnul conferenţiar universitar doctor Dumitru Deleanu, este elaborată pe baza programei analitice a disciplinei „Mecanisme” şi se adresează studenţilor Facultăţii de Electromecanică Navală a Universităţii Maritime din Constanţa. Conţinutul lucrării dovedeşte faptul că autorul a înţeles modul modern de...
Data-to-text generation can be conceptually divided into two parts: ordering and structuring the information (planning), and generating fluent language describing the information (realization). Modern neural generation systems conflate these two steps into a single end-to-end differentiable system. We propose to split the generation process into a...
Citations
... Synthetic drugs for infammation management, such as nonsteroidal anti-infammation drugs (NSAIDs), demonstrated symptom relief but with serious consequences and side efects that endangered life [4,5]. Since ancient times, the natural by-products from medicinal plants and their secondary metabolites have been used to treat several infammatory disorders due to their safety compared with synthetic drugs [6,7]. ...
Te use of standard synthetic medications to treat infammatory illnesses is associated with several negative efects. It has been shown that medicinal plants and their by-products are useful for safely treating infammation. Herein, the essential oil of Eugenia supra-axillaris (family: Myrtaceae, ESA-EO) was isolated and further chemically characterized by GC-MS, and then, its nanoemulsion (ESA-EO-NE) was prepared. In addition, the anti-infammation against the carrageenan-induced rats, the analgesic, and antipyretic activities of ESA-EO and ESA-EO-NE were evaluated in rats. Forty-three compounds were identifed via GC-MS and categorized as mono-(61.38%) and ses-quiterpenes (34.86%). d-limonene (32.82%), α-pinene (24.33%), germacrene-D (4.88%), α-humulene (4.73%), α-cadinol (3.39%), and trans-caryophyllene (3.15%) represented the main components. Te administration of ES-EO and ES-EO-NE (50 and 100 mg/kg) demonstrated strong, dose-dependent infammation inhibition capabilities in the model of rat paw edema, in comparison with both the reference drug and control. Reduced levels of malondialdehyde (MDA), increased levels of glutathione (GSH), and decreased levels of the proinfammatory cytokines (TNF-α), nitrosative (NO), and prostaglandin E2 (PGE2) in paw tissues all contributed to these substantial reductions in infammation. Moreover, the oral administration of ESA-EO and ESA-EO-NE (50 and 100 mg/kg) exhibited potent analgesic and antipyretic activities in rats. Although the higher dose of ESA-EO and ESA-EO-NE (100 mg/kg) displayed delayed anti-infammatory activity, they have long-lasting infammation inhibition with fast onset and long-standing analgesic efects better than reference drugs. Furthermore, the most efective antipyretic efcacy was provided by ESA-EO-NE (100 mg/kg). Tese results provide insight into the possible therapeutic application of ESA-EO and its nanoemulsion against various infammatory and painful illnesses as well as hy-perthermia ailments.
... It is this rationality that encourages to re-investigate ancient practices and pharmacopeias. Modern technological advances may enable to reexploit these ancient remedies more easily [76][77][78]. ...
The proliferation and prevalence of antibiotic-resistant bacteria despite modern medicine is considered as one of the most alarming threats to global health. The fear that antibiotics that work today might not work tomorrow makes it imperative to search and develop novel drugs or therapeutic strategies to fight against micro-organisms resistant to our current approaches. From many centuries, people have sought solutions to combat infections and proposed countless remedies, traces of which can be found in manuscripts preserved over the past centuries. The re-examination and exploitation of these ancient remedies might be a key to a vast pool of potential therapeutic strategies or drug candidates against antibiotic-resistant pathogens. This, however, would first require the consideration of these ancient solutions as scientifically pertinent leads for new therapies. The aim of this review is to highlight arguments in favor of a rationality in the scientific approach of these past physicians as well as of a medicinal interest in studying these ancient pharmacopeias. To narrow the scope of our research, we focused on the Arab Medieval Golden Medical Age, which inspired occidental medicine hundreds of years after its preeminence. We further highlight the possibility of integrating this knowledge into innovative, modern therapeutic approaches.
... To obtain the novel compounds with improved bioavailability and minimal side effects, extensive experiments, screening, in vitro and in vivo testing and ADMET profiling are essential. The traditional drug discovery approach required intense labor, a time-consuming multi-step process to develop novel molecules for in vivo biological screening and ADMET profiling to deliver a drug (AlQaraghuli et al. 2017). To overcome the drawbacks of the traditional drug discovery process new highly interdisciplinary approaches came into existence. ...
Polyethylene glycol (PEG) is one of the most extensively used biocompatible polymer. PEG-modification improves the original properties of conjugates and thus being exploited in different fields. PEGs demonstrated their ability to bind DNA, dyes and proteins, in solution and in solid phase via amine and thiol groups. Covalent linkage of PEG to drug molecules improves water-solubility, bioavailability, pharmacokinetics, immunogenic properties, and biological activities. Entrapment of drugs into the PEG vesicle offers substantial benefits in the treatment of many diseases including type 2 diabetes over conventional injection-based therapies. Therapeutic enzymes are conjugated with PEG for targeted therapy of diseases in which the native enzyme was inefficient. PEG has been most extensively investigated polymers for gene delivery due to its capability to form stable complexes by electrostatic interactions with nucleic acids. Many PEG-enzymes conjugates have already obtained FDA approval for clinical implications. PEGylated copolymers have least cytotoxicity and cell-compatibility concern, high efficiency, safety and biocompatibility and thus considered as an attractive polymer for gene and drug delivery system. For instance, many tissue engineering applications, PEG and its derivatives are likely to precise control of cell behaviour in growing tissues. For this application numerous bioresponsive and intelligent biomaterials are developed and extensively used in bone and tissue regeneration. PEG-derived hydrogels increase gene expression of bone-specific markers, secretion of bone-related matrix, and mineralization and may have a potential impact on bone-engineering therapies. PEG-coated poly(amidoamine) exhibits low toxicity to human corneal epithelial cells and effectively used as antimicrobial agents.
... Use of drug delivery systems Nanohybrids have been used as drug delivery systems to release drugs into a particular site in the body at a specific rate. Different drug delivery systems have been developed, including liposomes, lipid nanoemulsions and polylactide-coglycolide (PLGA) and the use of natural polymers such as collagen and chitosan (Al-Qaraghuli et al. 2017;Obeid et al. 2017a, b). Various strategies utilize liposomes and pheroids to improve the solubility and transport of antimalarial drugs to their target sites. ...
The global challenge to the treatment of malaria is mainly the occurrence of resistance of malaria parasites to conventionally used antimalarials. Artesunate, a semisynthetic artemisinin compound, and other artemisinin derivatives are currently used in combination with selected active antimalarial drugs in order to prevent or delay the emergence of resistance to artemisinin derivatives. Several methods, such as preparation of hybrid compounds, combination therapy, chemical modification and the use of synthetic materials to enhance solubility and delivery of artesunate, have been employed over the years to improve the antimalarial activity of artesunate. Each of these methods has advantages it bestows on the efficacy of artesunate. This review discussed the various methods employed in enhancing the antimalarial activity of artesunate and delaying the emergence of resistance of parasite to it.
... The relevance of natural products and medicinal plants in drug discovery and identification of active molecules has been well reviewed [1][2][3][4][5][6]. The problem today is the slow pace of discovery of new active compounds from reportedly active medicinal plant extracts [7]. ...
The absence or idle state of analytical equipment such as nuclear magnetic resonance spectroscopy, mass spectrometers and chromatographic techniques has constrained natural products research in Nigeria. Presently, gas chromatography-mass spectrometry has become the more easily available method in Nigeria for the identification of natural products in extracts. This method is sometimes fraught with non-reproducible results and the identification of non-natural or biosynthesized compounds. Several of the extracts analyzed are not volatile, some of the analysts are not competent and certified reference standards are hardly used. These coupled with poor library or database matches and data processing among others lead to the identification of compounds not recognizable from the extract or plants materials under study. This review discusses some of the problems involved in the use of this method for dereplication studies of plant extracts in Nigeria and makes some suggestions for improvement.
... For instance, drug development projects may use different technologies according to the maturity of "the underlying scientific fields, the relevant scientific theory, 1 https://www.kirinholdings.co.jp/english/company/rd/. and the availability of process engineering heuristics " ( Pisano, 1996( Pisano, , p. 1101. To illustrate, Soxhlet solvent extraction and infusion are traditional techniques used to extract constituents ( Qaraghuli, Alzahrani, Niwasabutra, Obeid, and Ferro, 2017 ). In a radical departure from this method, nanobiotechnology techniques have been found to improve the therapeutic index and provide solutions to drug delivery problems for new classes of biotech drugs ( Dinda and Pattnaik, 2013 ). ...
Firms typically manage project portfolios with specific characteristics, including lengthy and high-risk projects with many similarities in human and technological resources and whose sequence and movement through the pipeline create longitudinal interdependencies. Interdependencies increase the complexity of project portfolios and create constraints in decision-making. This paper focuses on resource interdependencies and aims deepen our understanding of the extent to which resource interdependencies affect project termination. We study a sample of 417 new biotechnology-based drug discovery and development projects initiated by 25 biopharmaceutical SMEs. To test the hypotheses, we employ survival analysis and model terminations as a conditional probability and a corresponding hazard function. Our results show that for drug development projects, only certain types of interdependencies have a significant effect.
... Therefore, therapeutic application of siRNA requires the use of an efficient delivery vehicle that can carry, protect, and efficiently deliver siRNA into target cells [3]. In this regard, lipid-based nanoparticles, including liposomes, have been widely investigated as possible siRNA carriers because of their advantages such as high loading efficiency and biocompatibility [4,5]. Through their membrane bilayer structure, lipid nanoparticles can protect siRNA that is embedded in the aqueous core or adsorbed on the surface of the nanoparticles [6]. ...
RNA interference (RNAi) is an effective and naturally occurring post-transcriptional gene regulatory mechanism. This mechanism involves the degradation of a target messenger RNA (mRNA) through the introduction of short interfering RNA (siRNA) that is complementary to the target mRNA. The application of siRNA-based therapeutics is limited by the development of an effective delivery system, as naked siRNA is unstable and cannot penetrate the cell membrane. In this study, we investigated the use of cationic niosomes (CN) prepared by microfluidic mixing for siRNA delivery. In an in vitro model, these vesicles were able to deliver anti-luciferase siRNA and effectively suppress luciferase expression in B16-F10 mouse melanoma cells. More importantly, in an in vivo mouse model, intratumoral administration of CN-carrying anti-luciferase siRNA led to significant suppression of luciferase expression compared with naked siRNA. Thus, we have established a novel and effective system for the delivery of siRNA both in vitro and in vivo, which shows high potential for future application of gene therapeutics.
... The traditional drug discovery process includes step by step process from lead discovery (duration: 3 years), preclinical development (duration: 1 year), clinical development (duration: 4 years) and Food and Drug Administration (FDA) filing (duration: 1.5 years) (Hughes et al. 2011). As can be seen from the time taken by each step, these traditional methods can be labour intensive and timeconsuming (Al Qaraghuli et al. 2017). However, the new development of computational technology can simplify and speed up the drug discovery process. ...
Drug discovery is the process through which new drugs are discovered. One of the most common techniques in drug discovery is similarity searching based on virtual screening that involves comparing the similarity between molecule structures in chemical database using established similarity methods. The objective of this study is to identify the similarity of the structure in chemical dataset using Mean Pairwise Similarity (MPS) calculation and to determine the best coefficient to be used in similarity searching which involves of molecular descriptor ECFP2 fingerprint and three types of similarity coefficient which are Tanimoto, Soergel and Euclidean. From the results, it was deduced that Tanimoto and Soergel coefficients has a better performance than Euclidean coefficient. For future work, different combinations of fingerprints such as Daylight, BCI, Unity MDL and similarity coefficient can be studied further.
... Different types of drug delivery systems can be used for this purpose including liposomes, niosomes, lipid nano-emulsions, poly(lactideco-glycolide) (PLGA), and natural polymers such as collagen and chitosan [46][47][48]. The most commonly used delivery systems for the delivery of anti-malarial agents are summarised in Table 1. ...
Malaria is an ubiquitous disease that can affect more than 40% of the world’s population who live with some risk of contracting this disease. The World Health Organization (WHO) has recently highlighted the high spread of this disease in Sub-Saharan Africa. Despite the considerable fall in mortality rate over the past decade, the development of resistance against main treatment strategies still exists. This problem has provoked scientific efforts to develop various treatment strategies including use of vaccines, drug delivery systems, and biotherapeutics approaches. A vaccination strategy is being implemented to trigger direct clearance of the causative parasites from the human host. However, the complex life-cycle of Plasmodium parasites with continuous antigenic mutations has partly hindered this approach so far. The application of different types of drug delivery systems for the delivery of anti-malarial drugs is also being considered in order to improve the efficacy, pharmacokinetics, tolerability, and reduce toxicity of existing anti-malarial drugs. A third approach has emerged from the high success of antibodies to treat complex diseases like cancer and autoimmune diseases. Various antibody engineering methods and formats have been proposed to tackle the notable sophisticated lifecycle of malaria. Within the malaria research field, the characteristics of these diverse treatment strategies, individually, are broadly acknowledged. This review article considers the current status of these approaches and the future outlook.
The drug discovery and development process is very lengthy, highly expensive, and extremely complex in nature. Considering the time and cost constraints associated with conventional drug discovery, new methods must be found to enhance the declining efficiency of traditional approaches. Artificial intelligence (AI) has emerged as a powerful tool that harnesses anthropomorphic knowledge and provides expedited solutions to complex challenges. Advancements in AI and machine learning (ML) techniques have revolutionized their applications to drug discovery and development. This review illuminates the profound influence of AI on diverse aspects of drug discovery, encompassing drug-target identification, molecular properties, compound analysis, drug development, quality assurance, and drug toxicity assessment. ML algorithms play an important role in testing systems and can predict important aspects such as the pharmacokinetics and toxicity of drug candidates. This review not only strengthens the theoretical foundation and development of this technology, but also explores the myriad challenges and promising prospects of AI in drug discovery and development. The combination of AI and drug discovery offers a promising strategy to overcome the challenges and complexities of the pharmaceutical industry.
