Publications by authors named "Abdul Basit"

387 Publications

Enhancement of resistance by poultry manure and plant hormones (salicylic acid & citric acid) against tobacco mosaic virus.

Saudi J Biol Sci 2021 Jun 17;28(6):3526-3533. Epub 2021 Mar 17.

Assiut University, Faculty of Science, Botany and Microbiology Department, Assiut 71516, Egypt.

Virus is the most menacing factor for plant, which causes enormous economic losses in agriculture worldwide. Tobacco mosaic virus is most hazardous virus among the plants that can spread through biological and non-biological sources. TMV is ancient virus that causes huge economic losses to pepper cucumber ornamental crops and tobacco. It can be controlled by reducing the population of vector through pesticide application. However, the rapid usage of synthetic chemicals causes environmental pollution and destroys our ecosystem. Consequently, different approaches just like natural derivatives should be adopted for the environmental friendly management for TMV. This in vitro study demonstrated the potential role of natural metabolites such as poultry manure and plant extracts such as salicylic acid and citric acid for the control of TMV. Two different concentrations of poultry manure 60G and 30G were used. Poultry manure was mixed with the soil at the time of sowing. Disease severity was minimum at maximum concentration as compared to the control. Meanwhile, two different concentrations of salicylic acid and citric acid 60% and 90% were applied by foliar sprayer after three-leaf stages. Disease severity was observed after 5, 10, 15, 20, 25, and 30 days after disease inoculation. Here also maximum concentration showed the minimum disease severity and higher concentration of both animal and plants extracts were used for following experiment. Quantitative real-time PCR (RT-qPCR) results demonstrated that different plant defense-related genes such as and were up-regulated. Furthermore, applications of each treatment-induced systemic resistance against a wide range of pathogen including TMV and fungal pathogen
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http://dx.doi.org/10.1016/j.sjbs.2021.03.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176140PMC
June 2021

Do microbial protein elicitors PeaT1 obtained from and PeBL1 from enhance defense response against tomato aphid ()?

Saudi J Biol Sci 2021 Jun 25;28(6):3242-3248. Epub 2021 Feb 25.

Department of Biology, Faculty of Science, Princess Nourah Bint Abdul Rehman University, Saudi Arabia.

Tomato aphid () is a destructive insect pest of tomato responsible for huge losses in the production as well in the vegetable industry. In the present in vitro study two protein elicitors, PeaT1 and PeBL1 were considered to study their efficacies to exhibit defense response against tomato aphid. Three different concentrations of both protein elicitors were applied on the tomato seedlings. After the application of PeaT1 and PeBL1, population growth rates of tomato aphid were decreased as compared to the control treatment. In host preference assay, the tomato aphid showed a preference to build a colony on the control as compared to the treated tomato plant, because tomato leaves provided hazardous surface for aphid after the formation of wax and trichome. The concentrations of protein showed significant ( < 0.05) results in life-history traits of the aphid. Jasmonic acid (JA), salicylic acid (SA) and ethylene (ET) showed significant accumulation in tomato seedlings treated with PeaT1 and PeBL1. Elicitors treated plants produced resistance against . Our finding suggests that PeaT1 and PeBL1 have shown high potentials against the damage of , and both elicitors could be used as novel biological tools against tomato aphid.
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http://dx.doi.org/10.1016/j.sjbs.2021.02.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176006PMC
June 2021

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Drug Metab Dispos 2021 Jun 1. Epub 2021 Jun 1.

Department of Pharmaceutical Sciences, Washington State University, United States

Anticancer drug, irinotecan shows serious dose-limiting gastrointestinal toxicity regardless of intravenous dosing. Although enzymes and transporters involved in irinotecan disposition are known, quantitative contributions of these mechanisms in complex in vivo disposition of irinotecan are poorly understood. We explained intestinal disposition and toxicity of irinotecan by integrating i) in vitro metabolism and transport data of rinotecan and its metabolites, ii) ex vivo gut microbial activation of the toxic metabolite, SN-38, and iii) the tissue protein abundance data of enzymes and transporters relevant to irinotecan and its metabolites. Integration of in vitro kinetics data with the tissue enzyme and transporter abundance predicted that carboxylesterase (CES) mediated hydrolysis of irinotecan is the rate-limiting process in the liver, where the toxic metabolite formed is rapidly deactivated by glucuronidation. In contrast, the poor SN-38 glucuronidation rate as compared to its efficient formation by CES2 in the enterocytes is the key mechanism of the intestinal accumulation of the toxic metabolite. The biliary efflux and OATP2B1 mediated enterocyte uptake can also synergize buildup of SN-38 in the enterocytes, whereas intestinal P-glycoprotein (P-gp) likely facilitates SN38 detoxification in the enterocytes. The higher SN-38 concentration in the intestine can be further nourished by β-d-glucuronidases. Understanding the quantitative significance of the key metabolism and transport processes of irinotecan and its metabolites can be leveraged to alleviate its intestinal side effects. Further, the proteomics-informed quantitative approach to determine intracellular disposition can be extended to determine susceptibility of cancer cells over normal cells for precision irinotecan therapy. This work provides a deeper insight into the quantitative relevance of irinotecan hydrolysis (activation), conjugation (deactivation), and deconjugation (reactivation) by human or gut microbial enzymes or transporters. The results of this study explain the characteristic intestinal exposure and toxicity of irinotecan. Quantitative tissue-specific in vitro to in vivo extrapolation approach presented in this study can be extended to cancer cells.
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http://dx.doi.org/10.1124/dmd.121.000476DOI Listing
June 2021

Inorganic Thermoelectric Fibers: A Review of Materials, Fabrication Methods, and Applications.

Sensors (Basel) 2021 May 14;21(10). Epub 2021 May 14.

School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore.

Thermoelectric technology can directly harvest the waste heat into electricity, which is a promising field of green and sustainable energy. In this aspect, flexible thermoelectrics (FTE) such as wearable fabrics, smart biosensing, and biomedical electronics offer a variety of applications. Since the nanofibers are one of the important constructions of FTE, inorganic thermoelectric fibers are focused on here due to their excellent thermoelectric performance and acceptable flexibility. Additionally, measurement and microstructure characterizations for various thermoelectric fibers (Bi-Sb-Te, AgTe, PbTe, SnSe and NaCoO) made by different fabrication methods, such as electrospinning, two-step anodization process, solution-phase deposition method, focused ion beam, and self-heated 3ω method, are detailed. This review further illustrates that some techniques, such as thermal drawing method, result in high performance of fiber-based thermoelectric properties, which can emerge in wearable devices and smart electronics in the near future.
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http://dx.doi.org/10.3390/s21103437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156617PMC
May 2021

5-Aminolevulinic Acid as a Novel Therapeutic for Inflammatory Bowel Disease.

Biomedicines 2021 May 20;9(5). Epub 2021 May 20.

Intract Pharma Limited, London Bioscience Innovation Centre, London NW1 0NH, UK.

5-Aminolevulinic acid (5-ALA) is a naturally occurring nonprotein amino acid licensed as an optical imaging agent for the treatment of gliomas. In recent years, 5-ALA has been shown to possess anti-inflammatory and immunoregulatory properties through upregulation of heme oxygenase-1 via enhancement of porphyrin, indicating that it may be beneficial for the treatment of inflammatory conditions. This study systematically examines 5-ALA for use in inflammatory bowel disease (IBD). Firstly, the ex vivo colonic stability and permeability of 5-ALA was assessed using human and mouse fluid and tissue. Secondly, the in vivo efficacy of 5-ALA, in the presence of sodium ferrous citrate, was investigated via the oral and intracolonic route in an acute DSS colitis mouse model of IBD. Results showed that 5-ALA was stable in mouse and human colon fluid, as well as in colon tissue. 5-ALA showed more tissue restricted pharmacokinetics when exposed to human colonic tissue. In vivo dosing demonstrated significantly improved colonic inflammation, increased local heme oxygenase-1 levels, and decreased concentrations of proinflammatory cytokines TNF-α, IL-6, and IL-1β in both plasma and colonic tissue. These effects were superior to that measured concurrently with established anti-inflammatory treatments, ciclosporin and 5-aminosalicylic acid (mesalazine). As such, 5-ALA represents a promising addition to the IBD armamentarium, with potential for targeted colonic delivery.
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http://dx.doi.org/10.3390/biomedicines9050578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160866PMC
May 2021

Mutation-Based Antibiotic Resistance Mechanism in Methicillin-Resistant Clinical Isolates.

Pharmaceuticals (Basel) 2021 May 1;14(5). Epub 2021 May 1.

National Leading Research Laboratory, Department of Biological Sciences, Myongji University, 116 Myongjiro, Yongin, Gyeonggido 17058, Korea.

β-Lactam antibiotics target penicillin-binding proteins and inhibit the synthesis of peptidoglycan, a crucial step in cell wall biosynthesis. acquires resistance against β-lactam antibiotics by producing a penicillin-binding protein 2a (PBP2a), encoded by the gene. PBP2a participates in peptidoglycan biosynthesis and exhibits a poor affinity towards β-lactam antibiotics. The current study was performed to determine the diversity and the role of missense mutations of PBP2a in the antibiotic resistance mechanism. The methicillin-resistant (MRSA) isolates from clinical samples were identified using phenotypic and genotypic techniques. The highest frequency (60%, 18 out of 30) of MRSA was observed in wound specimens. Sequence variation analysis of the gene showed four amino acid substitutions (i.e., E239K, E239R, G246E, and E447K). The E239R mutation was found to be novel. The protein-ligand docking results showed that the E239R mutation in the allosteric site of PBP2a induces conformational changes in the active site and, thus, hinders its interaction with cefoxitin. Therefore, the present report indicates that mutation in the allosteric site of PBP2a provides a more closed active site conformation than wide-type PBP2a and then causes the high-level resistance to cefoxitin.
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http://dx.doi.org/10.3390/ph14050420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147353PMC
May 2021

Optical biosensors - Illuminating the path to personalized drug dosing.

Biosens Bioelectron 2021 Sep 13;188:113331. Epub 2021 May 13.

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, United Kingdom. Electronic address:

Optical biosensors are low-cost, sensitive and portable devices that are poised to revolutionize the medical industry. Healthcare monitoring has already been transformed by such devices, with notable recent applications including heart rate monitoring in smartwatches and COVID-19 lateral flow diagnostic test kits. The commercial success and impact of existing optical sensors has galvanized research in expanding its application in numerous disciplines. Drug detection and monitoring seeks to benefit from the fast-approaching wave of optical biosensors, with diverse applications ranging from illicit drug testing, clinical trials, monitoring in advanced drug delivery systems and personalized drug dosing. The latter has the potential to significantly improve patients' lives by minimizing toxicity and maximizing efficacy. To achieve this, the patient's serum drug levels must be frequently measured. Yet, the current method of obtaining such information, namely therapeutic drug monitoring (TDM), is not routinely practiced as it is invasive, expensive, time-consuming and skilled labor-intensive. Certainly, optical sensors possess the capabilities to challenge this convention. This review explores the current state of optical biosensors in personalized dosing with special emphasis on TDM, and provides an appraisal on recent strategies. The strengths and challenges of optical biosensors are critically evaluated, before concluding with perspectives on the future direction of these sensors.
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http://dx.doi.org/10.1016/j.bios.2021.113331DOI Listing
September 2021

Harnessing Artificial Intelligence for the Next Generation of 3D Printed Medicines.

Adv Drug Deliv Rev 2021 May 18. Epub 2021 May 18.

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; FabRx Ltd., 3 Romney Road, Ashford, Kent, TN24 0RW, UK. Electronic address:

Artificial intelligence (AI) is redefining how we exist in the world. In almost every sector of society, AI is performing tasks with super-human speed and intellect; from the prediction of stock market trends to driverless vehicles, diagnosis of disease, and robotic surgery. Despite this growing success, the pharmaceutical field is yet to truly harness AI. Development and manufacture of medicines remains largely in a 'one size fits all' paradigm, in which mass-produced, identical formulations are expected to meet individual patient needs. Recently, 3D printing (3DP) has illuminated a path for on-demand production of fully customisable medicines. Due to its flexibility, pharmaceutical 3DP presents innumerable options during formulation development that generally require expert navigation. Leveraging AI within pharmaceutical 3DP removes the need for human expertise, as optimal process parameters can be accurately predicted by machine learning. AI can also be incorporated into a pharmaceutical 3DP 'Internet of Things', moving the personalised production of medicines into an intelligent, streamlined, and autonomous pipeline. Supportive infrastructure, such as The Cloud and blockchain, will also play a vital role. Crucially, these technologies will expedite the use of pharmaceutical 3DP in clinical settings and drive the global movement towards personalised medicine and Industry 4.0.
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http://dx.doi.org/10.1016/j.addr.2021.05.015DOI Listing
May 2021

Let's Talk About Sex: Differences in Drug Therapy in Males and Females.

Adv Drug Deliv Rev 2021 May 17. Epub 2021 May 17.

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29 - 39 Brunswick Square, London, WC1N 1AX, United Kingdom. Electronic address:

Professor Henry Higgins in My Fair Lady said, 'Why can't a woman be more like a man?'. Perhaps unintended, such narration extends to the reality of current drug development. A clear sex-gap exists in pharmaceutical research spanning from preclinical studies, clinical trials to post-marketing surveillance with a bias towards males. Consequently, women experience adverse drug reactions from approved drug products more often than men. Distinct differences in pharmaceutical response across drug classes and the lack of understanding of disease pathophysiology also exists between the sexes, often leading to suboptimal drug therapy in women. This review explores the influence of sex as a biological variable in drug delivery, pharmacokinetic response and overall efficacy in the context of pharmaceutical research and practice in the clinic. Prospective recommendations are provided to guide researchers towards the consideration of sex differences in methodologies and analyses. The promotion of disaggregating data according to sex to strengthen scientific rigour, encouraging innovation through the personalisation of medicines and adopting machine learning algorithms is vital for optimised drug development in the sexes and population health equity.
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http://dx.doi.org/10.1016/j.addr.2021.05.014DOI Listing
May 2021

Translating 3D printed pharmaceuticals: From hype to real-world clinical applications.

Adv Drug Deliv Rev 2021 Jul 20;174:553-575. Epub 2021 May 20.

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; FabRx Ltd., 3 Romney Road, Ashford, Kent TN24 0RW, UK; Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma Group (GI-1645), Facultad de Farmacia, and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain. Electronic address:

Three-dimensional (3D) printing is a revolutionary technology that is disrupting pharmaceutical development by enabling the production of personalised printlets (3D printed drug products) on demand. By creating small batches of dose flexible medicines, this versatile technology offers significant advantages for clinical practice and drug development, namely the ability to personalise medicines to individual patient needs, as well as expedite drug development timelines within preclinical studies through to first-in-human (FIH) and Phase I/II clinical trials. Despite the widely demonstrated benefits of 3D printing pharmaceuticals, the clinical potential of the technology is yet to be realised. In this timely review, we provide an overview of the latest cutting-edge investigations in 3D printing pharmaceuticals in the pre-clinical and clinical arena and offer a forward-looking approach towards strategies to further aid the translation of 3D printing into the clinic.
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http://dx.doi.org/10.1016/j.addr.2021.05.003DOI Listing
July 2021

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Drug Metab Dispos 2021 May 5. Epub 2021 May 5.

Department of Pharmaceutical Sciences, Washington State University, United States

The increasing incidence of ocular diseases has accelerated research into therapeutic interventions needed for the eye. Ocular enzymes play important roles in the metabolism of drugs and endobiotics. Various ocular drugs are designed as prodrugs that are activated by ocular enzymes. Moreover, ocular enzymes have been implicated in the bioactivation of drugs to their toxic metabolites. The key purpose of this study was to compare global proteomes of the pooled samples of the eye (n=11) and the liver (n=50), with a detailed analysis of the abundance of enzymes involved in the metabolism of xenobiotics and endobiotics. We used the post-mitochondrial supernatant fraction (S9 fraction) of the lens-free whole eye homogenate as a model to allow accurate comparison with the liver S9 fraction. A total of 269 proteins (including 23 metabolic enzymes) were detected exclusively in the pooled eye S9, against 648 proteins in the liver S9 (including 174 metabolic enzymes), whereas 424 proteins (including 94 metabolic enzymes) were detected in both the organs. The major hepatic cytochrome P450 and UDP-glucuronosyltransferases enzymes were not detected, but aldehyde dehydrogenases and glutathione transferases were the predominant proteins in the eye. The comparative qualitative and quantitative proteomics data in the eye versus liver is expected to help in explaining differential metabolic and physiological activities in the eye. Information on the enzymes involved in xenobiotic and endobiotic metabolism in the human eye in relation to the liver is scarcely available. We employed global proteomic analysis to compare the proteomes of the lens-free whole eye and the liver with a detailed analysis of the enzymes involved in xenobiotic and endobiotic metabolism. These data will help in better understanding of the ocular metabolism and activation of drugs and endobiotics.
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http://dx.doi.org/10.1124/dmd.120.000297DOI Listing
May 2021

Advances in powder bed fusion 3D printing in drug delivery and healthcare.

Adv Drug Deliv Rev 2021 Jul 2;174:406-424. Epub 2021 May 2.

UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; FabRx Ltd., Henwood House, Henwood, Ashford, Kent TN24 8DH, UK. Electronic address:

Powder bed fusion (PBF) is a 3D printing method that selectively consolidates powders into 3D objects using a power source. PBF has various derivatives; selective laser sintering/melting, direct metal laser sintering, electron beam melting and multi-jet fusion. These technologies provide a multitude of benefits that make them well suited for the fabrication of bespoke drug-laden formulations, devices and implants. This includes their superior printing resolution and speed, and ability to produce objects without the need for secondary supports, enabling them to precisely create complex products. Herein, this review article outlines the unique applications of PBF 3D printing, including the main principles underpinning its technologies and highlighting their novel pharmaceutical and biomedical applications. The challenges and shortcomings are also considered, emphasising on their effects on the 3D printed products, whilst providing a forward-thinking view.
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http://dx.doi.org/10.1016/j.addr.2021.04.025DOI Listing
July 2021

Characterization of a lytic EBP bacteriophage with large size genome against Enterobacter cloacae.

APMIS 2021 May 5. Epub 2021 May 5.

Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan, 54590, Pakistan.

Enterobacter cloacae (E. cloacae) is an emerging nosocomial pathogen that had acquired antibiotic resistance against multiple classes of antibiotics. The current study was aimed to isolate and characterize lytic bacteriophage against E. cloacae. The bacteriophage EBP was isolated from a sewage water sample using E. cloacae as a host strain by double-layer agar technique. EBP was found stabile at a wide range of temperatures (25, 37, 60, and 80°C) and pH (5, 6, 7, 8, and 9) with antibacterial activity up to 24 h of infection. The latent period of EBP was 20 min with a burst size of 252 phages per cell. It showed a narrow host range and infected 12/21 (57%) isolates of E. cloacae tested. It has helical symmetry with a head size of 105 and 120 nm long tail with contractile sheath. The EBP has 179.1 kb long double-stranded DNA genome with 44.8% GC content. Majority of identified ORFs (187/281) were encoding putative proteins with unknown function. Necessary replication enzymes, structural proteins, and lytic enzymes were detected in the genome of EBP. Phylogenetic analysis revealed that EBP closely resembles with Coronobacter phage vB_CsaM_IeN, vB_CsaM_IeE, vB_CsaM_IeB, and Citrobacter phage Margaery. Based on electron microscopy and molecular characterization, EBP was classified as a Myoviridae phage.
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http://dx.doi.org/10.1111/apm.13138DOI Listing
May 2021

Knowledge scores in annual and modular curriculum among medical students from Karachi, Pakistan.

J Pak Med Assoc 2021 Feb;71(2(B)):681-685

Liaquat National Medical College and Hospital, Karachi, Pakistan.

Objective: To compare the knowledge scores of basic medical subjects in annual versus modular system among undergraduate medical students.

Methods: A cross-sectional survey was conducted on 4th year undergraduate medical students of annual and modular system of Liaquat National Medical College, Pakistan. Study was conducted from 30th November 2017 to 1st June 2018 for a total of 6 months. Sample size was calculated to be 82 students. The data was collected using a structured questionnaire. The student's t-test was applied to compare the mean difference of knowledge scores between the two groups.

Results: Students in modular system retained better knowledge of anatomy as compared to annual students. However, the annual system students retained higher knowledge in subjects of community medicine and pharmacology. Mean knowledge score among students for annual system was 12.98 ± 2.92 and semester system was 13.1 ± 3.03. There was no significant difference observed in overall mean knowledge scores between the two groups (p=0.85).

Conclusions: Students in the annual system scored higher in pharmacology and community medicine. This highlighted the need to address the issues of time allocation and implementation strategies for the subjects in the new system. There was no difference between overall knowledge scores in each group, hence, it would be inappropriate to conclude that one system is superior to the other.
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http://dx.doi.org/10.47391/JPMA.1416DOI Listing
February 2021

Analyzing the Underlying Structure of Online Teaching During the COVID-19 Pandemic Period: An Empirical Investigation of Issues of Students.

Front Psychol 2021 15;12:605138. Epub 2021 Apr 15.

Lahore Institute of Science and Technology, Lahore, Pakistan.

The aim of the study is to reveal the underlying structure of issues of university students taking online classes during the COVID-19 pandemic period. The overall design of the study includes a review of contemporary literature and field survey for data collection and analysis. Discourse of literature coupled with expert opinion has been employed for identification of issues. Interpretive Structural Modeling (ISM) is used for the determination of intra-issue relationships and analyzing the underlying structure. Cross impact matrix multiplication applied to classification (MICMAC analysis) is used as a technique for classifying issues on the basis of driving-dependence power. Results of the literature show that there are 21 major issues faced by the students taking online classes. ISM shows that lack of institutional guidelines, lack of regulators' guidelines, stress of pandemic situation, and abrupt (not planned) start of online classes are the most critical issues. MICMAC analysis reveals that there is no autonomous issue, 4 (i.e., connectivity issue, shy to use technology, lack of institutional guidelines, and stress of pandemic situation) are independent, 6 other issues are dependent, and the remaining 11 are linking. This is a valuable study having practical implications for regulators, students, parents, and society to understand the current problem. It is an original attempt that contributes toward literature in the form of a structural model and a diagram of classification of issues.
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http://dx.doi.org/10.3389/fpsyg.2021.605138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084101PMC
April 2021

USH2A gene variants cause Keratoconus and Usher syndrome phenotypes in Pakistani families.

BMC Ophthalmol 2021 Apr 29;21(1):191. Epub 2021 Apr 29.

Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, 26000, Khyber Pakhtunkhwa, Pakistan.

Background: Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy, affecting approximately 1 in 4000 individuals worldwide. The most common form of syndromic RP is Usher syndrome (USH) accounting for approximately 20-30 % of RP cases. Mutations in the USH2A gene cause a significant proportion of recessive non-syndromic RP and USH type II (USH2). This study aimed to determine the causative role of the USH2A gene in autosomal recessive inherited ocular diseases and to establish genotype-phenotype correlation associated with USH2A variants.

Methods: We performed direct Sanger sequencing and co-segregation analysis of the USH2A gene to identify disease causing variants in a non-syndromic RP family, two USH2 families and two Keratoconus (KC) families.

Results: Disease causing variants in the USH2A gene were identified in two families displayed KC and USH2 phenotypes. A novel variant c.4029T > G, p.Asn1343Lys in the USH2A gene was detected in a Pakistani family with KC phenotype. In addition, a missense variant (c.7334 C > T, p. Ser2445Phe) in the USH2A gene was found segregating in another Pakistani family with USH2 phenotype. Homozygosity of identified missense USH2A variants was found associated with autosomal recessive inherited KC and USH2 phenotypes in investigated families. These variants were not detected in ethnically matched healthy controls. Moreover, the USH2A variants were predicted to be deleterious or potentially disease causing by PolyPhen-2, PROVEAN and SIFT.

Conclusions: This study provided first evidence for association of a novel USH2A variant with KC phenotype in a Pakistani family as well as established the phenotype-genotype correlation of a USH2A variant (c.7334 C > T, p. Ser2445Phe) with USH2 phenotype in another Pakistani family. The phenotype-genotype correlations established in present study may improve clinical diagnosis of affected individuals for better management and counseling.
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http://dx.doi.org/10.1186/s12886-021-01957-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086330PMC
April 2021

Effect of host plant on cornucopia of mango fruit flies (Diptera: Tephritidae) and their triumphant management in context of climate change.

Saudi J Biol Sci 2021 Apr 19;28(4):2366-2373. Epub 2021 Feb 19.

Department Soil & Environmental Sciences, Muhammad Nawaz Sharif University of Agriculture Multan, Pakistan.

A study was performed to assess the preference of fourteen mango cultivars for fruit flies and their management by bagging. So the choice of Tephritid flies to mango cultivars during fruiting phase is crucial. Fourteen different cultivars of mango viz., 'Dusehri', 'Malda', 'Langra' early cultivars, 'Chaunsa', 'Fajri Klan', 'Sensation' medium whereas 'Sanglakhi', 'Retaul-12', 'Mehmood Khan', 'Tukhmi', 'Kala Chaunsa', 'Chitta Chaunsa', 'Dai Wala' and 'Sobey De Ting' late cultivars were assessed for their suitability for fruit flies. The results indicate that the population density of fruit flies was higher on late cultivars like 'Sanglakhi' (20.61 percent), 'Mehmood Khan' (20.22 percent) and 'Reutal-12' (19.92 percent) were proved to be highly susceptible to fruit flies. Among these the cultivar 'Reutal-12' was selected being commercial and future cultivar for the management of fruit flies through bagging. The results reported that the attack of tephritid fruit flies and other insect pests were zero in bagged fruits as compared with control. It was further recorded that the bagged fruits has maximum average fruit weight i.e. 203.50 and 197.83 g per fruit was noted in those treatments where butter paper bag and brown paper bag was wrapped with better coloration as compared with un-bagged fruit with 159.5 g per fruit. Similarly, on an average fruit length were more i.e. 90.17, 91.33 mm in bagged fruit and 85.33 in un-bagged fruits. Furthermore, bagged fruits have zero incidence of disease with reduced fruit crack, fruit sunburn, mechanical damage, bird damage, fruit blemished and agrochemical residues on the fruit. So, it is concluded that the special attention should be given on 'Reutal-12' for the management of fruit flies when devising an IPM program for the control of fruit flies. Further, bagging has proved to be the good agricultural practices for the production of quality mango.
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http://dx.doi.org/10.1016/j.sjbs.2021.01.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071905PMC
April 2021

Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3.

Sci Transl Med 2021 Apr;13(591)

Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA.

Acute lung injury (ALI) causes high mortality and lacks any pharmacological intervention. Here, we found that pazopanib ameliorated ALI manifestations and reduced mortality in mouse ALI models and reduced edema in human lung transplantation recipients. Pazopanib inhibits mitogen-activated protein kinase kinase kinase 2 (MAP3K2)- and MAP3K3-mediated phosphorylation of NADPH oxidase 2 subunit p47 at Ser to increase reactive oxygen species (ROS) formation in myeloid cells. Genetic inactivation of MAP3K2 and MAP3K3 in myeloid cells or hematopoietic mutation of p47 Ser to alanine attenuated ALI manifestations and abrogates anti-ALI effects of pazopanib. This myeloid MAP3K2/MAP3K3-p47 pathway acted via paracrine HO to enhance pulmonary vasculature integrity and promote lung epithelial cell survival and proliferation, leading to increased pulmonary barrier function and resistance to ALI. Thus, pazopanib has the potential to be effective for treating ALI.
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http://dx.doi.org/10.1126/scitranslmed.abc2499DOI Listing
April 2021

Race/ethnicity and challenges for optimal insulin therapy.

Diabetes Res Clin Pract 2021 Apr 20;175:108823. Epub 2021 Apr 20.

Faculty of Medicine, Federal University of Ceará (FAMED-UFC), Fortaleza-Ceará, Brazil; International Diabetes Federation, IDF, Brussels, Belgium; Centre for Global Health Research, Diabetic Association of Bangladesh, Dhaka, Bangladesh; Faculty of Health Sciences, Nord University, Bodø, Norway. Electronic address:

Aims: We aimed to review insulin dosing recommendations, insulin regulation and its determinants, glycaemic response to carbohydrates, and the efficacy and safety of insulin therapy in different races/ethnicities.

Methods: We searched for articles in PubMed and Google Scholar databases up to 31 March 2021, with the following keywords: "ethnicity", "diabetes", "insulin", "history of insulin", "insulin therapy", "food/rice", "carbohydrate intake", "insulin resistance", "BMI", "insulin dosing", "insulin sensitivity", "insulin response", "glycaemic index", "glycaemic response", "efficacy and safety", with interposition of the Boolean operator "AND".In addition, we reviewed the reference lists of the articles found.

Results: The differential effect of race/ethnicity has not yet been considered in current insulin therapy guidelines. Nevertheless, body size and composition, body mass index, fat distribution, diet, storage, and energy expenditure vary significantly across populations. Further, insulin sensitivity, insulin response, and glycaemicresponse to carbohydrates differ by ethnicity. These disparities may lead to different insulin requirements, adversely impacting the efficacy and safety of insulin therapy among ethnic groups.

Conclusions: Race/ethnicity affects glucose metabolism and insulin regulation.Until now, international guidelines addressing racial/ethnic-specific clinical recommendations are limited. Comprehensive updated insulin therapy guidelines by ethnicity are urgently needed.
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http://dx.doi.org/10.1016/j.diabres.2021.108823DOI Listing
April 2021

Quantification of P-Glycoprotein in the Gastrointestinal Tract of Humans and Rodents: Methodology, Gut Region, Sex, and Species Matter.

Mol Pharm 2021 05 22;18(5):1895-1904. Epub 2021 Apr 22.

UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, U.K.

Intestinal efflux transporters affect the gastrointestinal processing of many drugs but further data on their intestinal expression levels are required. Relative mRNA expression and relative and absolute protein expression data of transporters are commonly measured by real-time polymerase chain reaction (RT-PCR), Western blot and mass spectrometry-based targeted proteomics techniques. All of these methods, however, have their own strengths and limitations, and therefore, validation for optimized quantification methods is needed. As such, the identification of the most appropriate technique is necessary to effectively translate preclinical findings to first-in-human trials. In this study, the mRNA expression and protein levels of the efflux transporter P-glycoprotein (P-gp) in jejunal and ileal epithelia of 30 male and female human subjects, and the duodenal, jejunal, ileal and colonic tissues in 48 Wistar rats were quantified using RT-PCR, Western blot and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A similar sex difference was observed in the expression of small intestinal P-gp in humans and Wistar rats where P-gp was higher in males than females with an increasing trend from the proximal to the distal parts in both species. A strong positive linear correlation was determined between the Western blot data and LC-MS/MS data in the small intestine of humans ( = 0.85). Conflicting results, however, were shown in rat small intestinal and colonic P-gp expression between the techniques ( = 0.29 and 0.05, respectively). In RT-PCR and Western blot, an internal reference protein is experimentally required; here, beta-actin was used which is innately variable along the intestinal tract. Quantification via LC-MS/MS can provide data on P-gp expression without the need for an internal reference protein and consequently, can give higher confidence on the expression levels of P-gp along the intestinal tract. Overall, these findings highlight similar trends between the species and suggest that the Wistar rat is an appropriate preclinical animal model to predict the oral drug absorption of P-gp substrates in the human small intestine.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00574DOI Listing
May 2021

Glucagon-like peptide 1 and its association with dipeptidyl peptidase IV in subjects with various degrees of glucose tolerance.

Pak J Pharm Sci 2020 Nov;33(6(Supplementary)):2773-2778

Baqai Institute of Diabetology and Endocrinology, Karachi, Pakistan.

Dipeptidyl peptidase IV (DPP-4) and Glucagon like peptide 1 (GLP-1) has profound effect on insulin and glucagon secretion; ultimately decreasing glucose levels. We find out the association of GLP-1 levels and DPP-4 in normal, impaired and newly diagnose type 2 diabetic glucose tolerance. Prospective case control study was conducted at Department of Physiology, Baqai Medical University by the collaboration of Baqai Institute of Diabetology and Endocrinology; Karachi-Pakistan. Study groups were categorized into three groups Control, Impaired glucose tolerant (IGT) and newly diagnose type 2 diabetes mellitus (NDD). Biochemical parameters were estimated by international standard protocols. Logistic regression analysis and Chi square test with statistical significance at p value <0.05 were applied. DPP-4 concentrations were significantly lower in NDD participants compared to control and IGT participants (p=0.01), whereas GLP-1 levels were significantly higher in Control than Impaired glucose tolerant and NDD (p = 0.013). GLP1 levels and SBP were also found to be positively correlated with serum DPP4 levels in NDD group (p<0.05). GLP1 and DPP4 levels in NDD group (p<0.05) and in controls (p<0.001) respectively showed strong significant positive correlation. Effective correlation between GLP1 and DPP4 was found as both contribute to control hyperglycemia in NDD and impaired glucose tolerant people.
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November 2020

Hematological and toxicological effects of aqueous leaf extract of Stevia rebaudiana Bertoni in normal rat modals.

Pak J Pharm Sci 2020 Sep;33(5(Supplementary)):2249-2255

National Institute of food Science and Technology, University of Agriculture, Faisalabad, Pakistan.

Stevia rebaudiana Bertoni a non-caloric, safe and natural sweetener has been shown pharmaceutically important in the management of blood disorders. This study was designed to investigate hematology and safety of stevia aqueous extract through animal modeling. For this purpose, fifty albino rats were categorized into 5 groups and all the groups were received aqueous stevia extract at different dosage levels (200, 300, 400 and 500 ppm/kg b. wt) for 8 weeks except control group. Hematological and toxicological analyses were conducted using standard recommended procedures. The results indicated that biochemical parameters (RBC, HB, HCT, MCV, MCH, MCHC, WBC, eosinophils, lymphocytes and neutrophils) of albino rats significantly (P<0.05) increased and PLT, MPV and monocytes levels non-significantly decreased by using aqueous extract of stevia at different levels after eight weeks of study. Furthermore, Stevia aqueous extracts had non-toxic effect on liver functioning tests. However, stevia aqueous extracts were insignificant in their impression regarding organ to body weight ratios. The stevia aqueous extract has positive effect on hematological parameters of albino rats and is toxicologically safe. Therefore it could be used as a natural remedy for the management of hematological disorders without any health hazards.
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September 2020

Psychometric Analysis for fear of COVID-19 Scale (FCV-19S) and its association with depression in patients with diabetes: A cross sectional study from a Tertiary Care Centre in Karachi, Pakistan.

Diabetes Metab Syndr 2021 May-Jun;15(3):733-737. Epub 2021 Mar 18.

Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan. Electronic address:

Background And Aims: To assess the psychometric properties of the Fear of COVID-19 (FCV-19S) scale and to determine its associated factors among the Pakistani patients with diabetes.

Methods: This observational study was conducted in 24-h helpline service, a department of Baqai Institute of Diabetology and Endocrinology (BIDE). Study duration was from August to September 2020. The target population was registered adult patients with type 2 diabetes aged >16 years. Baseline demographic details were obtained from hospital management system of BIDE. Forward-backward translation method was used to translate the existing Fear scale (FCV-19S). Symptoms of depressive disorder were assessed through Patient Health Questionnaire (PHQ9).

Results: Total of 380 participants with mean age 51.93 ± 12.03 years contributed in the study. Three factors loading and item correlation of fear COVID-19 explained 96% of total variance having unidimensional Cronbach's alpha of 0.881. All demographic indicators that showed significance in univariate model were included in multivariate model. Females had more fear for COVID-19 compared to males (OR = 1.73, 95% CI (1.15-2.6)), whereas current smokers had also showed 4 times more fear than non-smokers (OR = 4.19, 95% CI (1.18-14.83). Depression assessed by PHQ9 showed maximum fear of COVID-19 in participants with moderate depression.

Conclusion: FCV-19S had adequate psychometric properties for assessing effects of pandemic in people with diabetes attending tertiary care center.
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http://dx.doi.org/10.1016/j.dsx.2021.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969844PMC
March 2021

Green Synthesis of Nickel Oxide Nanoparticles from Stem for Investigating Bioactivities.

Molecules 2021 Mar 11;26(6). Epub 2021 Mar 11.

Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.

Green synthesis of nanomaterials is advancing due to its ease of synthesis, inexpensiveness, nontoxicity and renewability. In the present study, an eco-friendly biogenic method was developed for the green synthesis of nickel oxide nanoparticles (NiONPs) using phytochemically rich stem (BBS) extract. The BBS extract was rich in phenolics, flavonoids and berberine. These phytochemicals successfully reduced and stabilised the NiNO (green) into NiONPs (greenish-gray). BBS-NiONPs were confirmed by using UV-visible spectroscopy (peak at 305 nm), X-ray diffraction (size of 31.44 nm), Fourier transform infrared spectroscopy (identified -OH group and Ni-O formation), energy dispersive spectroscopy (showed specified elemental nature) and scanning electron microscopy (showed rhombohedral agglomerated shape). BBS-NiONPs were exposed to multiple in vitro bioactivities to ascertain their beneficial biological applications. They exhibited strong antioxidant activities: total antioxidant capacity (64.77%) and 2, 2-diphenyl-1-picrylhydrazyl (71.48%); and cytotoxic potential: Brine shrimp cytotoxicity assay with IC (10.40 µg/mL). BBS-NiONPs restricted the bacterial and fungal pathogenic growths at 1000, 500 and 100 µg/mL. Additionally, BBS-NiONPs showed stimulatory efficacy by enhancing seed germination rate and seedling growth at 31.25 and 62.5 µg/mL. In aggregate, BBS extract has a potent antioxidant activity which makes the green biosynthesis of NiONPs easy, economical and safe. The biochemical potential of BBS-NiONPs can be useful in various biomedical and agricultural fields.
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http://dx.doi.org/10.3390/molecules26061548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999609PMC
March 2021

Ultrasensitive quantification of drug-metabolizing enzymes and transporters in small sample volume by microflow LC-MS/MS.

J Pharm Sci 2021 Mar 28. Epub 2021 Mar 28.

Department of Pharmaceutical Sciences, Washington State University, 12 E Spokane Falls Blvd, Spokane, WA 99202, USA. Electronic address:

Protein abundance data of drug-metabolizing enzymes and transporters (DMETs) are broadly applicable to the characterization of in vitro and in vivo models, in vitro to in vivo extrapolation (IVIVE), and interindividual variability prediction. However, the emerging need of DMET quantification in small sample volumes such as organ-on a chip effluent, organoids, and biopsies requires ultrasensitive protein quantification methods. We present an ultrasensitive method that relies on an optimized sample preparation approach involving acetone precipitation coupled with a microflow-based liquid chromatography-tandem mass spectrometry (µLC-MS/MS) for the DMET quantification using limited sample volume or protein concentration, i.e., liver tissues (1-100 mg), hepatocyte counts (~4000 to 1 million cells), and microsomal protein concentration (0.01-1 mg/ml). The method was applied to quantify DMETs in differential tissue S9 fractions (liver, intestine, kidney, lung, and heart) and cryopreserved human intestinal mucosa (i.e., CHIM). The method successfully quantified >75% of the target DMETs in the trypsin digests of 1 mg tissue homogenate, 15,000 hepatocytes, and 0.06 mg/ml microsomal protein concentration. The precision of DMET quantification measured as the coefficient of variation across different tissue weights, cell counts, or microsomal protein concentration was within 30%. The method confirmed significant extrahepatic abundance of non-cytochrome P450 enzymes such as dihydropyridine dehydrogenase (DPYD), epoxide hydrolases (EPXs), arylacetamide deacetylase (AADAC), paraoxonases (PONs), and glutathione S-transferases (GSTs). The ultrasensitive method developed here is applicable to characterize emerging miniaturized in vitro models and small volume biopsies. In addition, the differential tissue abundance data of the understudied DMETs will be important for physiologically-based pharmacokinetic (PBPK) modeling of drugs.
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http://dx.doi.org/10.1016/j.xphs.2021.03.020DOI Listing
March 2021

Impact of gastrointestinal tract variability on oral drug absorption and pharmacokinetics: An UNGAP review.

Eur J Pharm Sci 2021 Jul 20;162:105812. Epub 2021 Mar 20.

Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; Chairperson of the UNGAP network, COST CA 16205. Electronic address:

The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. The source of variability can be traced back to interindividual variability in physiology, differences in special populations (age- and disease-dependent), drug and formulation properties, or food-drug interactions. Clinical evidence for the impact of some of these factors on drug pharmacokinetic variability is mounting: e.g. gastric pH and emptying time, small intestinal fluid properties, differences in pediatrics and the elderly, and surgical changes in gastrointestinal anatomy. However, the link of colonic factors variability (transit time, fluid composition, microbiome), sex differences (male vs. female) and gut-related diseases (chronic constipation, anorexia and cachexia) to drug absorption variability has not been firmly established yet. At the same time, a way to decrease oral drug pharmacokinetic variability is provided by the pharmaceutical industry: clinical evidence suggests that formulation approaches employed during drug development can decrease the variability in oral exposure. This review outlines the main drivers of oral drug exposure variability and potential approaches to overcome them, while highlighting existing knowledge gaps and guiding future studies in this area.
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http://dx.doi.org/10.1016/j.ejps.2021.105812DOI Listing
July 2021

Predicting the risk of type 2 diabetes through anthropometric indices in Pakistani adults- A sub-analysis of second National diabetes survey of Pakistan 2016-2017 (NDSP-07).

Diabetes Metab Syndr 2021 Mar-Apr;15(2):543-547. Epub 2021 Feb 27.

Department of Research, Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan; Department of Biochemistry, Baqai Medical University, Karachi, Sindh, Pakistan. Electronic address:

Background And Aim: Excess adiposity is associated with an increased risk of diabetes. Amongst the various measures of adiposity, the most appropriate one to predict the risk of diabetes remains debatable. Therefore, the aim of this study was to compare the ability of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in predicting type 2 diabetes mellitus (DM) among Pakistani adults.

Subjects And Methods: This was the sub-analysis of a large population based Second National Diabetes Survey of Pakistan (NDSP) 2016-2017. With this survey, 10834 individuals were recruited and 4788 individuals fulfilled the inclusion criteria for this sub-analysis (subjects with missing anthropometric details were excluded). Participants were categorized into two groups; subjects with type 2 DM and subjects without DM. Data of participants was collected via pre-designed detailed questionnaire. Clinical and anthropometric measurements were measured using standardized techniques.

Results: Out of 4788 individuals, 3085(64.4%) were non-DM subjects and 1703(35.6%) were type 2 DM subjects with mean age of 39.78 ± 13.79 and 50.38 ± 11.33 years, respectively. Logistic regression analysis revealed a significant association of WC with type 2 diabetes after adjustment for possible confounders. Area under the curve (AUC) of WC was found higher than AUC of BMI and WHR.

Conclusion: The findings from second NDSP (2016-2017) demonstrated that WC is a better marker than WHR and BMI in predicting type 2 DM for Pakistani population.
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http://dx.doi.org/10.1016/j.dsx.2021.02.030DOI Listing
February 2021

Semi-solid extrusion 3D printing in drug delivery and biomedicine: Personalised solutions for healthcare challenges.

J Control Release 2021 Apr 27;332:367-389. Epub 2021 Feb 27.

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, I+D Farma Group (GI-1645), Universidade de Santiago de Compostela, 15782, Spain; FabRx Ltd., 3 Romney Road, Ashford, Kent TN24 0RW, UK. Electronic address:

Three-dimensional (3D) printing is an innovative additive manufacturing technology, capable of fabricating unique structures in a layer-by-layer manner. Semi-solid extrusion (SSE) is a subset of material extrusion 3D printing, and through the sequential deposition of layers of gel or paste creates objects of any desired size and shape. In comparison to other extrusion-based technologies, SSE 3D printing employs low printing temperatures which makes it suitable for drug delivery and biomedical applications, and the use of disposable syringes provides benefits in meeting critical quality requirements for pharmaceutical use. Besides pharmaceutical manufacturing, SSE 3D printing has attracted increasing attention in the field of bioelectronics, particularly in the manufacture of biosensors capable of measuring physiological parameters or as a means to trigger drug release from medical devices. This review begins by highlighting the major printing process parameters and material properties that influence the feasibility of transforming a 3D design into a 3D object, and follows with a discussion on the current SSE 3D printing developments and their applications in the fields of pharmaceutics, bioprinting and bioelectronics. Finally, the advantages and limitations of this technology are explored, before focusing on its potential clinical applications and suitability for preparing personalised medicines.
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http://dx.doi.org/10.1016/j.jconrel.2021.02.027DOI Listing
April 2021

3D printed tacrolimus suppositories for the treatment of ulcerative colitis.

Asian J Pharm Sci 2021 Jan 9;16(1):110-119. Epub 2020 Jul 9.

FabRx Ltd., Ashford, Kent TN24 0RW, UK.

Ulcerative colitis is a global health problem, affecting millions of individuals worldwide. As an inflammatory condition localised in the large intestine, rectal delivery of immunosuppressive therapies such as tacrolimus is a promising strategy to maximise drug concentration at the site of action whilst minimising systemic side effects. Here, for the first time, self-supporting 3D-printed tacrolimus suppositories were prepared without the aid of moulds using a pharmaceutical semi-solid extrusion (SSE) 3D printer. The suppositories were printed vertically in three different sizes using combinations of two lipid pharmaceutical excipients (Gelucire 44/14 or Gelucire 48/16) and coconut oil. Although both suppository formulations had the appropriate viscosity characteristics for printing, the Gel 44 formulation required less energy and force for extrusion compared to the Gel 48 system. The Gel 44 disintegrated more rapidly but released tacrolimus more slowly than the Gel 48 suppositories. Although the tacrolimus release profiles were significantly different, both suppository systems released more than 80% drug within 120 min. DSC and XRD analysis was inconclusive in determining the solid-state properties of the drug in the suppositories. In summary, this article reports on the fabrication of 3D printed self-supporting suppositories to deliver personalised doses of a narrow therapeutic index drug, with potential benefits for patients with ulcerative colitis.
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http://dx.doi.org/10.1016/j.ajps.2020.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878453PMC
January 2021