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Retraction Note: pH-responsive CAP-co-poly(methacrylic acid)-based hydrogel as an efficient platform for controlled gastrointestinal delivery: fabrication, characterization, in vitro and in vivo toxicity evaluation

Shah SA, Sohail M, Minhas MU, Nisar-Ur-Rehman, Khan S, Hussain Z, et al.

Drug Deliv Transl Res, 2024 Apr 11.
PMID: 38602616 DOI: 10.1007/s13346-024-01600-2
Integration of statistical and simulation analyses for ternary hybrid nanofluid over a moving surface with melting heat transfer

Rehman AU, Abbas Z, Hussain Z, Hasnain J, Asma M

Nanotechnology, 2024 Apr 09;35(26).
PMID: 38522098 DOI: 10.1088/1361-6528/ad373d

In industrial and engineering fields including lamination, melt-spinning, continuous casting, and fiber spinning, the flow caused by a continually moving surface is significant. Therefore, the problem of ternary hybrid nanofluid flow over a moving surface is studied. This study explores the stability and statistical analyses of the magnetohydrodynamics (MHD) forced flow of the ternary hybrid nanofluid with melting heat transfer phenomena. The impacts of viscous dissipation, Joule heating, and thermal radiation are also included in the flow. Different fluids including ternary hybrid nanofluid, hybrid nanofluids, and nanofluids with base fluid ethylene glycol (EG) are examined and compared, where magnetite (Fe3O4) and silica (SiO2) are taken as the magnetic nanomaterials while silver (Ag) is chosen as the nonmagnetic nanomaterial. The skin friction coefficient and the local Nusselt number are estimated through regression analysis. By employing similarity transformations, the governing partial differential equations are converted into non-linear ordinary differential equations. Then, the least square method is applied to solve the equations analytically. Dual solutions are established in a particular range of moving parameterλ. Due to this, a stability test is implemented to find the stable solution by using the bvp4c function in MATLAB software. It is found that the first solution is the stable one while the second is unstable. The use of ternary hybrid nanomaterials improves the heat transport rate. The increasing values of the Eckert number enlarge the heat passage. The fluid velocity and temperature profiles for nonmagnetic nanomaterials are higher than that of magnetic nanomaterials. The uniqueness and originality of this study stems from the fact that, to the best of the authors' knowledge, it is the first to use this combination technique.
Improving the substrate binding of acetyl-CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering

Ali I, Wei DQ, Khan A, Feng Y, Waseem M, Hussain Z, et al.

Biotechnol Appl Biochem, 2024 Apr;71(2):402-413.
PMID: 38287712 DOI: 10.1002/bab.2548

Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.
Correction to: Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction

Ndlovu ST, Ullah N, Khan S, Ramharack P, Soliman M, de Matas M, et al.

Drug Deliv Transl Res, 2024 Feb 28.
PMID: 38416387 DOI: 10.1007/s13346-024-01554-5
Photoreduction of Cr(VI) in wastewater by anodic nanoporous Nb2O5 formed at high anodizing voltage and electrolyte temperature

Alias N, Hussain Z, Tan WK, Kawamura G, Muto H, Matsuda A, et al.

Environ Sci Pollut Res Int, 2022 Aug;29(40):60600-60615.
PMID: 35426025 DOI: 10.1007/s11356-022-20005-7

In this study, nanoporous anodic film was produced by anodization of niobium, Nb in a fluoride ethylene glycol electrolyte. The effect of anodization voltage and electrolyte temperature was studied to find an optimum condition for circular, ordered, and uniform pore formation. The diameter of the pores was found to be larger when the applied voltage was increased from 20 to 80 V. The as-anodized porous film was also observed to comprise of nanocrystallites which formed due to high field-induced crystallization. The nanocrystallites grew into orthorhombic Nb2O5 after post-annealing treatment. The Cr(VI) photoreduction property of both the as-anodized and annealed Nb2O5 samples obtained using an optimized condition (anodization voltage: 60 V, electrolyte temperature: 70 °C) was compared. Interestingly, the as-anodized Nb2O5 film was found to display better photoreduction of Cr(VI) than annealed Nb2O5. However, in terms of stability, the annealed Nb2O5 presented high photocatalytic efficiency for each cycle whereas the as-anodized Nb2O5 showed degradation in photocatalytic performance when used continually.
Fulltext Vaccine contamination: Causes and control

Chooi WH, Ng PW, Hussain Z, Ming LC, Ibrahim B, Koh D

Vaccine, 2022 Mar 15;40(12):1699-1701.
PMID: 35210120 DOI: 10.1016/j.vaccine.2022.02.034
Fulltext Computational modelling of potentially emerging SARS-CoV-2 spike protein RBDs mutations with higher binding affinity towards ACE2: A structural modelling study

Khan A, Hussain S, Ahmad S, Suleman M, Bukhari I, Khan T, et al.

Comput Biol Med, 2022 02;141:105163.
PMID: 34979405 DOI: 10.1016/j.compbiomed.2021.105163

The spike protein of SARS-CoV-2 and the host ACE2 receptor plays a vital role in the entry to the cell. Among which the hotspot residue 501 is continuously subjected to positive selection pressure and induces unusual virulence. Keeping in view the importance of the hot spot residue 501, we predicted the potentially emerging structural variants of 501 residue. We analyzed the binding pattern of wild type and mutants (Spike RBD) to the ACE2 receptor by deciphering variations in the amino acids' interaction networks by graph kernels along with evolutionary, network metrics, and energetic information. Our analysis revealed that N501I, N501T, and N501V increase the binding affinity and alter the intra and inter-residue bonding networks. The N501T has shown strong positive selection and fitness in other animals. Docking results and repeated simulations (three times) confirmed the structural stability and tighter binding of these three variants, correlated with the previous results following the global stability trend. Consequently, we reported three variants N501I, N501T, and N501V could worsen the situation further if they emerged. The relations between the viral fitness and binding affinity is a complicated game thus the emergence of high affinity mutations in the SARS-CoV-2 RBD brings up the question of whether or not positive selection favours these mutations or not?
Fulltext The Use of Blockchain Technology in the Health Care Sector: Systematic Review

Elangovan D, Long CS, Bakrin FS, Tan CS, Goh KW, Yeoh SF, et al.

JMIR Med Inform, 2022 Jan 20;10(1):e17278.
PMID: 35049516 DOI: 10.2196/17278

BACKGROUND: Blockchain technology is a part of Industry 4.0's new Internet of Things applications: decentralized systems, distributed ledgers, and immutable and cryptographically secure technology. This technology entails a series of transaction lists with identical copies shared and retained by different groups or parties. One field where blockchain technology has tremendous potential is health care, due to the more patient-centric approach to the health care system as well as blockchain's ability to connect disparate systems and increase the accuracy of electronic health records.
OBJECTIVE: The aim of this study was to systematically review studies on the use of blockchain technology in health care and to analyze the characteristics of the studies that have implemented blockchain technology.
METHODS: This study used a systematic review methodology to find literature related to the implementation aspect of blockchain technology in health care. Relevant papers were searched for using PubMed, SpringerLink, IEEE Xplore, Embase, Scopus, and EBSCOhost. A quality assessment of literature was performed on the 22 selected papers by assessing their trustworthiness and relevance.
RESULTS: After full screening, 22 papers were included. A table of evidence was constructed, and the results of the selected papers were interpreted. The results of scoring for measuring the quality of the publications were obtained and interpreted. Out of 22 papers, a total of 3 (14%) high-quality papers, 9 (41%) moderate-quality papers, and 10 (45%) low-quality papers were identified.
CONCLUSIONS: Blockchain technology was found to be useful in real health care environments, including for the management of electronic medical records, biomedical research and education, remote patient monitoring, pharmaceutical supply chains, health insurance claims, health data analytics, and other potential areas. The main reasons for the implementation of blockchain technology in the health care sector were identified as data integrity, access control, data logging, data versioning, and nonrepudiation. The findings could help the scientific community to understand the implementation aspect of blockchain technology. The results from this study help in recognizing the accessibility and use of blockchain technology in the health care sector.
Nanoporous anodic Nb2O5 with pore-in-pore structure formation and its application for the photoreduction of Cr(VI)

Alias N, Hussain Z, Tan WK, Kawamura G, Muto H, Matsuda A, et al.

Chemosphere, 2021 Nov;283:131231.
PMID: 34144283 DOI: 10.1016/j.chemosphere.2021.131231

An anodic film with a nanoporous structure was formed by anodizing niobium at 60 V in fluorinated ethylene glycol (fluoride-EG). After 30 min of anodization, the anodic film exhibited a "pore-in-pore" structure; that is, there were smaller pores growing inside larger pores. The as-anodized film was weakly crystalline and became orthorhombic Nb2O5 after heat treatment. The energy band gap of the annealed nanoporous Nb2O5 film was 2.9 eV. A photocatalytic reduction experiment was performed on Cr(VI) under ultraviolet (UV) radiation by immersing the nanoporous Nb2O5 photocatalyst in a Cr(VI) solution at pH 2. The reduction process was observed to be very slow; hence, ethylenediaminetetraacetic acid (EDTA) was added as an organic hole scavenger, which resulted in 100% reduction after 45 min of irradiation. The photocatalytic reduction experiment was also performed under visible light, and findings showed that complete reduction achieved after 120 min of visible light exposure.
Fulltext Norfloxacin Loaded Lipid Polymer Hybrid Nanoparticles for Oral Administration: Fabrication, Characterization, In Silico Modelling and Toxicity Evaluation

Khan MA, Khan S, Kazi M, Alshehri SM, Shahid M, Khan SU, et al.

Pharmaceutics, 2021 Oct 06;13(10).
PMID: 34683925 DOI: 10.3390/pharmaceutics13101632

Norfloxacin (NOR), widely employed as an anti-bacterial drug, has poor oral bioavailability. Nano based drug delivery systems are widely used to overcome the existing oral bioavailability challenges. Lipid-Polymer Hybrid Nanoparticles (LPHNs) exhibit the distinctive advantages of both polymeric and liposomes nanoparticles, while excluding some of their disadvantages. In the current study, NOR loaded LPHNs were prepared, and were solid amorphous in nature, followed by in vitro and in vivo evaluation. The optimized process conditions resulted in LPHNs with the acceptable particle size 121.27 nm, Polydispersity Index (PDI) of 0.214 and zeta potential of -32 mv. The addition of a helper lipid, oleic acid, and polymers, ethyl cellulose, substantially increased the encapsulation efficiency (EE%) (65% to 97%). In vitro study showed a sustained drug release profile (75% within 12 h) for NOR LPHNs. The optimized NOR LPHNs showed a significant increase (p < 0.05) in bioavailability compared to the commercial product. From the acute toxicity study, the LD50 value was found to be greater than 1600 mg/kg. The molecular modelling studies substantiated the experimental results with the best combination of polymers and surfactants that produced highly stable LPHNs. Therefore, LPHNs proved to be a promising system for the delivery of NOR, as well as for other antibiotics and hydrophobic drugs.
Fulltext Pomegranate peels waste hydrolyzate optimization by Response Surface Methodology for Bioethanol production

Chaudhary A, Hussain Z, Aihetasham A, El-Sharnouby M, Abdul Rehman R, Azmat Ullah Khan M, et al.

Saudi J Biol Sci, 2021 Sep;28(9):4867-4875.
PMID: 34466060 DOI: 10.1016/j.sjbs.2021.06.081

Unwanted agricultural waste is largely comprised of lignocellulosic substrate which could be transformed into sugars. The production of bioethanol from garbage manifested an agreeable proposal towards waste management as well as energy causation. The goal of this work is to optimize parameters for generation of bioethanol through fermentation by different yeast strains while Saccharomyces cerevisiae used as standard strain. The low cost fermentable sugars from pomegranate peels waste (PPW) were obtained by hydrolysis with HNO3 (1 to 5%). The optimum levels of hydrolysis time and temperature were elucidated via RSM (CCD) ranging from 30 to 60 min and 50 to 100 °C respectively. The result shows that optimum values (g/L) for reducing sugars was 61.45 ± 0.01 while for total carbohydrates was 236 ± 0.01. These values were found when PPW was hydrolyzed with 3% HNO3, at 75 °C for one hour. The hydrolyzates obtained from the dilute HNO3 pretreated PPW yielded a maximum of 0.43 ± 0.04, 0.41 ± 0.03 g ethanol per g of reducing sugars by both Metchnikowia sp. Y31 and M. cibodasensis Y34 at day 7 of ethanologenic experiment. The current study exhibited that by fermentation of dilute HNO3 hydrolyzates of PPW could develop copious amount of ethanol by optimized conditions.
Roles of social media and counselling support in reducing anxiety among Malaysian during Covid-19 pandemic

Ahmad NS, Hussain Z, Abd Hamid HS, Khairani AZ

Int J Disaster Risk Reduct, 2021 Sep;63:102456.
PMID: 36567870 DOI: 10.1016/j.ijdrr.2021.102456

Covid-19 pandemic has created crises among some Malaysians. The crises have both opportunity and threat impacts. Without proper intervention, some people will develop stress, anxiety, and depression. This study aims to explore the emotional anxiety that exists in the society due to Covid-19 pandemic and the roles of social media and counselling support in reducing anxiety among Malaysians. This quantitative research involved online survey throughout the country. The online survey is administered during the First Phase and the Second Phase of Movement Control Order (MCO). The survey contains 13 items which cover three domain: i) anxiety, ii) roles of social media, and iii) roles of counselling support in reducing anxiety among members of the society. There were 8375 respondents from various age groups, locations, as well as economic and educational statuses involved in the study. Data were analysed using descriptive and inferential analysis. Majority of 7233 (86.6%) respondents felt anxious due to Covid-19 pandemic. A total of 7871 respondents (94%) followed the latest updates on Covid-19 to reduce their anxiety. They used social media such as Facebook, Instagram and Twitter to gather information and follow the updates through television and press conference. A total of 5251 respondents (62.7%) were aware of the counselling support provided during the MCO, and 4603 respondents (55%) felt comfortable to have counselling support by phone. The findings will contribute to knowledge on the society's emotional anxiety in facing Covid-19. It reflects the actual situation happened in Malaysia during Covid-19 and MCO.
Curcumin-laden hyaluronic acid-co-Pullulan-based biomaterials as a potential platform to synergistically enhance the diabetic wound repair

Shah SA, Sohail M, Minhas MU, Khan S, Hussain Z, Mahmood A, et al.

Int J Biol Macromol, 2021 Aug 31;185:350-368.
PMID: 34171251 DOI: 10.1016/j.ijbiomac.2021.06.119

Injectable hydrogel with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report hyaluronic acid and Pullulan-based injectable hydrogel loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade compared to other treatment groups. The physical interaction and self-assembly of hyaluronic acid-Pullulan-grafted-pluronic F127 injectable hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The CUR-laden hyaluronic acid-Pullulan-g-F127 injectable hydrogel promptly undergoes a sol-gel transition and has proved to potentiate wound healing in a streptozotocin-induced diabetic rat model by promoting 93% of wound closure compared to other groups having 35%, 38%, and 62%. The comparative in vivo study and histological examination was conducted which demonstrated an expeditious recovery rate by significantly reducing the wound healing days i.e. 35 days in a control group, 33 days in the CUR suspension group, 21 days in unloaded injectable, and 13 days was observed in CUR loaded hydrogel group. Furthermore, we suggest that the injectable hydrogel laden with CUR showed a prompt wound healing potential by increasing the cell proliferation and serves as a drug delivery platform for sustained and targeted delivery of hydrophobic moieties.
Fulltext Design of an FPGA-Based Fuzzy Feedback Controller for Closed-Loop FES in Knee Joint Model

Noorsal E, Arof S, Yahaya SZ, Hussain Z, Kho D, Mohd Ali Y

Micromachines (Basel), 2021 Aug 16;12(8).
PMID: 34442590 DOI: 10.3390/mi12080968

Functional electrical stimulation (FES) device has been widely used by spinal cord injury (SCI) patients in their rehab exercises to restore motor function to their paralysed muscles. The major challenge of muscle contraction induced by FES is early muscle fatigue due to the open-loop stimulation strategy. To reduce the early muscle fatigue phenomenon, a closed-loop FES system is proposed to track the angle of the limb's movement and provide an accurate amount of charge according to the desired reference angle. Among the existing feedback controllers, fuzzy logic controller (FLC) has been found to exhibit good control performance in handling complex non-linear systems without developing any complex mathematical model. Recently, there has been considerable interest in the implementation of FLC in hardware embedded systems. Therefore, in this paper, a digital fuzzy feedback controller (FFC) embedded in a field-programmable gate array (FPGA) board was proposed. The digital FFC mainly consists of an analog-to-digital converter (ADC) Data Acquisition and FLC sub-modules. The FFC was designed to monitor and control the progress of knee extension movement by regulating the stimulus pulse width duration to meet the target angle. The knee is expected to extend to a maximum reference angle setting (70°, 40° or 30°) from its normal position of 0° once the stimulus charge is applied to the muscle by the FES device. Initially, the FLC was modelled using MATLAB Simulink. Then, the FLC was hardcoded into digital logic using hardware description language (HDL) Verilog codes. Thereafter, the performance of the digital FLC was tested with a knee extension model using the HDL co-simulation technique in MATLAB Simulink. Finally, for real-time verification, the designed digital FFC was downloaded to the Intel FPGA (DE2-115) board. The digital FFC utilized only 4% of the total FPGA (Cyclone IV E) logic elements (LEs) and required 238 µs to regulate stimulus pulse width data, including 3 µs for the FLC computation. The high processing speed of the digital FFC enables the stimulus pulse width duration to be updated every stimulation cycle. Furthermore, the implemented digital FFC has demonstrated good control performance in accurately controlling the stimulus pulse width duration to reach the desired reference angle with very small overshoot (1.4°) and steady-state error (0.4°). These promising results are very useful for a real-world closed-loop FES application.
Cell membrane cloaked nanomedicines for bio-imaging and immunotherapy of cancer: Improved pharmacokinetics, cell internalization and anticancer efficacy

Hussain Z, Rahim MA, Jan N, Shah H, Rawas-Qalaji M, Khan S, et al.

J Control Release, 2021 07 10;335:130-157.
PMID: 34015400 DOI: 10.1016/j.jconrel.2021.05.018

Despite enormous advancements in the field of oncology, the innocuous and effectual treatment of various types of malignancies remained a colossal challenge. The conventional modalities such as chemotherapy, radiotherapy, and surgery have been remained the most viable options for cancer treatment, but lacking of target-specificity, optimum safety and efficacy, and pharmacokinetic disparities are their impliable shortcomings. Though, in recent decades, numerous encroachments in the field of onco-targeted drug delivery have been adapted but several limitations (i.e., short plasma half-life, early clearance by reticuloendothelial system, immunogenicity, inadequate internalization and localization into the onco-tissues, chemoresistance, and deficient therapeutic efficacy) associated with these onco-targeted delivery systems limits their clinical viability. To abolish the aforementioned inadequacies, a promising approach has been emerged in which stealthing of synthetic nanocarriers has been attained by cloaking them into the natural cell membranes. These biomimetic nanomedicines not only retain characteristics features of the synthetic nanocarriers but also inherit the cell-membrane intrinsic functionalities. In this review, we have summarized preparation methods, mechanism of cloaking, and pharmaceutical and therapeutic superiority of cell-membrane camouflaged nanomedicines in improving the bio-imaging and immunotherapy against various types of malignancies. These pliable adaptations have revolutionized the current drug delivery strategies by optimizing the plasma circulation time, improving the permeation into the cancerous microenvironment, escaping the immune evasion and rapid clearance from the systemic circulation, minimizing the immunogenicity, and enabling the cell-cell communication via cell membrane markers of biomimetic nanomedicines. Moreover, the preeminence of cell-membrane cloaked nanomedicines in improving the bio-imaging and theranostic applications, alone or in combination with phototherapy or radiotherapy, have also been pondered.
Fulltext Educational resource for antimicrobial resistance and stewardship for dentistry programmes: a research protocol

Ang CY, Dhaliwal JS, Muharram SH, Akkawi ME, Hussain Z, Rahman H, et al.

BMJ Open, 2021 07 07;11(7):e048609.
PMID: 34233993 DOI: 10.1136/bmjopen-2021-048609

INTRODUCTION: Antimicrobial resistance (AMR) is a global public and patient safety issue. With the high AMR risk, ensuring that the next generation of dentists that have optimal knowledge and confidence in the area of AMR is crucial. A systematic approach is vital to design an AMR content that is comprehensive and clinically relevant. The primary objective of this research study will be to implement a consensus-based approach to elucidate AMR content and curriculum priorities for professional dentistry programmes. This research aims to establish consensus along with eliciting opinion on appropriate AMR topics to be covered in the Bachelor of Dental Surgery syllabus.
METHODS AND ANALYSIS: A three-phase approach to validate content for curriculum guidelines on AMR will be adopted. First, literature review and content analysis were conducted to find out the available pertinent literature in dentistry programmes. A total of 23 potential literature have been chosen for inclusion within this study following literature review and analysis in phase 1. The materials found will be used to draft curriculum on antimicrobials for dentistry programmes. The next phase involves the validation of the drafted curriculum content by recruiting local and foreign experts via a survey questionnaire. Finally, Delphi technique will be conducted to obtain consensus on the important or controversial modifications to the revised curriculum.
ETHICS AND DISSEMINATION: An ethics application is currently under review with the Institute of Health Science Research Ethics Committee, Universiti Brunei Darussalam. All participants are required to provide a written consent form. Findings will be used to identify significant knowledge gaps on AMR aspect in a way that results in lasting change in clinical practice. Moreover, AMR content priorities related to dentistry clinical practice will be determined in order to develop need-based educational resource on microbes, hygiene and prudent antimicrobial use for dentistry programmes.
Smart pH-responsive co-polymeric hydrogels for controlled delivery of capecitabine: Fabrication, Optimization and in vivo toxicology screening

Rehman U, Sarfraz RM, Mahmood A, Hussain Z, Thu HE, Zafar N, et al.

Curr Drug Deliv, 2021 Feb 11.
PMID: 33583374 DOI: 10.2174/1567201818666210212085912

BACKGROUND: Despite exhibiting promising anticancer potential, the clinical significance of capecitabine (a potent prodrug of 5-fluorouracil used for treatment of colorectal cancer) is limited owing to its acidic and enzymatic hydrolysis, lower absorption following the oral administration, poor bioavailability, short plasma half-life and poor patient compliance.
OBJECTIVES: The present study was aimed to fabricate the capecitabine as smart pH-responsive hydrogel network to efficiently facilitate its oral delivery while shielding its stability in the gastric media.
METHODS: The smart pH sensitive HP-β-CD/agarose-g-poly(MAA) hydrogel network was developed using an aqueous free radical polymerization technique. The developed hydrogels were characterized for drug-loading efficiency, structural and compositional features, thermal stability, swelling behaviour, morphology, physical form, and release kinetics. The pH-responsive behaviour of developed hydrogels was established by conducting the swelling and release behaviour at different pH values (1.2 and 7.4), demonstrating significantly higher swelling and release at pH 7.4 as compared with pH 1.2. The capecitabine-loaded hydrogels were also screened for acute oral toxicity in animals by analysing the body weight, water and food intake, dermal toxicity, ocular toxicity, biochemical analysis, and histological examination.
RESULTS: The characteristic evaluations revealed that capecitabine (anticancer agent) was successfully loaded into the hydrogel network. Capecitabine loading was ranged from 71.22% to 90.12%. An interesting feature of hydrogel was its pH-responsive behaviour which triggers release at basic pH (94.25%). Optimum swelling (95%) was seen at pH 7.4. Based upon regression coefficient R2 (0.96 - 0.99) best fit model was zero order. The extensive toxicity evaluations evidenced good safety profile with no signs of oral, dermal or ocular toxicities, as well as no variations in blood parameters and histology of vital organs.
CONCLUSION: Our findings conclusively evinced that the developed hydrogel exhibited excellent pharmaceutical and therapeutic potential and thus can be employed as pH-responsive system for controlled delivery of anticancer agents.
Fulltext Recent Advancements in Stimuli Responsive Drug Delivery Platforms for Active and Passive Cancer Targeting

Rahim MA, Jan N, Khan S, Shah H, Madni A, Khan A, et al.

Cancers (Basel), 2021 Feb 07;13(4).
PMID: 33562376 DOI: 10.3390/cancers13040670

The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.
Multi-functionalization, a Promising Adaptation to Overcome Challenges to Clinical Translation of Nanomedicines as Nano-diagnostics and Nano-therapeutics for Breast Cancer

Moti LAA, Hussain Z, Thu HE, Khan S, Sohail M, Sarfraz RM

Curr Pharm Des, 2021;27(43):4356-4375.
PMID: 34459374 DOI: 10.2174/1381612827666210830092539

BACKGROUND: Breast cancer (BC) is one of the most aggressive and prevalent types of cancer, which is associated with a high rate of mortality and colossal potential of metastasis to other body organs. Conventionally, there are three commonly employed strategies for the treatment of BC including, surgery, radiations and chemotherapy; however, these modalities are associated with several deleterious effects and a high rate of relapse.
OBJECTIVE: This review was aimed to critically discuss and conceptualize existing evidences related to the pharmaceutical significance and therapeutic feasibility of multi-functionalization of nanomedicines for early diagnosis and efficient treatment of BC.
RESULTS: Though the implication of nanotechnology-based modalities has revolutionised the outcomes of diagnosis and treatment of BC; however, the clinical translation of these nanomedicines is facing grandeur challenges. These challenges include recognition by the reticuloendothelial system (RES), short plasma half-life, non-specific accumulation in the non-cancerous cells, and expulsion of the drug(s) by the efflux pump. To circumvent these challenges, various adaptations such as PEGylation, conjugation of targeting ligand(s), and siteresponsive behaviour (i.e., pH-responsiveness, biochemical, or thermal-responsiveness) have been adapted. Similarly, multi-functionalization of nanomedicines has emerged as an exceptional strategy to improve the pharmacokinetic profile, specific targetability to the tumor microenvironment (active targeting) and efficient internalization, and to alleviate the expulsion of internalized drug contents by silencing-off efflux pump.
CONCLUSION: Critical analysis of the available evidences revealed that multi-functionalization of nanomedicines is a plausible and sustainable adaptation for early diagnosis and treatment of BC with better therapeutic outcomes.
Nano-scaled materials may induce severe neurotoxicity upon chronic exposure to brain tissues: A critical appraisal and recent updates on predisposing factors, underlying mechanism, and future prospects

Hussain Z, Thu HE, Elsayed I, Abourehab MAS, Khan S, Sohail M, et al.

J Control Release, 2020 12 10;328:873-894.
PMID: 33137366 DOI: 10.1016/j.jconrel.2020.10.053

Owing to their tremendous potential, the inference of nano-scaled materials has revolutionized many fields including the medicine and health, particularly for development of various types of targeted drug delivery devices for early prognosis and successful treatment of various diseases, including the brain disorders. Owing to their unique characteristic features, a variety of nanomaterials (particularly, ultra-fine particles (UFPs) have shown tremendous success in achieving the prognostic and therapeutic goals for early prognosis and treatment of various brain maladies such as Alzheimer's disease, Parkinson's disease, brain lymphomas, and other ailments. However, serious attention is needful due to innumerable after-effects of the nanomaterials. Despite their immense contribution in optimizing the prognostic and therapeutic modalities, biological interaction of nanomaterials with various body tissues may produce severe nanotoxicity of different organs including the heart, liver, kidney, lungs, immune system, gastro-intestinal system, skin as well as nervous system. However, in this review, we have primarily focused on nanomaterials-induced neurotoxicity of the brain. Following their translocation into different regions of the brain, nanomaterials may induce neurotoxicity through multiple mechanisms including the oxidative stress, DNA damage, lysosomal dysfunction, inflammatory cascade, apoptosis, genotoxicity, and ultimately necrosis of neuronal cells. Our findings indicated that rigorous toxicological evaluations must be carried out prior to clinical translation of nanomaterials-based formulations to avoid serious neurotoxic complications, which may further lead to develop various neuro-degenerative disorders.

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