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Nanomedicines as emerging platform for simultaneous delivery of cancer therapeutics: new developments in overcoming drug resistance and optimizing anticancer efficacy

Hussain Z, Arooj M, Malik A, Hussain F, Safdar H, Khan S, et al.

Artif Cells Nanomed Biotechnol, 2018;46(sup2):1015-1024.
PMID: 29873531 DOI: 10.1080/21691401.2018.1478420

Development and formulation of an efficient and safe therapeutic regimen for cancer theranostics are dynamically challenging. The use of mono-therapeutic cancer regimen is generally restricted to optimal clinical applications, on account of drug resistance and cancer heterogeneity. Combinatorial treatments can employ multi-therapeutics for synergistic anticancer efficacy whilst reducing the potency of individual moieties and diminishing the incidence of associated adverse effects. The combo-delivery of nanotherapeutics can optimize anti-tumor efficacy while reversing the incidence of drug resistance, aiming to homogenize pharmacological profile of drugs, enhance circulatory time, permit targeted drug accumulation, achieve multi-target dynamic approach, optimize target-specific drug binding and ensure sustained drug release at the target site. Numerous nanomedicines/nanotherapeutics have been developed by having dynamic physicochemical, pharmaceutical and pharmacological implications. These innovative delivery approaches have displayed specialized treatment effects, alone or in combination with conventional anticancer approaches (photodynamic therapy, radiotherapy and gene therapy), while reversing drug resistance and potential off-target effects. The current review presents a comprehensive overview of nanocarrier aided multi-drug therapies alongside recent advancements, future prospects, and the pivotal requirements for interdisciplinary research.
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.
Recent Advancement of the Current Aspects of g-C3 N4 for its Photocatalytic Applications in Sustainable Energy System

Hayat A, Sohail M, Ali Shah Syed J, Al-Sehemi AG, Mohammed MH, Al-Ghamdi AA, et al.

Chem Rec, 2022 Feb 09.
PMID: 35138017 DOI: 10.1002/tcr.202100310

Being one of the foremost enticing and intriguing innovations, heterogeneous photocatalysis has also been used to effectively gather, transform, and conserve sustainable sun's radiation for the production of efficient and clean fossil energy as well as a wide range of ecological implications. The generation of solar fuel-based water splitting and CO2 photoreduction is excellent for generating alternative resources and reducing global warming. Developing an inexpensive photocatalyst can effectively split water into hydrogen (H2 ), oxygen (O2 ) sources, and carbon dioxide (CO2 ) into fuel sources, which is a crucial problem in photocatalysis. The metal-free g-C3 N4 photocatalyst has a high solar fuel generation potential. This review covers the most recent advancements in g-C3 N4 preparation, including innovative design concepts and new synthesis methods, and novel ideas for expanding the light absorption of pure g-C3 N4 for photocatalytic application. Similarly, the main issue concerning research and prospects in photocatalysts based g-C3 N4 was also discussed. The current dissertation provides an overview of comprehensive understanding of the exploitation of the extraordinary systemic and characteristics, as well as the fabrication processes and uses of g-C3 N4 .
Recent Advances and Future Perspectives of Metal-Based Electrocatalysts for Overall Electrochemical Water Splitting

Hayat A, Sohail M, Ali H, Taha TA, Qazi HIA, Ur Rahman N, et al.

Chem Rec, 2022 Nov 21.
PMID: 36408911 DOI: 10.1002/tcr.202200149

Recently, the growing demand for a renewable and sustainable fuel alternative is contingent on fuel cell technologies. Even though it is regarded as an environmentally sustainable method of generating fuel for immediate concerns, it must be enhanced to make it extraordinarily affordable, and environmentally sustainable. Hydrogen (H2 ) synthesis by electrochemical water splitting (ECWS) is considered one of the foremost potential prospective methods for renewable energy output and H2 society implementation. Existing massive H2 output is mostly reliant on the steaming reformation of carbon fuels that yield CO2 together with H2 and is a finite resource. ECWS is a viable, efficient, and contamination-free method for H2 evolution. Consequently, developing reliable and cost-effective technology for ECWS was a top priority for scientists around the globe. Utilizing renewable technologies to decrease total fuel utilization is crucial for H2 evolution. Capturing and transforming the fuel from the ambient through various renewable solutions for water splitting (WS) could effectively reduce the need for additional electricity. ECWS is among the foremost potential prospective methods for renewable energy output and the achievement of a H2 -based economy. For the overall water splitting (OWS), several transition-metal-based polyfunctional metal catalysts for both cathode and anode have been synthesized. Furthermore, the essential to the widespread adoption of such technology is the development of reduced-price, super functional electrocatalysts to substitute those, depending on metals. Many metal-premised electrocatalysts for both the anode and cathode have been designed for the WS process. The attributes of H2 and oxygen (O2 ) dynamics interactions on the electrodes of water electrolysis cells and the fundamental techniques for evaluating the achievement of electrocatalysts are outlined in this paper. Special emphasis is paid to their fabrication, electrocatalytic performance, durability, and measures for enhancing their efficiency. In addition, prospective ideas on metal-based WS electrocatalysts based on existing problems are presented. It is anticipated that this review will offer a straight direction toward the engineering and construction of novel polyfunctional electrocatalysts encompassing superior efficiency in a suitable WS technique.
Recent Advancement in Rational Design Modulation of MXene: A Voyage from Environmental Remediation to Energy Conversion and Storage

Hayat A, Sohail M, Qadeer A, Taha TA, Hussain M, Ullah S, et al.

Chem Rec, 2022 Dec;22(12):e202200097.
PMID: 36103617 DOI: 10.1002/tcr.202200097

Use of MXenes (Ti3 C2 Tx ), which belongs to the family of two-dimensional transition metal nitrides and carbides by encompassing unique combination of metallic conductivity and hydrophilicity, is receiving tremendous attention, since its discovery as energy material in 2011. Owing to its precursor selective chemical etching, and unique intrinsic characteristics, the MXene surface properties are further classified into highly chemically active compound, which further produced different surface functional groups i. e., oxygen, fluorine or hydroxyl groups. However, the role of surface functional groups doesn't not only have a significant impact onto its electrochemical and hydrophilic characteristics (i. e., ion adsorption/diffusion), but also imparting a noteworthy effect onto its conductivity, work function, electronic structure and properties. Henceforth, such kind of inherent chemical nature, robust electrochemistry and high hydrophilicity ultimately increasing the MXene application as a most propitious material for overall environment-remediation, electrocatalytic sensors, energy conversion and storage application. Moreover, it is well documented that the role of MXenes in all kinds of research fields is still on a progress stage for their further improvement, which is not sufficiently summarized in literature till now. The present review article is intended to critically discuss the different chemical aptitudes and the diversity of MXenes and its derivates (i. e., hybrid composites) in all aforesaid application with special emphasis onto the improvement of its surface characteristics for the multidimensional application. However, this review article is anticipated to endorse MXenes and its derivates hybrid configuration, which is discussed in detail for emerging environmental decontamination, electrochemical use, and pollutant detection via electrocatalytic sensors, photocatalysis, along with membrane distillation and the adsorption application. Finally, it is expected, that this review article will open up new window for the effective use of MXene in a broad range of environmental remediation, energy conversion and storage application as a novel, robust, multidimensional and more proficient materials.
A Targeted Review of Current Progress, Challenges and Future Perspective of g-C3 N4 based Hybrid Photocatalyst Toward Multidimensional Applications

Hayat A, Sohail M, Anwar U, Taha TA, Qazi HIA, Amina, et al.

Chem Rec, 2023 Jan;23(1):e202200143.
PMID: 36285706 DOI: 10.1002/tcr.202200143

The increasing demand for searching highly efficient and robust technologies in the context of sustainable energy production totally rely onto the cost-effective energy efficient production technologies. Solar power technology in this regard will perceived to be extensively employed in a variety of ways in the future ahead, in terms of the combustion of petroleum-based pollutants, CO2 reduction, heterogeneous photocatalysis, as well as the formation of unlimited and sustainable hydrogen gas production. Semiconductor-based photocatalysis is regarded as potentially sustainable solution in this context. g-C3 N4 is classified as non-metallic semiconductor to overcome this energy demand and enviromental challenges, because of its superior electronic configuration, which has a median band energy of around 2.7 eV, strong photocatalytic stability, and higher light performance. The photocatalytic performance of g-C3 N4 is perceived to be inadequate, owing to its small surface area along with high rate of charge recombination. However, various synthetic strategies were applied in order to incorporate g-C3 N4 with different guest materials to increase photocatalytic performance. After these fabrication approaches, the photocatalytic activity was enhanced owing to generation of photoinduced electrons and holes, by improving light absorption ability, and boosting surface area, which provides more space for photocatalytic reaction. In this review, various metals, non-metals, metals oxide, sulfides, and ferrites have been integrated with g-C3 N4 to form mono, bimetallic, heterojunction, Z-scheme, and S-scheme-based materials for boosting performance. Also, different varieties of g-C3 N4 were utilized for different aspects of photocatalytic application i. e., water reduction, water oxidation, CO2 reduction, and photodegradation of dye pollutants, etc. As a consequence, we have assembled a summary of the latest g-C3 N4 based materials, their uses in solar energy adaption, and proper management of the environment. This research will further well explain the detail of the mechanism of all these photocatalytic processes for the next steps, as well as the age number of new insights in order to overcome the current challenges.
Synthesis of Electrical Conductive Metal-Organic Frameworks for Electrochemical Applications

Shoaib Ahmad Shah S, Altaf Nazir M, Mahmood A, Sohail M, Ur Rehman A, Khurram Tufail M, et al.

Chem Rec, 2024 Jan;24(1):e202300141.
PMID: 37724006 DOI: 10.1002/tcr.202300141

Electrical conductivity is very important property of nanomaterials for using wide range of applications especially energy applications. Metal-organic frameworks (MOFs) are notorious for their low electrical conductivity and less considered for usage in pristine forms. However, the advantages of high surface area, porosity and confined catalytic active sites motivated researchers to improve the conductivity of MOFs. Therefore, 2D electrical conductive MOFs (ECMOF) have been widely synthesized by developing the effective synthetic strategies. In this article, we have summarized the recent trends in developing the 2D ECMOFs, following the summary of potential applications in the various fields with future perspectives.
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.
Fabrication of CoTiO3-TiO2 composite films from a heterobimetallic single source precursor for electrochemical sensing of dopamine

Ehsan MA, Naeem R, Khaledi H, Sohail M, Hakeem Saeed A, Mazhar M

Dalton Trans, 2016 Jun 21;45(25):10222-32.
PMID: 27230711 DOI: 10.1039/c6dt01016d

Cobalt titanate-titania composite oxide films have been grown on FTO-coated glass substrates using a single-source heterometallic complex [Co2Ti4(μ-O)6(TFA)8(THF)6]·THF () which was obtained in quantitative yield from the reaction of diacetatocobalt(ii) tetrahydrate, tetraisopropoxytitanium(iv), and trifluoroacetic acid from a tetrahydrofuran solution. Physicochemical investigations of complex have been carried out by melting point, FT-IR, thermogravimetric and single-crystal X-ray diffraction analyses. CoTiO3-TiO2 films composed of spherical objects of various sizes have been grown from by aerosol-assisted chemical vapor deposition at different temperatures of 500, 550 and 600 °C. Thin films characterized by XRD, Raman and X-ray photoelectron spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis have been explored for electrochemical detection of dopamine (DA). The cyclic voltammetry with the CoTiO3-TiO2 electrode showed a DA oxidation peak at +0.215 V while linear sweep voltammetry displayed a detection limit (LoD) of 0.083 μM and a linear concentration range of 20-300 μM for DA. Thus, the CoTiO3-TiO2 electrode is a potential candidate for the sensitive and selective detection of DA.
Fabrication of pristine Mn2O3 and Ag-Mn2O3 composite thin films by AACVD for photoelectrochemical water splitting

Naeem R, Ali Ehsan M, Yahya R, Sohail M, Khaledi H, Mazhar M

Dalton Trans, 2016 Oct 14;45(38):14928-39.
PMID: 27549401 DOI: 10.1039/c6dt02656g

Pristine Mn2O3 and Ag-Mn2O3 composite thin films have been developed on fluorine doped tin oxide (FTO) coated glass substrates at 450 °C by aerosol assisted chemical vapor deposition (AACVD) using a methanol solution of a 1 : 2 mixture of acetatoargentate(i), Ag(CH3COO), and a newly synthesized manganese complex, [Mn(dmae)2(TFA)4] (1) (dmae = N,N-dimethylaminoethanolate, TFA = trifluoroacetate). The phase purity and stoichiometric composition of the films were investigated by X-ray diffraction (XRD) and Raman spectroscopy techniques. Energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) analyses revealed a Ag to Mn ratio of 1 : 2 and further confirmed the uniform dispersion of Ag nanoparticles into the Mn2O3 structure. Optical studies showed a direct band gap of 2.0 eV for the pristine Mn2O3 film that was lowered to 1.8 eV for Ag-Mn2O3 due to the plasmonic interaction of Ag with Mn2O3. The Ag-Mn2O3 composite film displayed enhanced photocatalytic activity in photoelectrochemical (PEC) water splitting and yielded a photocurrent of 3 mA cm(-2) at 0.7 V versus Ag/AgCl which was 1.6 times higher than a pristine Mn2O3 film alone, under AM 1.5 G illumination (100 mW cm(-2)). The high PEC efficiency is mainly due to the plasmonic effect of Ag nanoparticles, which enhances the visible light absorption, efficient electron-hole separation and high carrier mobility of the Ag-Mn2O3 photoelectrode. The charge carrier density of Ag-Mn2O3 is two times higher than the pristine Mn2O3 as calculated by the Mott-Schottky plot. Based on the PEC studies a mechanism is proposed to elucidate the high activity of Ag-Mn2O3 in PEC water splitting.
Natural and synthetic polymer-based smart biomaterials for management of ulcerative colitis: a review of recent developments and future prospects

Sohail M, Mudassir, Minhas MU, Khan S, Hussain Z, de Matas M, et al.

Drug Deliv Transl Res, 2019 04;9(2):595-614.
PMID: 29611113 DOI: 10.1007/s13346-018-0512-x

Ulcerative colitis (UC) is an inflammatory disease of the colon that severely affects the quality of life of patients and usually responds well to anti-inflammatory agents for symptomatic relief; however, many patients need colectomy, a surgical procedure to remove whole or part of the colon. Though various types of pharmacological agents have been employed for the management of UC, the lack of effectiveness is usually predisposed to various reasons including lack of target-specific delivery of drugs and insufficient drug accumulation at the target site. To overcome these glitches, many researchers have designed and characterized various types of versatile polymeric biomaterials to achieve target-specific delivery of drugs via oral route to optimize their targeting efficiency to the colon, to improve drug accumulation at the target site, as well as to ameliorate off-target effects of chemotherapy. Therefore, the aim of this review was to summarize and critically discuss the pharmaceutical significance and therapeutic feasibility of a wide range of natural and synthetic biomaterials for efficient drug targeting to colon and rationalized treatment of UC. Among various types of biomaterials, natural and synthetic polymer-based hydrogels have shown promising targeting potential due to their innate pH responsiveness, sustained and controlled release characteristics, and microbial degradation in the colon to release the encapsulated drug moieties. These characteristic features make natural and synthetic polymer-based hydrogels superior to conventional pharmacological strategies for the management of UC.
PEGylation: a promising strategy to overcome challenges to cancer-targeted nanomedicines: a review of challenges to clinical transition and promising resolution

Hussain Z, Khan S, Imran M, Sohail M, Shah SWA, de Matas M

Drug Deliv Transl Res, 2019 06;9(3):721-734.
PMID: 30895453 DOI: 10.1007/s13346-019-00631-4

On account of heterogeneity, intrinsic ability of drug resistance, and the potential to invade to other parts of the body (malignancy), the development of a rational anticancer regimen is dynamically challenging. Chemotherapy is considered the gold standard for eradication of malignancy and mitigation of its reoccurrence; nevertheless, it has also been associated with detrimental effects to normal tissues owing to its nonselectivity and nominal penetration into the tumor tissues. In recent decades, nanotechnology-guided interventions have been well-acclaimed due to their ability to facilitate target-specific delivery of drugs, avoidance of nontarget distribution, alleviated systemic toxicity, and maximized drug internalization into cancer cells. Despite their numerous biomedical advantages, clinical translation of nanotechnology-mediated regimens is challenging due to their short plasma half-life and early clearance. PEGylation of nanomedicines has been adapted as an efficient strategy to extend plasma half-life and diminished early plasma clearance via alleviating the opsonization (uptake by monocytes and macrophages) of drug nanocarriers. PEGylation provides "stealth" properties to nanocarrier's surfaces which diminished their recognition or uptake by cellular immune system, leading to longer circulation time, reduced dosage and frequency, and superior site-selective delivery of drugs. Therefore, this review aims to present a comprehensive overview of the pharmaceutical advantages and therapeutic feasibility of PEGylation of nanocarriers in improving tumor-specific targetability, reversing drug resistance, and improving pharmacokinetic profile of drugs and anticancer efficacy. Challenges to PEGylated cancer nanomedicines, possible adaptations to resolve those challenges, and pivotal requirement for interdisciplinary research for development of rational anticancer regimen have also been pondered.
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
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, 2019 Feb;9(1):284-297.
PMID: 30387048 DOI: 10.1007/s13346-018-00596-w

The aim of this study was to employ experimental and molecular modelling approaches to use molecular level interactions to rationalise the selection of suitable polymers for use in the production of stable domperidone (DOMP) nanocrystals with enhanced bioavailability. A low-energy antisolvent precipitation method was used for the preparation and screening of polymers for stable nanocrystals of DOMP. Ethyl cellulose was found to be very efficient in producing stable DOMP nanocrystals with particle size of 130 ± 3 nm. Moreover, the combination of hydroxypropyl methylcellulose and polyvinyl alcohol was also shown to be better in producing DOMP nanocrystals with smaller particle size (200 ± 3.5 nm). DOMP nanosuspension stored at 2-8 °C and at room temperature (25 °C) exhibited better stability compared to the samples stored at 40 °C. Crystallinity of the unprocessed and processed DOMP was monitored by differential scanning calorimetry and powder X-ray diffraction. DOMP nanocrystals gave enhanced dissolution rate compared to the unprocessed drug substance. DOMP nanocrystals at a dose of 10 mg/kg in rats showed enhanced bioavailability compared to the raw drug substance and marketed formulation. A significant increase in plasma concentration of 2.6 μg/mL with a significant decrease in time (1 h) to reach maximum plasma concentration was observed for DOMP nanocrystals compared to the raw DOMP. Molecular modelling studies provided underpinning knowledge at the molecular level of the DOMP-polymer nanocrystal interactions and substantiated the experimental studies. This included an understanding of the impact of polymers on the size of nanocrystals and their associated stability characteristics.
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
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, 2019 Apr;9(2):555-577.
PMID: 29450805 DOI: 10.1007/s13346-018-0486-8

Cellulose acetate phthalate-based pH-responsive hydrogel was synthesized for fabrication of polymeric matrix tablets for gastro-protective delivery of loxoprofen sodium. Cellulose acetate phthalate (CAP) was cross-linked with methacrylic acid (MAA) using free radical polymerization technique. Fourier transform infrared (FTIR) spectra confirmed the formation of cross-linked structure of CAP-co-poly(methacrylic acid). Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the thermal stability of polymeric networks, and scanning electron microscopy (SEM) and energy-dispersive X-ray spectrum (EDS) images unveiled that the prepared formulations were porous in nature and thus the developed formulations had shown better diffusibility. Swelling and in vitro drug release was performed at various pHs and maximum swelling and release was obtained at pH 7.4, while swelling and release rate was very low at pH 1.2 which confirmed the pH-responsive behavior of CAP-co-poly(MAA). CAP-co-poly(MAA) copolymer prevents the release of loxoprofen sodium into the stomach due to reduced swelling at gastric pH while showing significant swelling and drug release in the colon. Cytotoxicity studies revealed higher biocompatibility of fabricated hydrogel. Acute oral toxicity studies were performed for the evaluation and preliminary screening of safety profile of the developed hydrogels. Matrix tablets were evaluated for release behavior at simulated body pH. The investigations performed for analysis of hydrogels and fabricated matrix tablets indicated the controlled drug release and gastro-protective drug delivery of CAP-co-poly(MAA) hydrogels and pH-sensitive matrix tablets for targeted delivery of gastro-sensitive/irritative agents. Graphical abstract.
Fulltext A new strategy for taste masking of azithromycin antibiotic: development, characterization, and evaluation of azithromycin titanium nanohybrid for masking of bitter taste using physisorption and panel testing studies

Amin F, Khan S, Shah SMH, Rahim H, Hussain Z, Sohail M, et al.

Drug Des Devel Ther, 2018;12:3855-3866.
PMID: 30510401 DOI: 10.2147/DDDT.S183534

Background: The obnoxious bitter taste of orally taken antibiotics is one of the biggest problems in the treatment of children. The pediatric population cannot tolerate the bitter taste of drugs and vomit out which ultimately leads to suboptimal therapeutic value, grimace and mental stress so it is the challenging task for the formulation scientists to formulate a palatable formulation particularly to overcome address the issue.
Purpose of study: The study aimed to mask and evaluate the unpleasant bitter taste of azithro-mycin (AZ) in the dry suspension dosage form by physisorption technique.
Materials and methods: AZ was selected as an adsorbent and titanium dioxide nanoparticles as adsorbate. The AZ nanohybrids (AZN) were prepared by treating fixed amount of adsorbent with a varied amount of adsorbate, prepared separately by dispersing it in an aqueous medium. The mixture was sonicated, stirred followed by filtration and drying. The AZN produced were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-rays (EDX), powder X-ray diffraction (PXRD), HPLC and Fourier-transformed infrared (FTIR). The optimized nanohybrid was blended with other excipients to get stable and taste masked dry suspension dosage form.
Results: The results confirmed the adsorption of titanium dioxide nanoparticles on the surface of AZ. The fabricated optimized formulation was subjected for taste masking by panel testing and accelerated stability studies. The results showed a remarkable improvement in bitter taste masking, inhibiting throat bite without affecting the dissolution rate. The product showed an excellent stability both in dry and reconstituted suspension. The optimized formulation of AZN and was found stable when subjected to physical and chemical stability studies, this is because of short and single step process which interns limits the exposure of the product to various environmental factors that could potentially affect the stability of the product. The dissolution rate of the optimized formulation of AZN was compared with its marketed counterpart, showing the same dissolution rate compared to its marketed formulation.
Conclusion: The current study concludes that, by fabricating AZ-titanium nanohybrids using physisorption can effectively mask the bitter taste of the drug. The palatability and stability of azithromycin formulation was potentially enhanced without affecting its dissolution rate.
Fulltext Engineering of Naproxen Loaded Polymer Hybrid Enteric Microspheres for Modified Release Tablets: Development, Characterization, in silico Modelling and in vivo Evaluation

Hameed HA, Khan S, Shahid M, Ullah R, Bari A, Ali SS, et al.

Drug Des Devel Ther, 2020;14:27-41.
PMID: 32021089 DOI: 10.2147/DDDT.S232111

BACKGROUND: Naproxen (NP) is a non-steroidal anti-inflammatory drug with poor aqueous solubility and low oral bioavailability, which may lead to therapeutic failure. NP causes crucial GIT irritation, bleeding, and peptic and duodenal ulcers.
PURPOSE OF THE STUDY: This study aimed to engineer and characterize polymer hybrid enteric microspheres using an integrated (experimental and molecular modelling) approach with further development to solid dosage form with modified drug release kinetics and improved bioavailability.
MATERIALS AND METHODS: NP loaded polymer hybrid enteric microspheres (PHE-Ms) were fabricated by using a modified solvent evaporation technique coupled with molecular modelling (MM) approach. The PHE-Ms were characterized by particle size, distribution, morphology, crystallinity, EE, drug-polymer compatibility, and DSC. The optimized NP loaded PHE-Ms were further subjected to downstream procedures including tablet dosage form development, stability studies and comparative in vitro-in vivo evaluation.
RESULTS: The hydrophobic polymer EUD-L100 and hydrophilic polymer HPMC-E5 delayed and modified drug release at intestinal pH while imparting retardation of NP release at gastric pH to diminish the gastric side effects. The crystallinity of the NP loaded PHE-Ms was established through DSC and P (XRD). The particle size for the developed formulations of PEH-Ms (M1-M5) was in the range from 29.06 ±7.3-74.31 ± 17.7 μm with Span index values of 0.491-0.69, respectively. The produced NP hybrid microspheres demonstrated retarded drug release at pH 1.2 and improved dissolution at pH 6.8. The in vitro drug release patterns were fitted to various release kinetic models and the best-followed model was the Higuchi model with a release exponent "n" value > 0.5. Stability studies at different storage conditions confirmed stability of the NP loaded PHE-Ms based tablets (P<0.05). The molecular modelling (MM) study resulted in adequate binding energy of co-polymer complex SLS-Eudragit-HPMC-Naproxen (-3.9 kcal/mol). In contrast to the NP (unprocessed) and marketed formulations, a significant increase in the Cmax of PHE-MT1 (44.41±4.43) was observed.
CONCLUSION: The current study concludes that developing NP loaded PHE-Ms based tablets could effectively reduce GIT consequences with restored therapeutic effects. The modified release pattern could improve the dissolution rate and enhancement of oral bioavailability. The MM study strengthens the polymer-drug relationship in microspheres.
Fulltext Potential application of nanotechnology in the treatment, diagnosis, and prevention of schistosomiasis

Qadeer A, Ullah H, Sohail M, Safi SZ, Rahim A, Saleh TA, et al.

Front Bioeng Biotechnol, 2022;10:1013354.
PMID: 36568300 DOI: 10.3389/fbioe.2022.1013354

Schistosomiasis is one of the neglected tropical diseases that affect millions of people worldwide. Globally, it affects economically poor countries, typically due to a lack of proper sanitation systems, and poor hygiene conditions. Currently, no vaccine is available against schistosomiasis, and the preferred treatment is chemotherapy with the use of praziquantel. It is a common anti-schistosomal drug used against all known species of Schistosoma. To date, current treatment primarily the drug praziquantel has not been effective in treating Schistosoma species in their early stages. The drug of choice offers low bioavailability, water solubility, and fast metabolism. Globally drug resistance has been documented due to overuse of praziquantel, Parasite mutations, poor treatment compliance, co-infection with other strains of parasites, and overall parasitic load. The existing diagnostic methods have very little acceptability and are not readily applied for quick diagnosis. This review aims to summarize the use of nanotechnology in the treatment, diagnosis, and prevention. It also explored safe and effective substitute approaches against parasitosis. At this stage, various nanomaterials are being used in drug delivery systems, diagnostic kits, and vaccine production. Nanotechnology is one of the modern and innovative methods to treat and diagnose several human diseases, particularly those caused by parasite infections. Herein we highlight the current advancement and application of nanotechnological approaches regarding the treatment, diagnosis, and prevention of schistosomiasis.
Fulltext Psychosocial safety climate and self-efficacy: Moderating role of job-related expectations in Pakistani private-sector employees during the COVID-19 pandemic

Maqsood S, Sohail M, Naeem F, Nazri M, Fatima D

Front Psychol, 2022;13:1016050.
PMID: 36926534 DOI: 10.3389/fpsyg.2022.1016050

The labor force in Pakistan comprises 59.8 million individuals. The employees have faced major changes in work dynamics and psychosocial safety climate during the COVID-19 pandemic. The purpose of the current study is to find the relationship between psychosocial safety climate, self-efficacy, and job-related expectations. It explores the moderating role of job-related expectations on the relationship between psychosocial safety climate and self-efficacy. It was hypothesized that there is likely to be a significant relationship between psychosocial safety climate, self-efficacy, and job-related expectations, job-related expectations are likely to moderate the relationship between psychosocial safety climate and self-efficacy, and there are likely to be differences between married and unmarried employees; men and women; satisfied and unsatisfied employees with respect to psychosocial safety, self-efficacy, and job-related expectations. A correlational research design and a convenience sampling strategy were used. A total of 281 employees (M = 30.74 years, SD = 10.99) of the private-sector (including educational, industrial, and IT) organizations during the COVID-19 pandemic were part of the study. Results show that psychosocial safety climate had a positive significant relationship with job-related expectations and self-efficacy. Job expectations also significantly correlated with self-efficacy. There were significant differences in measures of study variables with respect to gender, marital status, and employee satisfaction. This research has implications for administration, managers, policymakers, and organizational psychologists.

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