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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.
Hyaluronic acid, an efficient biomacromolecule for treatment of inflammatory skin and joint diseases: A review of recent developments and critical appraisal of preclinical and clinical investigations

Chen LH, Xue JF, Zheng ZY, Shuhaidi M, Thu HE, Hussain Z

Int J Biol Macromol, 2018 Sep;116:572-584.
PMID: 29772338 DOI: 10.1016/j.ijbiomac.2018.05.068

Hyaluronic acid (HA) plays multifaceted role in regulating various biological processes and maintaining homeostasis into the body. Numerous researches evidenced the biomedical implications of HA in skin repairmen, cancer prognosis, wound healing, tissue regeneration, anti-inflammatory, immunomodulation. The present review was aimed to summarize and critically appraise the recent developments and efficacy of HA for treatment of inflammatory skin and joint diseases. A thorough analysis of the literature revealed that HA based formulations (i.e., gels, creams, autologous graft, thin sheets, soaked gauze, gauze pad, tincture, injection) have shown remarkable efficacy in treating a wide range of inflammatory skin diseases. The safety, tolerability, and efficacy of HA (as intra-articular injection) have also been well-documented for treatment of various types of joint disease including knee osteoarthritic, joint osteoarthritis, canine osteoarthritis, and meniscal swelling. Intra-articular injection of HA produces remarkable reduction in joint pain, synovial inflammation, and articular swelling. A remarkable improvement in chondrocyte density, territorial matrix appearance, reconstitution of superficial amorphous layer of the cartilage, collagen remodelling, and regeneration of meniscus have also been evident in patients treated with HA. Conclusively, we validate that the application/administration of HA is a promising pharmacotherapeutic regimen for treatment of inflammatory skin and joint diseases.
Polymer-wrapped single-walled carbon nanotubes: a transformation toward better applications in healthcare

Chik MW, Hussain Z, Zulkefeli M, Tripathy M, Kumar S, Majeed ABA, et al.

Drug Deliv Transl Res, 2019 04;9(2):578-594.
PMID: 29594914 DOI: 10.1007/s13346-018-0505-9

Carbon nanotubes (CNTs) possess outstanding properties that could be useful in several technological, drug delivery, and diagnostic applications. However, their unique physical and chemical properties are hindered due to their poor solubility. This article review's the different ways and means of solubility enhancement of single-wall carbon nanotubes (SWNTs). The advantages of SWNTs over the multi-walled carbon nanotubes (MWNTs) and the method of non-covalent modification for solubility enhancement has been the key interest in this review. The review also highlights a few examples of dispersant design. The review includes some interesting utility of SWNTs being wrapped with polymer especially in biological media that could mediate proper drug delivery to target cells. Further, the use of wrapped SWNTs with phospholipids, nucleic acid, and amphiphillic polymers as biosensors is of research interest. The review aims at summarizing the developments relating to wrapped SWNTs to generate further research prospects in healthcare.
Exploring recent developments to improve antioxidant, anti-inflammatory and antimicrobial efficacy of curcumin: A review of new trends and future perspectives

Hussain Z, Thu HE, Amjad MW, Hussain F, Ahmed TA, Khan S

Mater Sci Eng C Mater Biol Appl, 2017 Aug 01;77:1316-1326.
PMID: 28532009 DOI: 10.1016/j.msec.2017.03.226

Curcumin derivatives have been well-documented due to their natural antioxidant, antimicrobial and anti-inflammatory activities. Curcuminoids have also gained widespread recognition due to their wide range of other activities which include anti-infective, anti-mutagenic, anticancer, anti-coagulant, antiarthrititc, and wound healing potential. Despite of having a wide range of activities, the inherent physicochemical characteristics (poor water solubility, low bioavailability, chemical instability, photodegradation, rapid metabolism and short half-life) of curcumin derivatives limit their pharmaceutical significance. Aiming to overcome these pharmaceutical issues and improving therapeutic efficacy of curcuminoids, newer strategies have been attempted in recent years. These advanced techniques include polymeric nanoparticles, nanocomposite hydrogels, nanovesicles, nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, polymeric micelles and polymeric blend films. Incorporation of curcumin in these delivery systems has shown improved solubility, transmembrane permeability, long-term stability, improved bioavailability, longer plasma half-life, target-specific delivery, and upgraded therapeutic efficacy. In this review, a range of in vitro and in vivo studies have been critically discussed to explore the pharmaceutical significance and therapeutic viability of the advanced delivery systems to improve antioxidant, anti-inflammatory and antimicrobial efficacies of curcumin and its derivatives.
Phytotherapeutic potential of natural herbal medicines for the treatment of mild-to-severe atopic dermatitis: A review of human clinical studies

Hussain Z, Thu HE, Shuid AN, Kesharwani P, Khan S, Hussain F

Biomed Pharmacother, 2017 Sep;93:596-608.
PMID: 28686974 DOI: 10.1016/j.biopha.2017.06.087

For many decades, natural herbal medicines, polyherbal formulations and/or decoctions of plant-derived materials have widely been accepted as alternative complementary therapies for the treatment, cure or prevention of a wide range of acute and chronic skin diseases including chronic herpes, prurigo, acute and chronic wounds, psoriasis and atopic dermatitis (AD). This review was aimed to summarize and critically discuss about the therapeutic viability and clinical applicability of natural herbal medicines for the treatment of AD in human. The critical analysis of the literature revealed that oral (in the form of capsules, syrup or granules) and/or topical application (alone or in conjunction with wet-wrap dressing and/or acupuncture) of natural herbal medicines exhibit remarkable potential for the treatment of mild-to-severe AD in adults, children, infants and in the pregnant women. In this review, the clinical efficacy of various herbal formulations such as Chinese herbal therapies, Korean medicines, Iranian medicines, honey, natural herbal oils (coconut oil, olive oil and mineral oil), beeswax, dodder seeds and whey for the treatment of AD has been discussed. The clinical anti-AD efficacy of these complementary therapies has been observed in terms of down-regulation in Scoring Atopic Dermatitis (SCORAD) index, erythematic intensity, Children's Dermatology Life Quality Index (CDLQI), Dermatology Life Quality Index (DLQI), pruritus and itching frequency, transepidermal water loss (TEWL) and expression of AD-mediated chemokines. Conclusively, we recognized that natural herbal medicines demonstrate remarkable clinical efficacy when used alone or in conjunction with other complementary therapies for the treatment of AD in patients of all ages as well as pregnant women.
Eurycoma Longifolia as a potential adoptogen of male sexual health: a systematic review on clinical studies

Thu HE, Mohamed IN, Hussain Z, Jayusman PA, Shuid AN

Chin J Nat Med, 2017 Jan;15(1):71-80.
PMID: 28259255 DOI: 10.1016/S1875-5364(17)30010-9

Eurycoma longifolia (EL) has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels. The aim of the present review is to analyze and summarize the literature on human clinical trials which revealed the clinical significance and therapeutic feasibility of EL in improving male sexual health. This systematic review is focused on the following databases: Medline, Wiley Online Library, BioMed Central, Hindawi, Web of Knowledge, PubMed Central and Google Scholar, using search terms such as "Eurycoma longifolia", "EL", "Tongkat Ali", "male sexual health", "sexual infertility", "erectile dysfunction", "male libido", and "testosterone levels". Notably, only human clinical studies published between 2000 and 2014 were selected and thoroughly reviewed for relevant citations. Out of 150 articles, 11 met the inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed remarkable association between the use of EL and the efficacy in the treatment of male sexual disorders, and remaining 4 studies failed to demonstrate sufficient effects on male sexual health. In summary, there is convincing evidence for the prominence of EL in improving the male sexual health. The review also substantiates the use of current methodology in the development of novel and more rationale natural herbal medicines for the management of male sexual disorders.
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.
Nanoencapsulation of betamethasone valerate using high pressure homogenization-solvent evaporation technique: optimization of formulation and process parameters for efficient dermal targeting

Md S, Kuldeep Singh JKA, Waqas M, Pandey M, Choudhury H, Habib H, et al.

Drug Dev Ind Pharm, 2019 Feb;45(2):323-332.
PMID: 30404554 DOI: 10.1080/03639045.2018.1542704

Betamethsone valerate (BMV), a medium potency topical corticosteroid, is one of the most commonly employed pharmacological agents for the management of atopic dermatitis in both adults and children. Despite having remarkable pharmacological efficacy, these agents have limited clinical implication due to poor penetration across the startum cornum (SC). To mitigate issues related to targeted delivery, stability, and solubility as well as to potentiate therapeutic and clinical implication, the nanodelivery systems have gained remarkable recognition. Therefore, this study was aimed to encapsulate BMV into the chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. The prepared NPs were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, loading capacity, crystallinity, thermal behavior, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimized BMV-CS-NPs exhibited optimum physicochemical characteristics including small particle size (< 250 ± 28 nm), higher zeta potential (+58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that BMV-CS-NPs displayed Fickian-diffusion type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency and the amount of BMV retained into the epidermis and the dermis were comparatively higher in case of BMV-CS-NPs compared to BMV solution. Conclusively, we anticipated that BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.
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.
New developments and clinical transition of hyaluronic acid-based nanotherapeutics for treatment of cancer: reversing multidrug resistance, tumour-specific targetability and improved anticancer efficacy

Safdar MH, Hussain Z, Abourehab MAS, Hasan H, Afzal S, Thu HE

Artif Cells Nanomed Biotechnol, 2018 Dec;46(8):1967-1980.
PMID: 29082766 DOI: 10.1080/21691401.2017.1397001

This review aims to overview and critically analyses recent developments in achieving tumour-specific delivery of anticancer agents, maximizing anticancer efficacy, and mitigating tumour progression and off-target effects. Stemming from critical needs to develop target-specific delivery vehicles in cancer therapy, various hyaluronic acid (HA)-conjugated nanomedicines have been fabricated owing to their biocompatibility, safety, tumour-specific targetability of drugs and genes, and proficient interaction with cluster-determinant-44 (CD44) receptors over-expressed on the surface of tumour cells. HA-based conjugation or surface modulation of anticancer drugs encapsulated nanocarriers have shown promising efficacy against the various types of carcinomas of liver, breast, colorectal, pancreatic, lung, skin, ovarian, cervical, head and neck and gastric. The success of this emerging platform is assessed in achieving the rapid internalization of anticancer payloads into the tumour cells, impeding cancer cells division and proliferation, induction of cancer-specific apoptosis and prevention of metastasis (tumour progression). This review extends detailed insight into the engineering of HA-based nanomedicines, characterization, utilization for the diagnosis or treatment of CD44 over-expressing cancer subtypes and emphasizing the transition of nanomedicines to clinical cancer therapy.
A stable hydrocortisone nanosuspension for improved dissolution: Preparation, characterization and in vitro evaluation

Ali HS, Khan S, York P, Shah SM, Khan J, Hussain Z, et al.

Pak J Pharm Sci, 2017 Sep;30(5):1635-1643.
PMID: 29084684

Drug nanosuspensions have gained tremendous attraction as a platform in drug delivery. In the present work, a nanosuspension was prepared by a wet milling approach in order to increase saturation solubility and dissolution of the water insoluble drug, hydrocortisone. Size of the generated particeles was 290 nm ± 9 nm having a zeta potential of -1.9 mV ± 0.6 mV. Nanosized particles were found to have a rod shape with a narrow particle size distribution (PDI =0.17). Results of differential scanning calorimetry and X-ray diffraction analyses revealed minor modifications of crystallinity of hydrocortisone following the milling process. Solubility of hydrocortisone was enhanced by nanonization to 875µg/ml ±2.5, an almost 2.9-fold compared to the raw hydrocortisone. Moreover, the nanosuspension formulation substabtially enhanced the dissolution rate of hydrocortisone where >97% of the hydrocortisone was dissolved within 10 minutes opposed to 22.3% for the raw 50% for the raw hydrocortisone and the commercial tablet, respectively. The bioavailability study resulted in AUC 0-9h for HC nanosuspensions (31.50±2.50), which is significantly (p<0.05) higher compared to the AUC 0-9h (14.85±3.25) resulted for HC solution. The nanosuspension was physically stable at room temperature for 24 months.
Hyaluronic acid-modified betamethasone encapsulated polymeric nanoparticles: fabrication, characterisation, in vitro release kinetics, and dermal targeting

Pandey M, Choudhury H, Gunasegaran TAP, Nathan SS, Md S, Gorain B, et al.

Drug Deliv Transl Res, 2019 04;9(2):520-533.
PMID: 29488170 DOI: 10.1007/s13346-018-0480-1

Atopic dermatitis (AD) is a chronically relapsing eczematous skin disease characterised by frequent episodes of rashes, severe flares, and inflammation. Till date, there is no absolute therapy for the treatment of AD; however, topical corticosteroids (TCs) are the majorly prescribed class of drugs for the management of AD in both adults and children. Though, topical route is most preferable; however, limited penetration of therapeutics across the startum cornum (SC) is one of the major challenges for scientists. Therefore, the present study was attempted to fabricate a moderate-potency TC, betamethasone valerate (BMV), in the form of chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. To further improve the targeting efficiency of BMV and to potentiate its therapeutic efficacy, the fabricated BMV-CS-NPs were coated with hyaluronic acid (HA). The prepared NPs were characterised for particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, loading capacity, crystallinity, thermal behaviour, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimised HA-BMV-CS-NPs exhibited optimum physicochemical characteristics including finest particle size (
Thermoresponsive curcumin/DsiRNA nanoparticle gels for the treatment of diabetic wounds: synthesis and drug release

Katas H, Wen CY, Siddique MI, Hussain Z, Mohd Fadhil FH

Ther Deliv, 2017 01;8(3):137-150.
PMID: 28145827 DOI: 10.4155/tde-2016-0075

AIM: Chitosan (CS) has been extensively studied as drug delivery systems for wound healing. Results/methodology: CS nanoparticles were loaded with curcumin (Cur) and DsiRNA against prostaglandin transporter gene and they were incorporated into 20 and 25% w/v Pluronic F-127. The gels were later analyzed for their rheology, gelation temperature (Tgel), morphology, drug incorporation and in vitro drug release. The particle size was in the range of 231 ± 17-320 ± 20 nm, depending on CS concentration. The gels had Tgel of 23-28°C and exhibited sustained drug release with high accumulated amount of drugs over 48 h.
CONCLUSION: A thermo-sensitive gel containing Cur/DsiRNA CS nanoparticles was successfully developed and has a great potential to be further developed.
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
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.
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 Pharmacoeconomic evaluation and burden of illness of acute exacerbation of COPD in patients in Malaysia. [Abstract]

Iqbal MS, Iqbal MZ, Barua A, Veettil SK, Wei LY, Kit LW, et al.

Value Health, 2014 Nov;17(7):A594.
PMID: 27202037 DOI: 10.1016/j.jval.2014.08.2046

OBJECTIVES. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) appears to be the main reason of hospitalization in COPD patients. Since substantial economic burden of COPD have not been previously studied in Malaysia, this study aimed at estimating and identifying different costs and related burden of illness in patients receiving treatment of AECOPD in a tertiary care hospital in Malaysia.
METHODS. A prospective follow-up study was performed in Department of Accident and Emergency and Respiratory Medicine of the hospital. Data were derived on the basis of per exacerbation episode. Relationship between direct medical costs and disease severity was analyzed using various descriptive and inferential statistical approaches.
RESULTS. Median actual direct medical costs and out-of-pocket costs were RM 457.68 (US$ 141.97) and RM 28.25 (US$ 8.76) per exacerbation respectively. Drug cost (41%) was the leading cost driver, followed by unit cost of treatment per bed (33.6%) and lab investigation cost (25.4%). However, food cost (44.2%) represented the largest proportion in out-of-pocket costs. More than 90% of actual direct medical costs were supported by the Government of Malaysia in the patients studied.
CONCLUSIONS. Impacts of AECOPD in health care resources are worthy of attention. Cost information from pharmacoeconomic studies is important in decision making for health care professionals and policy makers in order to improve health care outcome and minimize costs.
Fulltext Pharmacoeconomic evaluation of acute exacerbation of asthma in patients in Malaysia. [Abstract]

Iqbal MS, Iqbal MZ, Barua A, Veettil SK, Ling TK, Yong NB, et al.

Value Health, 2014 Nov;17(7):A594.
PMID: 27202038 DOI: 10.1016/j.jval.2014.08.2045

Objectives: The cost of acute exacerbations of asthma had not been well studied in literature. The aim of this study was to identify and quantify the (average) cost of moderate and severe exacerbations of asthma in patients attending tertiary-care setup in Malaysia. The related burden of exacerbations was also calculated.
Methods: The costs including lab investigation charges, unit costs of treatment per bed, medication charges, food costs, transportation costs and loss of productivity were calculated per asthma episode. Data was analysed by Statistical Package for the Social Sciences (SPSS) version 18.0 using various descriptive and inferential statistical tests.
Results: A median medical cost of acute exacerbation of asthma under Ministry of Health’s (MOH) perspective was USD 105.00 (RM338.47) per episode. Medication cost comprised the majority (52.38%) of the total medical costs. A median medical cost of acute exacerbation of asthma under patient’s perspective was USD 1.55 (RM4.99) per episode. ConclusionsAsthma exacerbation and length of stay in the hospital were proportional to the direct medical costs. In Malaysia, a substantial proportion of the direct medical cost of asthma treatment is heavily subsidised for the locals.
Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation

Zha GF, Zhang CP, Qin HL, Jantan I, Sher M, Amjad MW, et al.

Bioorg Med Chem, 2016 05 15;24(10):2352-9.
PMID: 27083471 DOI: 10.1016/j.bmc.2016.04.015

A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.

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