Displaying publications 1 - 20 of 87 in total

Abstract:
Sort:
  1. Zhuo F, Abourehab MAS, Hussain Z
    Carbohydr Polym, 2018 Oct 01;197:478-489.
    PMID: 30007638 DOI: 10.1016/j.carbpol.2018.06.023
    Nano-delivery systems have gained remarkable recognition for targeted delivery of therapeutic payload, reduced off-target effects, and improved biopharmaceutical profiles of drugs. Therefore, we aimed to fabricate polymeric nanoparticles (NPs) to deliver tacrolimus (TCS) to deeper layers of the skin in order to alleviate its systemic toxicity and improved therapeutic efficacy against atopic dermatitis (AD). To further optimize the targeting efficiency, TCS-loaded NPs were coated with hyaluronic acid (HA). Following the various physicochemical optimizations, the prepared HA-TCS-CS-NPs were tested for in vitro drug release kinetics, drug permeation across the stratum corneum, percentage of drug retained in the epidermis and dermis, and anti-AD efficacy. Results revealed that HA-TCS-CS-NPs exhibit sustained release profile, promising drug permeation ability, improved skin retention, and pronounced anti-AD efficacy. Conclusively, we anticipated that HA-based modification of TCS-CS-NPs could be a promising therapeutic approach for rationalized management of AD, particularly in children as well as in adults having steroid phobia.
  2. Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019 Feb 14.
    PMID: 30767742 DOI: 10.2174/1389450120666190214141626
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess cerebrospinal fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, blurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of cerebrospinal fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

  3. Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019;20(10):1041-1057.
    PMID: 30767741 DOI: 10.2174/1389450120666190214121342
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess Cerebrospinal Fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, slurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

  4. 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.
  5. Tumpang MA, Ramli NA, Hussain Z
    Curr Drug Targets, 2018;19(6):674-700.
    PMID: 28914203 DOI: 10.2174/1389450118666170913162147
    BACKGROUND: Phytomedicines have been well-accepted alternative complementary therapies for the treatment of a wide range of acute and chronic skin inflammatory diseases including chronic herpes, prurigo, psoriasis, and atopic dermatitis (AD). A plethora of in vitro and in vivo studies have evidenced the therapeutic viability of phytomedicines, polyherbal formulations, plant-based materials and their decoctions for the treatment of mild-to-severe AD.

    OBJECTIVE: This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of phytomedicines for the treatment of AD and explore their anti-AD efficacy.

    RESULTS: The critical analysis of a wide algorithm of herbal medicines revealed that their remarkable anti-AD efficacy is attributed to their potential of reducing erythema intensity, oedema, inflammation, transepidermal water loss (TEWL) and a remarkable suppression of mRNA expression of ADassociated inflammatory biomarkers including histamine, immunoglobulin (Ig)-E, prostaglandins, mast cells infiltration and production of cytokines and chemokines in the serum and skin biopsies.

    CONCLUSION: In conclusion, herbal medicines hold great promise as complementary and alternative therapies for the treatment of mild-to-moderate AD when used as monotherapy and for the treatment of moderate-to-severe AD when used in conjunction with other pharmacological agents.

  6. Thu HE, Mohamed IN, Hussain Z, Shuid AN
    J Ethnopharmacol, 2017 Jan 04;195:143-158.
    PMID: 27818256 DOI: 10.1016/j.jep.2016.10.085
    ETHNOPHARMACOLOGICAL RELEVANCE: Eurycoma longifolia (EL) has been well-studied traditionally as a chief ingredient of many polyherbal formulations for the management of male osteoporosis. It has also been well-recognised to protect against bone calcium loss in orchidectomised rats.

    AIM OF THE STUDY: To evaluate the effects of EL on the time-mannered sequential proliferative, differentiative, and morphogenic modulation in osteoblasts compared with testosterone.

    MATERIALS AND METHODS: Cell proliferation was analysed using MTS assay and phase contrast microscopy. Osteogenic differentiation of MC3T3-E1 cells was assessed through a series of characteristic assays which include crystal violet staining, alkaline phosphatase (ALP) activity and Van Gieson staining. Taken together, the bone mineralization of extra cellular matrix (ECM) was estimated using alizarin red s (ARS) staining, von kossa staining, scanning electron microscopic (SEM) and energy dispersive x-ray (EDX) analysis.

    RESULTS: The cell proliferation data clearly revealed the efficiency of EL particularly at a dose of 25µg/mL, in improving the growth of MC3T3-E1 cells compared with the untreated cells. Data also showed the prominence of EL in significantly promoting ALP activity throughout the entire duration of treatment compared with the testosterone-treated cells. The osteogenic differentiation potential of EL was further explored by analysing mineralization data which revealed that the calcified nodule formation (calcium deposition) and phosphate deposition was more pronounced in cells treated with 25µg/mL concentration of EL at various time points compared with the untreated and testosterone treated cells. The scanning electron microscopic (SEM) analysis also revealed highest globular masses of mineral deposits (identified as white colour crystals) in the ECM of cultured cells treated with 25µg/mL concentration of EL.

    CONCLUSION: Compared to testosterone, greater potential of EL in promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells provides an in vitro basis for the prevention of male osteoporosis. Thus, we anticipate that EL can be considered as an alternative approach to testosterone replacement therapy (TRT) for the treatment of male osteoporosis.

  7. Thu HE, Hussain Z, Mohamed IN, Shuid AN
    Curr Drug Targets, 2018;19(10):1109-1126.
    PMID: 28721818 DOI: 10.2174/1389450118666170718151913
    BACKGROUND: Eurycoma longifolia is a well-documented herbal medicine that has gained widespread recognition due to its versatile pharmacological activities including anticancer, antimalarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, antirheumatism and anti-ulcer. Plethora of in vitro and in vivo studies evidenced their excellent antiproliferative and anticancer efficacy against various types of human cancers.

    OBJECTIVE: This review was aimed to critically analyze the therapeutic viability and anticancer efficacy of Eurycoma longifolia in the treatment of cancer and also to propose its molecular and translational mechanism of cytotoxicity against cancerous cells.

    RESULTS: Among a range of medicinally active compounds isolated from various parts (roots, stem, bark and leaves) of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Eurycomanone, one of the most active medicinal compounds of Eurycoma longifolia, displayed a strong dose-dependent anticancer efficacy against lung carcinoma (A-549 cells) and breast cancer (MCF-7 cells); however, showed moderate efficacy against gastric (MGC-803 cells) and intestinal carcinomas (HT-29 cells). The prime mode of cytotoxicity of Eurycoma longifolia and its medicinal compounds is the induction of apoptosis (programmed cell death) via the up-regulation of the expression of p53 (tumor suppressor protein) and pro-apoptotic protein (Bax) and downregulation of the expression of anti-apoptotic protein (Bcl-2). A remarkable alleviation in the mRNA expression of various cancer-associated biomarkers including heterogeneous nuclear ribonucleoprotein (hnRNP), prohibitin (PHB), annexin-1 (ANX1) and endoplasmic reticulum protein-28 (ERp28) has also been evidenced.

    CONCLUSION: Eurycoma longifolia and its medicinal constituents exhibit promising anticancer efficacy and thus can be considered as potential complementary therapy for the treatment of various types of human cancers.

  8. 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.
  9. Thu HE, Hussain Z, Mohamed IN, Shuid AN
    J Ayurveda Integr Med, 2018 08 16;10(2):102-110.
    PMID: 30120052 DOI: 10.1016/j.jaim.2017.07.014
    BACKGROUND: Eurycoma longifolia (E. longifolia) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Numerous in vivo studies have explored the effects of E. longifolia on osteoporosis; however, the in vitro cellular mechanism was not discovered yet.

    OBJECTIVES: The present study was aimed to investigate the effect of E. longifolia on the proliferation, differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model.

    MATERIALS AND METHODS: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measured to comprehend the mechanism of osteoclastogenesis.

    RESULTS: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7 cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed. Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activity was observed in E. longifolia treated cell cultures.

    CONCLUSION: We anticipated that E. longifolia that enhances bone regeneration on the one hand and suppresses osteoclast's maturation on the other hand may have great therapeutic value in treating osteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associated with bone loss.

  10. Thu HE, Mohamed IN, Hussain Z, Shuid AN
    Iran J Basic Med Sci, 2017 Aug;20(8):894-904.
    PMID: 29085581 DOI: 10.22038/IJBMS.2017.9111
    OBJECTIVES: The present study was aimed to evaluate the time-mannered and dose-dependent effects of 5α-dihydrotestosterone (5α-DHT) on the proliferation and differentiation of bone forming cells using MC3T3-E1 cells.

    MATERIALS AND METHODS: Cell proliferation was analyzed using MTS and phase contrast microscopic assays. Osteogenic differentiation was assessed through a series of in vitro experiments including crystal violet staining, alkaline phosphatase (ALP) activity, and Van Gieson (VG) staining. Taken together, the efficiency of bone mineralization was examined by using alizarin red s (ARS) staining, Von Kossa staining, scanning electron microscopy (SEM) and energy dispersive x-ray (EDX) analysis.

    RESULTS: The resulting data revealed that 5α-DHT exhibits promising potential particularly at a dose of 0.1 ng/ml, in promoting the growth of MC3T3-E1 cells compared to the control group (CN). Moreover, a significantly higher ALP activity was evident in the experimental group treated with 5α-DHT compared to the CN group at various time intervals. MC3T3-E1 cells treated with 5α-DHT also expressed a remarkably higher collagen deposition and mineralization (calcium and phosphate contents) compared to the CN group at various time intervals.

    CONCLUSION: Conclusively, we suggest that 5α-DHT exhibits outstanding potential of promoting proliferation and differentiation in osteoblasts which could be the in vitro basis for the efficacy of 5α-DHT in the treatment of androgen-deficient male osteoporosis.

  11. Thu HE, Mohamed IN, Hussain Z, Shuid AN
    J Ayurveda Integr Med, 2017 11 13;9(4):272-280.
    PMID: 29146110 DOI: 10.1016/j.jaim.2017.04.005
    BACKGROUND: Among the numerous well-documented medicinal herbs, Eurycoma longifolia (EL) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Though numerous animal studies have explored the bone-forming capacity of EL, the exact mechanism was yet to be explored.

    OBJECTIVE(S): The present study was aimed to investigate the mechanism of bone-forming capacity of EL using MC3T3-E1 as an in vitro osteoblastic model.

    MATERIALS AND METHODS: The cell differentiation capacity of EL was investigated by evaluating cell growth, alkaline phosphatase (ALP) activity, collagen deposition and mineralization. Taken together, time-mannered expression of bone-related mediators which include bone morphogenic protein-2 (BMP-2), ALP, runt-related transcription factor-2 (Runx-2), osteocalcin (OCN), type I collagen, osteopontin (OPN), transforming growth factor-β1 (TGF-β1) and androgen receptor (AR) were measured to comprehend bone-forming mechanism of EL.

    RESULTS: Results demonstrated a superior cell differentiation efficacy of EL (particularly at a dose of 25 μg/mL) that was evidenced by dramatically increased cell growth, higher ALP activity, collagen deposition and mineralization compared to the testosterone. Results analysis of the bone-related protein biomarkers indicated that the expression of these mediators was well-regulated in EL-treated cell cultures compared to the control groups. These findings revealed potential molecular mechanism of EL for the prevention and treatment of male osteoporosis.

    CONCLUSION: The resulting data suggested that EL exhibited superior efficacy in stimulating bone formation via up-regulating the expression of various mitogenic proteins and thus can be considered as a potential natural alternative therapy for the treatment of osteoporosis.

  12. Thu HE, Hussain Z, Mohamed IN, Shuid AN
    Curr Drug Targets, 2018;19(14):1657-1671.
    PMID: 29468964 DOI: 10.2174/1389450119666180219123815
    BACKGROUND: Eurycoma longifolia (E. longifolia) has gained widespread recognition due to its versatile pharmacological activities including aphrodisiac, anticancer, antimicrobial, antioxidant, anti-inflammatory, anxiolytic, anti-diabetic, ergogenic, insecticidal, anti-rheumatism, bone protection, and anti-ulcer effects.

    OBJECTIVE: This review was aimed to critically overview the literature and summarizes the antibacterial, antiprotozoal, and antifungal trends of E. longifolia and its medicinally active components.

    RESULTS: Besides its well-documented safety, efficacy, and tolerability, a plethora of in vitro, in vivo, and human clinical studies has evidenced the antimicrobial efficacy of E. longifolia and its bioactive constituents. Phytochemical screening of various types of extracts (methanolic, ethyl acetate, and nbutanolic) from different parts (roots, stem, and leaves) of E. longifolia displayed a dose-dependent antibacterial, antiprotozoal, and antifungal responses. Comparative analysis revealed that the root extract of E. longifolia exhibited the highest antimicrobial efficacy compared to other parts of the plant. Bioactivity-guided fractionation identified that among all of the medicinal compounds isolated/ extracted from different parts of E. longifolia, eurycomanone displayed the strongest antibacterial, antiprotozoal and antifungal activities.

    CONCLUSION: Based on the critical analysis of the literature, we identified that E. longifolia exhibits promising antibacterial, antiprotozoal, and antifungal efficacies against various pathogenic microbes and thus can be considered as a potential complementary and alternative antimicrobial therapy.

  13. 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.
  14. Shao M, Hussain Z, Thu HE, Khan S, Katas H, Ahmed TA, et al.
    Colloids Surf B Biointerfaces, 2016 Nov 01;147:475-491.
    PMID: 27592075 DOI: 10.1016/j.colsurfb.2016.08.027
    Atopic dermatitis (AD) is a chronically relapsing skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin-E (IgE), T-lymphocytes and mast cells. The key pathophysiological factors causing this disease are immunological disorders and the compromised epidermal barrier integrity. Pruritus, intense itching, psychological stress, deprived physical and mental performance and sleep disturbance are the hallmark features of this dermatological complication. Preventive interventions which include educational programs, avoidance of allergens, exclusive care towards skin, and the rational selection of therapeutic regimen play key roles in the treatment of dermatosis. In last two decades, it is evident from a plethora of studies that scientific focus is being driven from conventional therapies to the advanced nanocarrier-based regimen for an effective management of AD. These nanocarriers which include polymeric nanoparticles (NPs), hydrogel NPs, liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanoemulsion, provide efficient roles for the target specific delivery of the therapeutic payload. The success of these targeted therapies is due to their pharmaceutical versatility, longer retention time at the target site, avoiding off-target effects and preventing premature degradation of the incorporated drugs. The present review was therefore aimed to summarise convincing evidence for the therapeutic superiority of advanced nanocarrier-mediated strategies over the conventional therapies used in the treatment of AD.
  15. Shao M, Hussain Z, Thu HE, Khan S, de Matas M, Silkstone V, et al.
    Crit Rev Ther Drug Carrier Syst, 2017;34(5):387-452.
    PMID: 29256838 DOI: 10.1615/CritRevTherDrugCarrierSyst.2017016957
    Chronic wounds which include diabetic foot ulcer (DFU), pressure ulcer, and arterial or venous ulcers compel a significant burden to the patients, healthcare providers, and the healthcare system. Chronic wounds are characterized by an excessive persistent inflammatory phase, prolonged infection, and the failure of defense cells to respond to environmental stimuli. Unlike acute wounds, chronic nonhealing wounds pose a substantial challenge to conventional wound dressings, and the development of novel and advanced wound healing modalities is needed. Toward this end, numerous conventional wound-healing modalities have been evaluated in the management of nonhealing wounds, but a multifaceted approach is lacking. Therefore, this review aims to compile and explore the wide therapeutic algorithm of current and advanced wound healing approaches to the treatment of chronic wounds. The algorithm of chronic wound healing techniques includes conventional wound dressings; approaches based on autografts, allografts, and cultured epithelial autografts; and recent modalities based on natural, modified or synthetic polymers and biomaterials, processed mutually in the form of hydrogels, films, hydrocolloids, and foams. Moreover, this review also explores the promising potential of advanced drug delivery systems for the sustained delivery of growth factors, curcumin, aloe vera, hyaluronic acid, and other bioactive substances as well as stem cell therapy. The current review summarizes the convincing evidence for the clinical dominance of polymer-based chronic wound healing modalities as well as the latest and innovative therapeutic strategies for the treatment of chronic wounds.
  16. Shah SM, Ullah F, Khan S, Shah SM, de Matas M, Hussain Z, et al.
    Drug Des Devel Ther, 2016;10:3837-3850.
    PMID: 27920499
    Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena(®) DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C-8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena(®) DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.
  17. 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.
  18. 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.
  19. 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.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links