Displaying publications 21 - 40 of 69 in total

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  1. Gorain B, Rajeswary DC, Pandey M, Kesharwani P, Kumbhar SA, Choudhury H
    Curr Pharm Des, 2020;26(19):2233-2246.
    PMID: 32167424 DOI: 10.2174/1381612826666200313125613
    Increasing incidence of demented patients around the globe with limited FDA approved conventional therapies requires pronounced research attention for the management of the demented conditions in the growing elderly population in the developing world. Dementia of Alzheimer's type is a neurodegenerative disorder, where conventional therapies are available for symptomatic treatment of the disease but possess several peripheral toxicities due to lack of brain targeting. Nanotechnology based formulations via intranasal (IN) routes of administration have shown to improve therapeutic efficacy of several therapeutics via circumventing blood-brain barrier and limited peripheral exposure. Instead of numerous research on polymeric and lipid-based nanocarriers in the improvement of therapeutic chemicals and peptides in preclinical research, a step towards clinical studies still requires wide-ranging data on safety and efficacy. This review has focused on current approaches of nanocarrierbased therapies on Alzheimer's disease (AD) via the IN route for polymeric and lipid-based nanocarriers for the improvement of therapeutic efficacy and safety. Moreover, the clinical application of IN nanocarrier-based delivery of therapeutics to the brain needs a long run; however, proper attention towards AD therapy via this platform could bring a new era for the AD patients.
  2. Yap PR, Goh KL
    Curr Pharm Des, 2015;21(35):5073-81.
    PMID: 26369685
    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed group of drugs in the world. They are used primarily for pain relief in chronic inflammatory joint disease and act by inhibiting enzymes COX1 and COX2 and ultimately preventing the production of active prostanoids which are required for the innate inflammatory pathway. The use of NSAIDs have been associated with the development of gastrointestinal (GI) symptoms ranging from simple dyspepsia to life threatening GI bleeds and perforations. The definition of dyspepsia has evolved over the years and this has hampered accurate studies on the prevalence of dyspepsia as different studies used varying criteria to define dyspepsia. It is now known that NSAIDs significantly increase the risk of dyspepsia.The risk of developing peptic ulcer disease vary with specific NSAIDs and dosages but there is no correlation between the symptoms of dyspepsia and underlying peptic ulcers. The pathogenesis of dyspepsia with NSAIDs is not completely understood. Peptic ulceration alone is not able to account for the majority of dyspepsia symptoms encountered by NSAIDs users. Erosive oesophagitis secondary to NSAIDs may be contributing factor to the prevalence of dyspepsia in NSAIDs users. Altered gut permeability and changes in gastric mechanosensory function due to NSAIDs may also be a contributory factor. Management of NSAID induced dyspepsia is involves a multipronged approach. Drug avoidance if possible would be ideal. Other options include using the lowest effective dose, changing to an NSAIDs with a safer GI risk profile, avoiding concurrent use with other NSAIDs or if the patient has a previous history of peptic ulcer disease, and co-prescribing with anti-secretory medications such as proton pump inhibitors. Eradication of Helicobacter pylori has a protective role against developing peptic ulcers and may also improve symptoms of NSAIDs induced dyspepsia.
  3. Islam MA, Alam F, Khalil MI, Sasongko TH, Gan SH
    Curr Pharm Des, 2016;22(20):2926-46.
    PMID: 26951101
    Globally, thrombosis-associated disorders are one of the main contributors to fatalities. Besides genetic influences, there are some acquired and environmental risk factors dominating thrombotic diseases. Although standard regimens have been used for a long time, many side effects still occur which can be life threatening. Therefore, natural products are good alternatives. Although the quest for antithrombotic natural products came to light only since the end of last century, in the last two decades, a considerable number of natural products showing antithrombotic activities (antiplatelet, anticoagulant and fibrinolytic) with no or minimal side effects have been reported. In this review, several natural products used as antithrombotic agents including medicinal plants, vegetables, fruits, spices and edible mushrooms which have been discovered in the last 15 years and their target sites (thrombogenic components, factors and thrombotic pathways) are described. In addition, the side effects, limitations and interactions of standard regimens with natural products are also discussed. The active compounds could serve as potential sources for future research on antithrombotic drug development. As a future direction, more advanced researches (in quest of the target cofactor or component involved in antithrombotic pathways) are warranted for the development of potential natural antithrombotic medications (alone or combined with standard regimens) to ensure maximum safety and efficacy.
  4. Sharma PA, Maheshwari R, Tekade M, Tekade RK
    Curr Pharm Des, 2015;21(30):4465-78.
    PMID: 26354926
    The increasing prevalence and complexity of cardiovascular diseases demand innovative strategies for diagnostic and therapeutic applications to improve patient care/prognoses. Additionally, various factors constrain present cardiovascular therapies, including low aqueous drug solubility, early metabolism, short half-life and drug delivery limitations. The efficient treatment of cardiovascular diseases requires improvement of traditional drug delivery systems. This can be accomplished by using novel nanomaterial that can incorporate diverse bio-actives along with diagnostic agents in a single carrier, referred to as theranostics. This review discusses the state of the art in the applications to diagnosis and therapy of innovative, nanomaterial- based strategies such as lipid based carriers, nanocapsules, magnetic nanoparticles, gold nanoparticles, protein conjugated nanoparticles, dendrimers and carbon-based nanoformulations with a special emphasis on how they can contribute to improving the management of cardiovascular disease.
  5. Khan NR, Harun MS, Nawaz A, Harjoh N, Wong TW
    Curr Pharm Des, 2015;21(20):2848-66.
    PMID: 25925113
    Transdermal drug delivery is impeded by the natural barrier of epidermis namely stratum corneum. This limits the route to transport of drugs with a log octanol-water partition coefficient of 1 to 3, molecular weight of less than 500 Da and melting point of less than 200°C. Nanotechnology has received widespread investigation as nanocarriers are deemed to be able to fluidize the stratum corneum as a function of size, shape, surface charges, and hydrophilicity-hydrophobicity balance, while delivering drugs across the skin barrier. This review provides an overview and update on the latest designs of liposomes, ethosomes, transfersomes, niosomes, magnetosomes, oilin- water nanoemulsions, water-in-oil nanoemulsions, bicontinuous nanoemulsions, covalently crosslinked polysaccharide nanoparticles, ionically crosslinked polysaccharide nanoparticles, polyelectrolyte coacervated nanoparticles and hydrophobically modified polysaccharide nanoparticles with respect to their ability to fuse or fluidize lipid/protein/tight junction regimes of skin, and effect changes in skin permeability and drug flux. Universal relationships of nanocarrier size, zeta potential and chemical composition on transdermal permeation characteristics of drugs will be developed and discussed.
  6. Maheshwari R, Tekade M, Sharma PA, Tekade RK
    Curr Pharm Des, 2015;21(30):4427-40.
    PMID: 26471319
    Cardiovascular diseases (CVDs), primarily myocardial infarction (MI), atherosclerosis, hypertension and congestive heart failure symbolize the foremost cause of death in almost all parts of the world. Besides the traditional therapeutic approaches for the management of CVDs, newer innovative strategies are also emerging on the horizon. Recently, gene silencing via small interfering RNA (siRNA) is one of the hot topics amongst various strategies involved in the management of CVDs. The siRNA mechanism involves natural catalytic processes to silence pathological genes that are overexpressed in a particular disease. Also the versatility of gene expression by siRNA deciphers a prospective tactic to down-regulate diseases associated gene, protein or receptor existing on a specific disease target. This article reviews the application of siRNA against CVDs with special emphasis on gene targets in combination with delivery systems such as cationic hydrogels, polyplexes, peptides, liposomes and dendrimers.
  7. Gorain B, Al-Dhubiab BE, Nair A, Kesharwani P, Pandey M, Choudhury H
    Curr Pharm Des, 2021;27(43):4404-4415.
    PMID: 34459377 DOI: 10.2174/1381612827666210830095941
    The advancement of delivery tools for therapeutic agents has brought several novel formulations with increased drug loading, sustained release, targeted delivery, and prolonged efficacy. Amongst the several novel delivery approaches, multivesicular liposome has gained potential interest because this delivery system possesses the above advantages. In addition, this multivesicular liposomal delivery prevents degradation of the entrapped drug within the physiological environment while administered. The special structure of the vesicles allowed successful entrapment of hydrophobic and hydrophilic therapeutic agents, including proteins and peptides. Furthermore, this novel formulation could maintain the desired drug concentration in the plasma for a prolonged period, which helps to reduce the dosing frequencies, improve bioavailability, and safety. This tool could also provide stability of the formulation, and finally gaining patient compliance. Several multivesicular liposomes received approval for clinical research, while others are at different stages of laboratory research. In this review, we have focused on the preparation of multivesicular liposomes along with their application in different ailments for the improvement of the performance of the entrapped drug. Moreover, the challenges of delivering multivesicular vesicles have also been emphasized. Overall, it could be inferred that multivesicular liposomal delivery is a platform of advanced drug delivery with improved efficacy and safety.
  8. 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.

  9. Mahmod Al-Qattan MN, Mordi MN
    Curr Pharm Des, 2019;25(7):817-831.
    PMID: 30834826 DOI: 10.2174/1381612825666190304122624
    Modulating cellular processes through extracellular chemical stimuli is medicinally an attractive approach to control disease conditions. GPCRs are the most important group of transmembranal receptors that produce different patterns of activations using intracellular mediators (such as G-proteins and Beta-arrestins). Adenosine receptors (ARs) belong to GPCR class and are divided into A1AR, A2AAR, A2BAR and A3AR. ARs control different physiological activities thus considered valuable target to control neural, heart, inflammatory and other metabolic disorders. Targeting ARs using small molecules essentially works by binding orthosteric and/or allosteric sites of the receptors. Although targeting orthosteric site is considered typical to modulate receptor activity, allosteric sites provide better subtype selectivity, saturable modulation of activity and variable activation patterns. Each receptor exists in dynamical equilibrium between conformational ensembles. The equilibrium is affected by receptor interaction with other molecules. Changing the population of conformational ensembles of the receptor is the method by which orthosteric, allosteric and other cellular components control receptor signaling. Herein, the interactions of ARs with orthosteric, allosteric ligands as well as intracellular mediators are described. A quinary interaction model for the receptor is proposed and energy wells for major conformational ensembles are retrieved.
  10. Pandey M, Ting JSS, Gorain B, Jain N, Mayuren J
    Curr Pharm Des, 2023;29(40):3254-3262.
    PMID: 37438899 DOI: 10.2174/1381612829666230712162540
    The prevalence of vaginal infection is increasing among women, especially at reproductive age. For proper eradication of infection, the effective concentration of a drug is required at the infection site. Therefore, local delivery is recommended to exert a direct therapeutic effect at the site action that causes a reduction in dose and side effects. The main focus of vaginal drug delivery is to enhance retention time and patient compliance. The high recurrence rate of vaginal infection due to the lack of effective treatment strategies opens the door for new therapeutic approaches. To combat these setbacks, intravaginal gene therapies have been investigated. High attention has been gained by vaginal gene therapy, especially for sexually transmitted infection treatment. Despite much research, no product is available in the market, although in vitro and preclinical data support the vaginal route as an effective route for gene administration. The main focus of this review is to discuss the recent advancement in miniaturized polymeric systems for intravaginal gene therapies to treat local infections. An overview of different barriers to vaginal delivery and challenges of vaginal infection treatment are also summarised.
  11. Kumar M, Kumar D, Chopra S, Mahmood S, Bhatia A
    Curr Pharm Des, 2023;29(44):3532-3545.
    PMID: 38151837 DOI: 10.2174/0113816128282478231219044000
    BACKGROUND: Over the past ten years, tremendous progress has been made in microbubble-based research for a variety of biological applications. Microbubbles emerged as a compelling and dynamic tool in modern drug delivery systems. They are employed to deliver drugs or genes to targeted regions of interest, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials.

    OBJECTIVE: The objective of this article is to review the microbubble compositions and physiochemical characteristics in relation to the development of innovative biomedical applications, with a focus on molecular imaging and targeted drug/gene delivery.

    METHODS: The microbubbles are prepared by using various methods, which include cross-linking polymerization, emulsion solvent evaporation, atomization, and reconstitution. In cross-linking polymerization, a fine foam of the polymer is formed, which serves as a bubble coating agent and colloidal stabilizer, resulting from the vigorous stirring of a polymeric solution. In the case of emulsion solvent evaporation, there are two solutions utilized in the production of microbubbles. In atomization and reconstitution, porous spheres are created by atomising a surfactant solution into a hot gas. They are encapsulated in primary modifier gas. After the addition of the second gas or gas osmotic agent, the package is placed into a vial and sealed after reconstituting with sterile saline solution.

    RESULTS: Microbubble-based drug delivery is an innovative approach in the field of drug delivery that utilizes microbubbles, which are tiny gas-filled bubbles, act as carriers for therapeutic agents. These microbubbles can be loaded with drugs, imaging agents, or genes and then guided to specific target sites.

    CONCLUSION: The potential utility of microbubbles in biomedical applications is continually growing as novel formulations and methods. The versatility of microbubbles allows for customization, tailoring the delivery system to various medical applications, including cancer therapy, cardiovascular treatments, and gene therapy.

  12. Rezayi M, Farjami Z, Hosseini ZS, Ebrahimi N, Abouzari-Lotf E
    Curr Pharm Des, 2018;24(39):4675-4680.
    PMID: 30636591 DOI: 10.2174/1381612825666190111144525
    Small noncoding microRNAs (miRNAs) are known as noninvasive biomarkers for early detection in various cancers. In fact, miRNAs have key roles in carcinogenicity process such as proliferation, apoptosis and metastasis. After cardiovascular disease, cancer is the second cause of death in the world with an estimated 9.6 million deaths in 2018. So, early diagnosis of cancer is critical for successful treatment. To date, several selective and sensitive laboratory-based methods have been applied for the detection of circulating miRNA, but a simple, short assay time and low-cost method such as a biosensor method as an alternative approach to monitor cancer biomarker is required. In this review, we have highlighted recent advances in biosensors for circulating miRNA detection.
  13. Alam F, Islam MA, Khalil MI, Gan SH
    Curr Pharm Des, 2016;22(20):3034-49.
    PMID: 26951104 DOI: 10.2174/1381612822666160307145801
    Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is characterized by insulin resistance in the hepatic and peripheral tissues. Glucose transporter 4 (GLUT4) plays a major role in the pathophysiology of T2DM. Its defective expression or translocation to the peripheral cell plasma membrane in T2DM patients hinders the entrance of glucose into the cell for energy production. In addition to suitable drugs, an appropriate diet and/or exercise can be implemented to target the increase in GLUT4 expression, GLUT4 concentrations and GLUT4 translocation to the cell surface when managing the glucose metabolism of T2DM patients. In this review, we discussed successful intervention strategies that were individually administered or coupled with diet and/or exercise and affected the expression and translocation of GLUT4 in T2DM while reducing the excess glucose load from the blood. Additionally, some potentially good synthetic and natural compounds, which can activate the insulin-independent GLUT4 signaling pathways for the efficient management of T2DM, are highlighted as possible targets or emerging alternative sources for future anti-diabetic drug development.
  14. Bjørklund G, Cruz-Martins N, Goh BH, Mykhailenko O, Lysiuk R, Shanaida M, et al.
    Curr Pharm Des, 2023 Aug 09.
    PMID: 37559241 DOI: 10.2174/1381612829666230809094242
    The average worldwide human life expectancy is 70 years, with a significantly higher value in Western societies. Many modern diseases are not associated with premature mortality but with a decreased quality of life in aged patients and an excessive accumulation of various toxic compounds in the human body during life. Today, scientists are especially interested in finding compounds that can help increase a healthy lifespan by detoxifying the body. Phytotherapy with specific approaches is used in alternative medicine to remove toxins from the body. Worldwide, research is conducted to identify medicinal plant-derived molecules that, with few or no side effects, may protect the liver and other organs. This review provides updated information about the detoxification process, the traditional and modern use of the most effective medicinal plants, their active metabolites as detoxifying agents, and the mechanisms and pathways involved in the detoxification process. Among medicinal plants with substantial detoxifying properties, a major part belongs to the Asteraceae family (Silybum marianum, Cynara scolymus, Arctium lappa, Helichrysum spp, Inula helenium, and Taraxacum officinale). The most widely used hepatoprotective phytocomponent is silymarin, a standardized extract from the Silybum marianum seeds containing a mixture of flavonolignans. Many polysaccharides, polyphenols, and terpenoids have a detoxifying effect. Overall, scientific data on medicinal plants used in phytotherapeutic practice worldwide provides an understanding and awareness of their efficacy in detoxification.
  15. Shukla MK, Dubey A, Pandey S, Singh SK, Gupta G, Prasher P, et al.
    Curr Pharm Des, 2022;28(39):3202-3211.
    PMID: 35422206 DOI: 10.2174/1381612828666220413103831
    Several factors exist that limit the efficacy of lung cancer treatment. These may be tumor-specific delivery of therapeutics, airway geometry, humidity, clearance mechanisms, presence of lung diseases, and therapy against tumor cell resistance. Advancements in drug delivery using nanotechnology based multifunctional nanocarriers, have emerged as a viable method for treating lung cancer with more efficacy and fewer adverse effects. This review does a thorough and critical examination of effective nano-enabled approaches for lung cancer treatment, such as nano-assisted drug delivery systems. In addition, to therapeutic effectiveness, researchers have been working to determine several strategies to produce nanotherapeutics by adjusting the size, drug loading, transport, and retention. Personalized lung tumor therapies using sophisticated nano modalities have the potential to provide great therapeutic advantages based on individual unique genetic markers and disease profiles. Overall, this review provides comprehensive information on newer nanotechnological prospects for improving the management of apoptosis in lung cancer.
  16. Ansari MT, Ramlan TA, Jamaluddin NN, Zamri N, Salfi R, Khan A, et al.
    Curr Pharm Des, 2020;26(34):4272-4276.
    PMID: 32693760 DOI: 10.2174/1381612826666200720235752
    Cancer and tumor have been major reasons for numerous deaths in this century across the world. Many strategies have been designed to treat, diagnose, or prevent cancer. The success of chemotherapy largely depends on drug targeting. The advent of nanotechnology has vastly improved drug delivery for targeting and diagnosis. Nevertheless, the accuracy of drug targeting with polymeric nanoparticles has always been questionable. The polymeric nanoparticles synthesized from varieties of lipid-based compounds or combined with vectors, such as liposomes, ethosomes, and transfersomes, may allow the drug to overcome the issue of resistance to drug absorption in biological membranes. The combined effects of lipid-based nanocarriers are known to improve the efficacy and accuracy of polymeric nanoparticles. The present review explores the application of lipid based nanocarriers in the treatment and diagnosis of cancer A special focus is given to the use of lipid-based nanocarriers in the treatment, diagnosis, and mitigation of cancer located in blood, brain, lung, and colon. The treatment of these cancers has always been questionable as the chances of relapse are very high. The review encompasses the use of lipid-based nanocarriers in targeting tissue-specific cancer cells.
  17. Chow YL, Teh LK, Chyi LH, Lim LF, Yee CC, Wei LK
    Curr Pharm Des, 2020;26(34):4261-4271.
    PMID: 32534558 DOI: 10.2174/1381612826666200614180958
    Stroke is the second leading cause of death and a major cause of disability worldwide. Both modifiable and non-modifiable risk factors can affect the occurrence of ischemic stroke at varying degrees. Among them, atherosclerosis has been well-recognized as one of the main culprits for the rising incidence of stroke-related mortality. Hence, the current review aimed to summarize the prominent role of lipid metabolism genes such as PCSK9, ApoB, ApoA5, ApoC3, ApoE, and ABCA1 in mediating ischemic stroke occurrence.
  18. Mozar FS, Chowdhury EH
    Curr Pharm Des, 2018;24(28):3283-3296.
    PMID: 30062957 DOI: 10.2174/1381612824666180730161721
    PEG-functionalized nanoparticles as carriers of chemotherapeutics agents have been explored with notable successes in preclinical and clinical stages of cancer treatment, with some already approved by FDA, namely PEGylated liposomes and polymers. Half-life extension of therapeutic agents through PEGylation process improves their pharmacokinetic (PK) profiles, thereby reducing their dosing frequency. Protein corona composition of PEGylated nanoparticles (NPs) confers a tremendous influence on their surface characteristics which directly impact tumor accumulation and clearance properties of the drugs. By controlling the size and complexity of PEG molecules, as well as by attaching targeting moieties, the surface characteristics of NPs can be manipulated to improve their tumor uptake without sacrificing the circulation time. This review focuses on design and applications of PEGylated NPs for tumor targeted drug delivery in animal models and clinical setting.
  19. Lim TS, Chan SK
    Curr Pharm Des, 2016;22(43):6480-6489.
    PMID: 27669969 DOI: 10.2174/1381612822666160923111924
    BACKGROUND: Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries.

    METHODS: Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection.

    RESULTS: This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases.

    CONCLUSION: We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future.

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