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Displaying publications 61 - 69 of 69 in total

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Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery

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.
Calixarene: A Versatile Material for Drug Design and Applications

Hussain MA, Ashraf MU, Muhammad G, Tahir MN, Bukhari SNA

Curr Pharm Des, 2017;23(16):2377-2388.
PMID: 27779081 DOI: 10.2174/1381612822666160928143328

The therapy of various diseases by the drugs entrapped in calixarene derivatives is gaining attraction of researchers nowadays. Calixarenes are macrocyclic nano-baskets which belong to cavitands class of host-guest chemistry. They are the marvelous hosts with distinct hydrophobic three dimensional cavities to entrap and encapsulate biologically active guest drugs. Calixarene and its derivatives develop inclusion complexes with various types of drugs and vitamins for their sustained/targeted release. Calixarene and its derivatives are used as carriers for anti-cancer, anti-convulsant, anti-hypertensive, anthelmentic, anti-inflammatory, antimicrobial and antipsychotic drugs. They are the important biocompatible receptors to improve solubility, chemical reactivity and decrease cytotoxicity of poorly soluble drugs in supramolecular chemistry. This review focuses on the calixarene and its derivatives as the state-of-the-art in host-guest interactions for important drugs. We have also critically evaluated calixarenes for the development of prodrugs.
Adenosine Receptors as Novel Targets for the Treatment of Various Cancers

Gorain B, Choudhury H, Yee GS, Bhattamisra SK

Curr Pharm Des, 2019;25(26):2828-2841.
PMID: 31333092 DOI: 10.2174/1381612825666190716102037

Adenosine is a ubiquitous signaling nucleoside molecule, released from different cells within the body to act on vasculature and immunoescape. The physiological action on the proliferation of tumour cell has been reported by the presence of high concentration of adenosine within the tumour microenvironment, which results in the progression of the tumour, even leading to metastases. The activity of adenosine exclusively depends upon the interaction with four subtypes of heterodimeric G-protein-coupled adenosine receptors (AR), A1, A2A, A2B, and A3-ARs on the cell surface. Research evidence supports that the activation of those receptors via specific agonist or antagonist can modulate the proliferation of tumour cells. The first category of AR, A1 is known to play an antitumour activity via tumour-associated microglial cells to prevent the development of glioblastomas. A2AAR are found in melanoma, lung, and breast cancer cells, where tumour proliferation is stimulated due to inhibition of the immune response via inhibition of natural killer cells cytotoxicity, T cell activity, and tumourspecific CD4+/CD8+ activity. Alternatively, A2BAR helps in the development of tumour upon activation via upregulation of angiogenin factor in the microvascular endothelial cells, inhibition of MAPK and ERK 1/2 phosphorylation activity. Lastly, A3AR is expressed in low levels in normal cells whereas the expression is upregulated in tumour cells, however, agonists to this receptor inhibit tumour proliferation through modulation of Wnt and NF-κB signaling pathways. Several researchers are in search for potential agents to modulate the overexpressed ARs to control cancer. Active components of A2AAR antagonists and A3AR agonists have already entered in Phase-I clinical research to prove their safety in human. This review focused on novel research targets towards the prevention of cancer progression through stimulation of the overexpressed ARs with the hope to protect lives and advance human health.
Microbubbles: Revolutionizing Biomedical Applications with Tailored Therapeutic Precision

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.
Beneficiary and Adverse Effects of Phytoestrogens: A Potential Constituent of Plant-based Diet

Sridevi V, Naveen P, Karnam VS, Reddy PR, Arifullah M

Curr Pharm Des, 2021;27(6):802-815.
PMID: 32942973 DOI: 10.2174/1381612826999200917154747

BACKGROUND: Phytoestrogens are non-endocrine, non-steroidal secondary derivatives of plants and consumed through a plant-based diet also named as "dietary estrogens". The major sources of phytoestrogens are soy and soy-based foods, flaxseed, chickpeas, green beans, dairy products, etc. The dietary inclusion of phytoestrogen based foods plays a crucial role in the maintenance of metabolic syndrome cluster, including obesity, diabetes, blood pressure, cancer, inflammation, cardiovascular diseases, postmenopausal ailments and their complications. In recent days, phytoestrogens are the preferred molecules for hormone replacement therapy. On the other hand, they act as endocrine disruptors via estrogen receptor-mediated pathways. These effects are not restricted to adult males or females and identified even in development.
OBJECTIVE: Since phytoestrogenic occurrence is high at daily meals for most people worldwide, they focused to study for its beneficiary effects towards developing pharmaceutical drugs for treating various metabolic disorders by observing endocrine disruption.
CONCLUSION: The present review emphasizes the pros and cons of phytoestrogens on human health, which may help to direct the pharmaceutical industry to produce various phytoestrongen based drugs against various metabolic disorders.
Guest-host Relationship of Cyclodextrin and its Pharmacological Benefits

Alshati F, Alahmed TAA, Sami F, Ali MS, Majeed S, Murtuja S, et al.

Curr Pharm Des, 2023;29(36):2853-2866.
PMID: 37946351 DOI: 10.2174/0113816128266398231027100119

Many methods, including solid dispersion, micellization, and inclusion complexes, have been employed to increase the solubility of potent drugs. Beta-cyclodextrin (βCD) is a cyclic oligosaccharide consisting of seven glucopyranoside molecules, and is a widely used polymer for formulating soluble inclusion complexes of hydrophobic drugs. The enzymatic activity of Glycosyltransferase or α-amylase converts starch or its derivatives into a mixture of cyclodextrins. The βCD units are characterized by α -(1-4) glucopyranose bonds. Cyclodextrins possess certain properties that make them very distinctive because of their toroidal or truncated cage-like supramolecular configurations with multiple hydroxyl groups at each end. This allowed them to encapsulate hydrophobic compounds by forming inclusion complexes without losing their solubility in water. Chemical modifications and newer derivatives, such as methylated βCD, more soluble hydroxyl propyl methyl βCD, and sodium salts of sulfobutylether-βCD, known as dexolve® or captisol®, have envisaged the use of CDs in various pharmaceutical, medical, and cosmetic industries. The successful inclusion of drug complexes has demonstrated improved solubility, bioavailability, drug resistance reduction, targeting, and penetration across skin and brain tissues. This review encompasses the current applications of β-CDs in improving the disease outcomes of antimicrobials and antifungals as well as anticancer and anti-tubercular drugs.
Recent Advances in Non-Invasive Delivery of Macromolecules using Nanoparticulate Carriers System

Shadab M, Haque S, Sheshala R, Meng LW, Meka VS, Ali J

Curr Pharm Des, 2017;23(3):440-453.
PMID: 27784250 DOI: 10.2174/1381612822666161026163201

BACKGROUND: The drug delivery of macromolecules such as proteins and peptides has become an important area of research and represents the fastest expanding share of the market for human medicines. The most common method for delivering macromolecules is parenterally. However parenteral administration of some therapeutic macromolecules has not been effective because of their rapid clearance from the body. As a result, most macromolecules are only therapeutically useful after multiple injections, which causes poor compliance and systemic side effects.
METHOD: Therefore, there is a need to improve delivery of therapeutic macromolecules to enable non-invasive delivery routes, less frequent dosing through controlled-release drug delivery, and improved drug targeting to increase efficacy and reduce side effects.
RESULT: Non-invasive administration routes such as intranasal, pulmonary, transdermal, ocular and oral delivery have been attempted intensively by formulating macromolecules into nanoparticulate carriers system such as polymeric and lipidic nanoparticles.
CONCLUSION: This review discusses barriers to drug delivery and current formulation technologies to overcome the unfavorable properties of macromolecules via non-invasive delivery (mainly intranasal, pulmonary, transdermal oral and ocular) with a focus on nanoparticulate carrier systems. This review also provided a summary and discussion of recent data on non-invasive delivery of macromolecules using nanoparticulate formulations.
Current Status and Challenges in Rotigotine Delivery

Md S, Karim S, Saker SR, Gie OA, Hooi LC, Yee PH, et al.

Curr Pharm Des, 2020;26(19):2222-2232.
PMID: 32175832 DOI: 10.2174/1381612826666200316154300

Rotigotine is a non-ergoline, high lipophilic dopamine agonist. It is indicated as the first-line therapy for Parkinson's disease (PD) and Restless Leg Syndrome (RLS). However, the precise mechanism of rotigotine is yet to be known. Rotigotine has similar safety and tolerability to the other oral non-ergolinic dopamine antagonists in clinical trials, which include nausea, dizziness and somnolence. Neupro® was the first marketed transdermal patch formulation having rotigotine. The transdermal delivery system is advantageous as it enables continuous administration of the drug, thus providing steady-state plasma drug concentration for 24-hours. Intranasal administration of rotigotine allows the drug to bypass the blood-brain barrier enabling it to reach the central nervous system within minutes. Rotigotine can also be formulated as an extended-release microsphere for injection. Some challenges remain in other routes of rotigotine administration such as oral, parenteral and pulmonary, whereby resolving these challenges will be beneficial to patients as they are less invasive and comfortable in terms of administration. This review compiles recent work on rotigotine delivery, challenges and its future perspective.
MicroRNA-based Biosensors for Early Detection of Cancers

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.