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Two-dimensional projection of a monodendron with symmetrical branch junctures (i.e., Tomalia topologies) and Z = branch cell junctures with equal branch segments. Reprinted with permission from [28]. Copyright 1987 American Chemical Society.
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This article reviews progress over the past three decades related to the role of dendrimer-based, branch cell symmetry in the development of advanced drug delivery systems, aqueous based compatibilizers/solubilizers/excipients and nano-metal cluster catalysts. Historically, it begins with early unreported work by the Tomalia Group (i.e., The Dow Ch...
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During the past several decades, many sensing mechanisms have emerged, which provide new control strategies for designing closed-loop drug delivery systems. For such systems, numerous bioresponsive materials are utilized to construct functional modules for the desired devices. The typical closed-loop drug delivery systems recently reported in this...
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... Dendrimers are homogenous, branched, nanoscale structures with an inner core and an outside shell with a high degree of order [66]. Dendrimers can have additional biocompatible substances added to their free ends to reduce their toxicity and immunogenicity. ...
Effective management of neurodegenerative disorders like schizophrenia often remains problematic owing to the challenging brain microenvironment coupled with drug delivery issues across blood-brain barrier (BBB). In view of this, the delivery of medications through nanoparticle-mediated delivery systems is gaining popularity thanks to their structural, physico-chemical and pharmacokinetic uniqueness, which in turn improves therapeutic effectiveness. Schizophrenia remains an unaddressed medical condition, having unprecedented incidences across the globe having restricted therapeutic options for treatment. Treatment approaches are complicated due to the complex nature of schizophrenia, which involves a variety of genetic, neurological, and environmental components. Conventional antipsychotic drugs mainly target dopaminergic pathways; however, their effectiveness varies, and they frequently have a wide range of adverse effects that make treatment difficult. As mentioned, BBB stands as the main obstacle for the sub-therapeutic concentrations of drugs delivered through routine dosage forms. The inherent challenges of the BBB make it difficult for larger molecules and many hydrophilic compounds to cross into the central nervous system. However, polymeric-lipidic nanomediated platforms are now being largely explored to solve the issue. In view of the higher lipophilic nature and transcellular delivery pathway across BBB, the presence of phospho/ sphingolipids in the formulation further adds an advantage in achieving desired brain concentration. The present review compiles recent advancements in the polymeric/lipidic nano-based modalities explored over past years for the management of schizophrenia. Additionally, important translational glitches associated with novel carriers have also been covered in a nutshell.
... As such, it is critical to divide all known dendrons and dendrimers into two distinctly separate categories, namely: Category (I): symmetrical branch cell and Category (II): asymmetrical branch-cell structures. This important issue of classifying all known dendrons and dendrimers according to their branch cell symmetry is discussed extensively elsewhere [49] and described briefly in Section 2.3. ...
... Meanwhile, Category (II): asymmetrical branch-cell dendrimers such as well as literally dozens of subsequent patent applications in that area. These issues and details have been reviewed extensively elsewhere [49]. ...
... The original "Starburst Polymer" concept [31] (Figure 22) was to envision dendrimers as macromolecular monomers, which could be covalently linked via their reactive surface groups into a wide range of higher-order macromolecular architectural motifs generally referred to as "Starburst Polymers". Currently, these poly(dendrimers) or oligo (dendrimers) [49] are referred to as megamers or megameric networks, respectively. Earlier, this concept was clearly demonstrated by the syntheses of core-shell tecto (dendrimers) [45,46], as well as random megamer-type structures, as described later [27]. ...
This perspective begins with an overview of the major impact that the dendron, dendrimer, and dendritic state (DDDS) discovery has made on traditional polymer science. The entire DDDS technology is underpinned by an unprecedented new polymerization strategy referred to as step-growth, amplification-controlled polymerization (SGACP). This new SGACP paradigm allows for routine polymerization of common monomers and organic materials into precise monodispersed, dendritic macromolecules (i.e., dendrons/dendrimers) with nanoscale sizes and structure-controlled features that match and rival discrete in vivo biopolymers such as proteins and nucleic acids (i.e., DNA, siRNA, mRNA, etc.). These dendritic architectures exhibit unprecedented new intrinsic properties widely recognized to define a new fourth major polymer architecture class, namely: Category (IV): dendrons, dendrimers, and random hyperbranched polymers after traditional categories: (I) linear, (II) cross-linked, and (III) simple-branched types. Historical confusion over the first examples of the structure confirmed and verified cascade, dendron, dendrimer, and arborol syntheses, while associated misuse of accepted dendritic terminology is also reviewed and clarified. The importance of classifying all dendrons and dendrimers based on branch cell symmetry and the significant role of critical nanoscale-design parameters (CNDPs) for optimizing dendritic products for pharma/nanomedicine applications with a focus on enhancing stealth, non-complement activation properties is presented. This is followed by an overview of the extraordinary growth observed for amphiphilic dendron/dendrimer syntheses and their self-assembly into dendritic supramolecular assemblies, as well as many unique applications demonstrated in pharma and nanomedicine, especially involving siRNA delivery and mRNA vaccine development. This perspective is concluded with optimistic expectations predicted for new dendron and dendrimer application roles in pharma, nanomedicine, and life sciences.
... Although these findings are meaningful, considering that the studies were conducted for the initial testing of delivery efficiency and covalent linkers might struggle to withstand the harsh conditions of the GI tract, pharmaceutical scientists might not find sufficient reasons to choose dendrimers over other nanocarriers based on these data alone. Notably, one of the most distinctive properties of dendrimers is their capability for covalent drug association within a unimolecular structure, unlike most competitive carriers that are multicomponent systems relying on non-covalent mechanisms (Svenson 2015;Tomalia et al. 2020). This capability, together with their surface versatility, enables the precise control of drug release, drug-ligand binding, biocompatibility, and biodistribution, potentially conferring substantial advantages in oral applications over nano-pharmaceutical carriers. ...
Dendrimers are highly branched tree-like nanostructures with inner cavities and surface versatility. Notably, multiple studies point to their potential in oral drug delivery, yet not much attention has been given compared to other nanocarriers.
This review provides an overview of dendrimer applications for oral drug delivery, highlighting important findings from previous and up-to-date research. We also discuss the essential aspects for understanding and further designing dendrimer-based formulations, including their unique properties, proposed mechanisms, surface engineering, biocompatibility, and biodistribution, all specifically in the context of oral applications. Our goal is to offer readers new insights into this topic and facilitate further exploration of these promising applications.
Dendrimers have demonstrated high potential for oral drug delivery. However, to maximize their utility in this field, they should clearly outperform other competitive nanocarriers in effectiveness and industrial viability. The unique properties of dendrimers, successfully utilized in various biomedical applications, need to be fully leveraged in oral drug delivery, with an additional focus on targeting indications relevant to oral use. We anticipate that future studies will present a strong opportunity to capitalize on the distinctive advantages of dendrimers in oral drug delivery applications.
... The defined area formed between the dendrons is protected by a surface decorated with a multivalent end group. This empty area is used to encapsulate various bioactive materials and bio-imaging agents (Klimova et al., 2018;Tomalia et al., 2020). The loading efficiency of dendrimers would increase with every generation level. ...
... The loading efficiency of dendrimers would increase with every generation level. For example, cationic amino groups on the surface of higher generation cationic dendrimers would contribute to better DNA binding and cellular uptake by transforming the complex into nanoscale polyplexes (Noriega-Luna et al., 2014;Tomalia et al., 2020). Therefore, the three main domains of the dendrimer architecture can be used for drug delivery, molecular sensors, genetic materials, enzymes, and bioimaging applications ( Figure 2). ...
A brain tumor is an uncontrolled cell proliferation, a mass of tissue composed of cells that grow and divide abnormally and appear to be uncontrollable by the processes that normally control normal cells. Approximately 25,690 primary malignant brain tumors are discovered each year, 70% of which originate in glial cells. It has been observed that the blood-brain barrier (BBB) limits the distribution of drugs into the tumour environment, which complicates the oncological therapy of malignant brain tumours. Numerous studies have found that nanocarriers have demonstrated significant therapeutic efficacy in brain diseases. This review, based on a non-systematic search of the existing literature, provides an update on the existing knowledge of the types of dendrimers, synthesis methods, and mechanisms of action in relation to brain tumours. It also discusses the use of dendrimers in the diagnosis and treatment of brain tumours and the future possibilities of dendrimers. Dendrimers are of particular interest in the diagnosis and treatment of brain tumours because they can transport biochemical agents across the BBB to the tumour and into the brain after systemic administration. Dendrimers are being used to develop novel therapeutics such as prolonged release of drugs, immunotherapy, and antineoplastic effects. The use of PAMAM, PPI, PLL and surface engineered dendrimers has proven revolutionary in the effective diagnosis and treatment of brain tumours. Ikbal AM (2023), Dendrimer: An update on recent developments and future opportunities for the brain tumors diagnosis and treatment.
... The internal space and terminal functional groups of dendrimers facilitate the encapsulation and coupling of drugs or other therapeutic molecules. In addition to their effectiveness as drug carriers, dendrimers are also single-molecule nanoparticles and are smaller than other self-assembled organic nanoparticles (e.g., liposomes and micelles) [34]. Notably, PEGylated dendrimers can also prolong blood circulation [35,36], and their small size (8-20 nm in diameter) facilitates tissue penetration. ...
... The internal space and terminal functional groups of dendrimers facilitate the encapsulation and coupling of drugs or other therapeutic molecules. In addition to their effectiveness as drug carriers, dendrimers are also single-molecule nanoparticles and are smaller than other selfassembled organic nanoparticles (e.g., liposomes and micelles) [34]. Notably, PEGylated dendrimers can also prolong blood circulation [35,36], and their small size (8-20 nm in diameter) facilitates tissue penetration. ...
Targeted drug delivery is a precise and effective strategy in oncotherapy that can accurately deliver drugs to tumor cells or tissues to enhance their therapeutic effect and, meanwhile, weaken their undesirable side effects on normal cells or tissues. In this research field, a large number of researchers have achieved significant breakthroughs and advances in oncotherapy. Typically, nanocarriers as a promising drug delivery strategy can effectively deliver drugs to the tumor site through enhanced permeability and retention (EPR) effect-mediated passive targeting and various types of receptor-mediated active targeting, respectively. Herein, we review recent targeted drug delivery strategies and technologies for enhancing oncotherapy. In addition, we also review two mainstream drug delivery strategies, passive and active targeting, based on various nanocarriers for enhancing tumor therapy. Meanwhile, a comparison and combination of passive and active targeting are also carried out. Furthermore, we discuss the associated challenges of passive and active targeted drug delivery strategies and the prospects for further study.
... Docking analysis is widely used to predict interactions and the resulting energy [6]. Molecular dynamics can study the effect of the presence of an explicit solvent in the system, then it is applied to explore the conformation of protein receptors to improve the drug design process [7]. ...
Cervical cancer is the fourth most common female cancer worldwide and results in over 300000 deaths globally. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. The purpose of this study is to find out Monascus sp. as cervical anticancer using molecular docking and dynamics methods. The results of docked with AutodockTools were visualized with Pymol, analyzed the effectiveness using the Ramachandran plot. The docking results show that there are 2 pigments that have lower G than raloxifen in estrogen receptor beta with the lowest G indicated by the pigment Monascin and Ankaflavin, which is -6.94 kcal/mol with Ki value of 39.49 nM and -6.22 kcal/mol with Ki value of 27.78 nM. The results of molecular dynamics, Ankaflavin and Monascin have good stability at estrogen receptor beta because the outlier area has a value 11.722% and 10.256%. And the amino acid residues in the most preferred area were 68.864% and 70.330%. In addition, Monascopyridine B and Monascuspiloin pigments showed good and stable results at the EGFR receptor because the outlier areas were 14.692% and 10.623%. And the amino acid residues in the most-favored region were 65.403% and 73.260%. Based on the results of this study, we predict that Ankaflavin, Monascin, Monascopyridine B and Monascuspiloin can be used as new cervical anticancer candidates after validated with in vitro and in vivo tests.
... In general, dendrimers are in the nanoparticle range; several parameters can affect nano-encapsulation performance, including generation, type of end groups, surface charge, core structure, pH and environmental factors [75]. Symmetry also plays a very important role in determining the encapsulation properties [76] since this parameter di- Various families of peptide dendrimers have also been developed in recent years [65][66][67]; these dendrimers are branched macromolecules consisting of a peptidyl core and/or peptide functional groups at the peripheries attached in a covalent manner [68]. They can be symmetrical or unsymmetrical and used as diagnostic reagents, anticancer and antiviral agents, vaccines and carriers of active principles and genes [65,69], thanks to their properties of self-assembly [67,70]. ...
... In general, dendrimers are in the nanoparticle range; several parameters can affect nanoencapsulation performance, including generation, type of end groups, surface charge, core structure, pH and environmental factors [75]. Symmetry also plays a very important role in determining the encapsulation properties [76] since this parameter directs the internal stacking modes, which differentiate key properties of dendrimers, such as densities, refractive indices and internal porosities. Thus, symmetrical dendrimers encapsulate more than unsymmetrical ones. ...
Dendrimers are increasingly being studied in the context of encapsulation. Many potential applications of dendrimers are based on their properties. They are used in drug delivery systems, cosmetics, food and chemistry. This review is first devoted to different synthesis approaches for dendrimers and to their ability to encapsulate active molecules. Their applications in different fields, as well as their cytotoxicity, are then detailed. To conclude this review, the main works on the interaction of dendrimers with the stratum corneum (SC) are also presented.
... Most dendrimers currently in use for biomedical applications are composed of organic branches and generally mimic biopolymers: poly(amidoamine) dendrimers (PAMAM), poly(propylene imine) dendrimers (PPI), and poly(L-lysine) dendrimers (PLL) etc. [29,[69][70][71][72][73][74][75][76][77][78][79]. ...
DNA and RNA vaccines (nucleic acid-based vaccines) are a promising platform for vaccine development. The first mRNA vaccines (Moderna and Pfizer/BioNTech) were approved in 2020, and a DNA vaccine (Zydus Cadila, India), in 2021. They display unique benefits in the current COVID-19 pandemic. Nucleic acid-based vaccines have a number of advantages, such as safety, efficacy, and low cost. They are potentially faster to develop, cheaper to produce, and easier to store and transport. A crucial step in the technology of DNA or RNA vaccines is choosing an efficient delivery method. Nucleic acid delivery using liposomes is the most popular approach today, but this method has certain disadvantages. Therefore, studies are actively underway to develop various alternative delivery methods, among which synthetic cationic polymers such as dendrimers are very attractive. Dendrimers are three-dimensional nanostructures with a high degree of molecular homogeneity, adjustable size, multivalence, high surface functionality, and high aqueous solubility. The biosafety of some dendrimers has been evaluated in several clinical trials presented in this review. Due to these important and attractive properties, dendrimers are already being used to deliver a number of drugs and are being explored as promising carriers for nucleic acid-based vaccines. This review summarizes the literature data on the development of dendrimer-based delivery systems for DNA and mRNA vaccines.
... The defined area formed between the dendrons is protected by a surface decorated with a multivalent end group. This empty area is used to encapsulate various bioactive materials and bio-imaging agents (Klimova et al., 2018;Tomalia et al., 2020). The loading efficiency of dendrimers would increase with every generation level. ...
... The loading efficiency of dendrimers would increase with every generation level. For example, cationic amino groups on the surface of higher generation cationic dendrimers would contribute to better DNA binding and cellular uptake by transforming the complex into nanoscale polyplexes (Noriega-Luna et al., 2014;Tomalia et al., 2020). Therefore, the three main domains of the dendrimer architecture can be used for drug delivery, molecular sensors, genetic materials, enzymes, and bioimaging applications ( Figure 2). ...
A brain tumor is an uncontrolled cell proliferation, a mass of tissue composed of cells that grow and divide abnormally and appear to be uncontrollable by the processes that normally control normal cells. Approximately 25,690 primary malignant brain tumors are discovered each year, 70% of which originate in glial cells. It has been observed that the blood-brain barrier (BBB) limits the distribution of drugs into the tumour environment, which complicates the oncological therapy of malignant brain tumours. Numerous studies have found that nanocarriers have demonstrated significant therapeutic efficacy in brain diseases. This review, based on a non-systematic search of the existing literature, provides an update on the existing knowledge of the types of dendrimers, synthesis methods, and mechanisms of action in relation to brain tumours. It also discusses the use of dendrimers in the diagnosis and treatment of brain tumours and the future possibilities of dendrimers. Dendrimers are of particular interest in the diagnosis and treatment of brain tumours because they can transport biochemical agents across the BBB to the tumour and into the brain after systemic administration. Dendrimers are being used to develop novel therapeutics such as prolonged release of drugs, immunotherapy, and antineoplastic effects. The use of PAMAM, PPI, PLL and surface engineered dendrimers has proven revolutionary in the effective diagnosis and treatment of brain tumours.
... Dendrimer design with amine periphery makes it more attractive drug delivery carrier as compare to traditional carrier vehicle. Also, PAMAM dendrimer structure contains internal chamber which provide cargo space for hydrophobic drug molecules for incorporation through following host-guest chemistry (11). Amphotericin B is a polyene macrodile antifungal antibiotic that was procured from streptomyces nodosus in 1959. ...
Dendrimers, a new class of synthesized polymeric macromolecules, facilitate with advance utility in various bio-pharmacy research such target drug delivery, reduce toxicity, enhance solubility and improve bioavailability of drug molecule. Dendrimer manifest the potentiality as cargo channel to cross the membrane permeability at significant rate. PAMAM Dendrimer with ethylene di amine core is one of the most inspected and researched polymeric substances. PAMAM Dendrimer has a much higher amino surface group and its unique structure make its ideal vehicle for delivery of non soluble drugs. Amphotericin B is a polyene antifungal agent with zweteroinic nature. It is amphoteric in nature, containing both carboxyl and amino group, with charged nature at neutral pH. These molecular characteristic suppress its solubility in water and salt solutions. This poorly soluble nature blocks its utility in extermination of systemic fungal and protozoan burden and infirmity. In this research article we designed a conjugates of PAMAM dendrimer with Amphotericin B through physical encapsulation to midget its solubility issues because it's already established that amine terminated PAMAM dendrimer have great potentiality to deliver the low aqueous drug with improved solubilties.
