Dendrimers as Modifiers of Inorganic Nanoparticles for Therapeutic Delivery in Cancer (original) (raw)

RECENT PROGRESS OF DENDRIMERS IN DRUG DELIVERY FOR CANCER THERAPY Review Article

International Journal of Applied Pharmaceutics, 2018

With the recent advances of nanotechnology, dendrimers are emerging as a highly attractive class of drug delivery vectors for cancer therapy. Dendrimers are multifunctional smart Nanocarriers to deliver one or more therapeutic agent safely and selectively to cancer cells. The high level of control over the synthesis of dendritic architecture makes dendrimers a nearly perfect (spherical) nanocarrier for site-specific drug delivery. The presence of functional groups in the dendrimers exterior also permits the addition of other moieties that can actively target certain diseases which are now widely used as tumor targeting strategies. Drug encapsulation, solubilization and passive targeting also equally contribute to the therapeutic use of dendrimers. Dendrimers are ideal carrier vehicles on cytotoxicity, blood plasma retention time, biodistribution and tumor uptake. In this review we highlight the advantages of dendrimers over conventional chemotherapy, toxicity and its management, following anticancer drugs delivered by using dendrimers and recent advances in drug delivery by various types of dendrimers as well as its diagnostic applications.

Fabrication and design of dendrimers for cancer chemotherapy

Bio-Research, 2019

Since the discovery of dendrimers in 1978, it has received serious attention as a drug carrier polymer most especially in cancer chemotherapeutics where precision and targeted delivery of drug to tumor cells is most desirable. Dendrimers are mostly synthetic, hyper-branched, tree-like globular, nano-sized polymers with excellent physicochemical properties that can be utilized in the formulation, design and delivery of drugs, vaccine and genes to specific receptors in the body. This review focused on the synthesis, types and applications of dendrimers in the delivery of cytotoxic drugs. The review shows that in the last decade, dendrimers have proved to be promising nanocarriers for various drugs including antiinflammatory, antimicrobial, and anticancer drugs. The application of dendrimers as scaffolds of prodrugs is particularly interesting. Dendrimers are relatively more stable compared with other nano drug carriers and are suitable in formulating drugs for different routes of administration. As more and newer dendrimers are introduced into the market, they will have increasing role in therapeutic delivery of drugs, vaccines and gene.

Tweaking dendrimers and dendritic nanoparticles for controlled nano-bio interactions: potential nanocarriers for improved cancer targeting

Journal of Drug Targeting, 2015

Nanoparticles have shown great promise in the treatment of cancer, with a demonstrated potential in targeted drug delivery. Among a myriad of nanocarriers that have been recently developed, dendrimers have attracted a great deal of scientific interests due to their unique chemical and structural properties that allow for precise engineering of their characteristics. Despite this, the clinical translation of dendrimers has been hindered due to their drawbacks, such as scale-up issues, rapid systemic elimination, inefficient tumor accumulation, and limited drug loading. In order to overcome these limitations, a series of reengineered dendrimers have been recently introduced using various approaches, including: i) modifications of structure and surfaces; ii) integration with linear polymers; and iii) hybridization with other types of nanocarriers. Chemical modifications and surface engineering have tailored dendrimers to improve their pharmacokinetics and tissue permeation. Copolymerization of dendritic polymers with linear polymers has resulted in various amphiphilic copolymers with self-assembly capabilities and improved drug loading efficiencies. Hybridization with other nanocarriers integrates advantageous characteristics of both systems, which includes prolonged plasma circulation times and enhanced tumor targeting. This review provides a comprehensive summary of the newly emerging drug delivery systems that involve reengineering of dendrimers in an effort to precisely control their nano-bio interactions, mitigating their inherent weaknesses.

Dendrimers: Nanopharmaceuticals for Drug Delivery

2010

Dendrimers are new class of polymeric materials. It is generally described as a macromolecule, which is characterized by its extensively branched 3D structure that provides a high degree of surface functionality and versatility. Dendrimers are highly branched, globular macromolecules with many arms emanating from a central core. The unique properties associated with these dendrimers such as uniform size, high degree of branching, water solubility, multivalency, well-defined molecular weight and available internal cavities make them attractive for biological and drug-delivery applications. Present review will have main focus on advantages, different synthesis strategies of dendrimers, types of dendrimers and recent studies on important applications of dendrimers.

Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

Journal of Pharmacy and Bioallied Sciences, 2014

S everal therapeutic agents suffer from various limitations like low aqueous solubility and short half-life. Therefore it is necessary to design a delivery system, which can deliver a drug efficiently. Conventional drug delivery systems are useful to some extent in overcoming these issues, but they have failed to prove their effectiveness in delivering many drugs. Nanoparticle assisted drug delivery provides a platform to modify the basic properties of drug molecules viz. solubility, half-life, biocompatibility and its release characteristics. Several nanoparticle based therapeutic products have been launched in the market while some are under clinical and preclinical trials. [1] Liposomes and polymeric-drug conjugates hold the maximum share of it. For instance, Doxil ® (doxorubicin HCl liposome injection) [2] and Abraxane ® (paclitaxel protein-bound particles for injectable suspension) [3] are administered as first-line treatments in various cancer types. The stability and toxicity issues associated with these technologies has remained a matter of concern untilnow. [1] The traditional linear polymers viz. polyethylene glycol (PEG), polyglutamic acid, polysaccharide, poly (allylamine hydrochloride) and N-(2-hydroxypropyl) methylacrylamide have been reviewed as drug delivery vehicles and accepted for clinical use, [4] but these linear polymers have poorly defined chemical structures. In this scenario, many attempts have been made to alleviate the problems associated with them. Moreover, the considerable interest of scientists in delivering therapeutic, targeting and diagnostic agents together in a single system has led to the usage of the novel class of nanoparticles as multifunctional platforms. The introduction of highly branched, well-defined molecular architectural polymers, i.e. Dendrimers, firstly in 1978 by Vogtle has provided a novel and one of the efficient nanotechnology platforms for drug delivery. [5] Dendrimers are three-dimensional, immensely branched, well-organized nanoscopic macromolecules (typically 5000-500,000 g/mol), possess low polydispersity index and have displayed an essential role in the emerging field of nanomedicine.

Dendrimers: Nanosized Multifunctional Platform for Drug Delivery

Drug Delivery Letters, 2018

Background: Dendrimers are nano-sized drug delivery systems that present significant advantages, including ease of construction, large number of polymers available for their synthesis and amenability to affix various types of ligands for targeting to specific site. The nanosystem with unique functional architecture and macromolecular characteristics has garnered considerable interest amongst researchers and various research reports and patents inputs can be found in literature. Objective: Till date more than ten families of dendrimers have been reported for their wide applications in medicine including diagnostic/clinical, and also in industrial arenas. Unlike traditional polymers, many dendrimers have remarkable features like improved aqueous solubility, biocompatibility, polyvalency and precise molecular weight. These features make dendrimers an ideal vehicle for drug delivery and targeting applications. Conclusion: The current review is an attempt to define types of dendrimers and their applications in drug delivery and cosmetics. The write up also highlights future perspectives of the multifunctional nanosystem.

Dendrimers as versatile platform in drug delivery applications

European Journal of Pharmaceutics and Biopharmaceutics, 2009

About forty percent of newly developed drugs are rejected by the pharmaceutical industry and will never benefit a patient because of poor bioavailability due to low water solubility and/or cell membrane permeability. New delivery technologies could help to overcome this challenge. Nanostructures with uniform and well-defined particle size and shape are of eminent interest in biomedical applications because of their ability to cross cell membranes and to reduce the risk of premature clearance from the body. The high level of control over the dendritic architecture (size, branching density, surface functionality) makes dendrimers ideal carriers in these applications. Many commercial small molecule drugs with anticancer, anti-inflammatory, and antimicrobial activity have been successfully associated with dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI or DAB) and poly(etherhydroxylamine) (PEHAM) dendrimers, either via physical interactions or through chemical bonding ('prodrug approach'). Targeted delivery is possible via targeting ligands conjugated to the dendrimer surface or via the enhanced permeability and retention (EPR) effect. The biocompatibility of dendrimers follows patterns known from other small particles. Cationic surfaces show cytotoxicity; however, derivatization with fatty acid or PEG chains, reducing the overall charge density and minimizing contact between cell surfaces and dendrimers, can reduce toxic effects.

Surface modified dendrimers: Synthesis and characterization for cancer targeted drug delivery

Dendrimers represents a highly branched three-dimensional structure that provides a high degree of surface functionality and versatility. PAMAM dendrimers are used as well-defined nanocontainers to conjugate, complex or encapsulate therapeutic drugs or imaging moieties. Star-burst [PAMAM] dendrimers represent a superior carrier platform for drug delivery. The present study was aimed at synthesis of a surface modified dendrimer for cancer targeted drug delivery system. For this 4.0 G PAMAM dendrimer was conjugated with Gallic acid [GA] and characterized through UV, IR, 1H NMR and mass spectroscopy. Cytotoxicity study of dendrimer conjugate was carried out against MCF-7 cell line using MTT assay. The study revealed that the conjugate is active against MCF-7 cell line and might act synergistically with anti-cancer drug and gallic acid–dendrimer conjugate might be a promising nano-platform for cancer targeting and cancer diagnosis.

Dendrimer-based strategies for cancer therapy: Recent advances and future perspectives

Science China Materials, 2018

This review reports some recent advances on the use of dendrimer-based systems for cancer therapy. Dendrimers are emerging as promising carriers or stabilizers for drugs and nanoparticles (NPs) due to their highly branched 3dimensional globular shape, internal hydrophobic cavity and multiple peripheral functional groups. The fabricated nanoplatforms loaded with therapeutic agents such as drugs, siRNAs or NPs can be further modified to have targeting specificity, antifouling properties and good biocompatibility. In particular, recent advances in the surface modifications of dendrimers and the application of dendrimers as versatile platforms for different therapeutic treatments to cancer including chemotherapy, radiotherapy, photothermal therapy, photodynamic therapy, gene therapy, and combination therapy will be introduced in detail.