Chapter 10 - Dendrimers as Effective Carriers for the Treatment of Brain Tumor
Abstract
The tumor microenvironment impedes delivery of conventional chemotherapeutic agents at effective concentrations to tumor cells; hence the treatment lacks specificity and produces serious systemic toxicity. Thus, the struggle to develop an effective treatment against tumors is a primary role of researchers in improving the resulting morbidity and mortality caused by this fatal disease. Although the prevalence of brain tumors is low, they are considered to be the most lethal form of cancer. Delivery of chemotherapeutic agents across the tight junctions of the blood–brain barrier in the treatment of brain tumor is a great challenge, along with its targeting abilities and effectiveness. The branched molecular structure of PAMAM, PPL, and PPI dendrimers with or without targeting ligands has created great potential for nanotechnology to facilitate the transportation of chemotherapeutic agents across the BBB for the effective treatment of brain tumors.
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Future prospect of nano-based drug delivery approaches against pancreatic cancer and expected pitfalls of the technology
2023, Recent Advances in Nanocarriers for Pancreatic Cancer TherapySeveral scientific breakthroughs have undergone radical change as a result of the development of nanotechnology, but the introduction of nanomedicine stands out. Research has focused particularly on nano-drug administration for the treatment of cancer. Phytochemicals, or naturally occurring plant molecules, have been widely studied for their anticancer qualities. Due to its effectiveness in diagnosing and treating different malignancies, nanotechnology has recently attracted more interest. Nanocarriers have been used to get beyond the drawbacks of traditional anticancer drug delivery methods, such as their nonspecificity, adverse side effects, burst release, and harm to healthy cells, and improved by nanocarriers. Numerous nanocarriers were developed, but still, only a little has gotten clinical clearance for the transfer of anticancer drugs to the precise areas in which they will exert their desired effects. In the following chapter, conventional therapy for pancreatic cancer, the prospects of nanotechnology in pancreatic cancer treatment, the varied types of the drug delivery system, and challenges of nano-based drug delivery systems for pancreatic cancer therapy applications are discussed, which promises in terms of possible clinical translation.
Dendrimer–drug conjugates
2023, Polymer-Drug Conjugates: Linker Chemistry, Protocols and ApplicationsDendrimers have been emerged as a potential carrier for therapeutic agents due to the unique properties they possess, i.e., well-defined structure, monodispersity, and pliability for surface functionalization with ligands or therapeutic molecule. Dendrimers have been explored as scaffold for delivery of therapeutic agents. The presence of functional surface groups over periphery of dendrimers has been employed for conjugating the therapeutic entities through covalent bonding to improve drug release kinetics via stimuli-responsive, controlled, and targeted release of attached therapeutic moieties. The stimuli-responsive functionality allows the release of drug in response to the specific trigger (acid, redox potentials, or enzyme) at the targeted site. For the development of dendrimer–drug conjugates (DDCs), linker chemistry plays an important role in determining the optimal drug delivery at the targeted sites by conserving efficacy of therapeutic agent and influencing desired drug release pattern. DDCs have emerged as a promising delivery system with improved drug stability during systemic circulation, better pharmacokinetic profile, and targeted drug delivery. The DDCs have received a considerable attention for the delivery of various therapeutic agents including anticancer, antiinflammatory, and antimicrobial drugs. This chapter discusses the functionalization of dendrimers with drug either directly or via different linkers and highlights the significance of chemical nature of bonds for the controlled release of the free drug at the targeted site.
Dendrimers: an effective drug delivery and therapeutic approach
2023, Design and Applications of Theranostic NanomedicinesThe novel hyperbranched, three-dimensional tree-like globular dendritic structures are gaining popularity in the pharmaceutical field because of their attractive characteristics. The possibility of controlling narrow polydispersity index of the fabricated nanostructures possess homogeneous distribution of the particles with large numbers of surface groups for appropriate modification to target specifically to the diseased site. Incorporation of drugs to the void space or surface attachment has been applied through different routes of administration to target different topical diseases, carcinomas, and ailments in the central nervous system. Potential of this tree-like structure has also been progressed for theranostic use for diagnosis and treatment of cancer. Thus, this chapter has highlighted the usefulness of this dendritic structure and its application in the treatment of various diseases.
Futuristic aspect of nanocarriers on targeted delivery for dementia
2023, Nanomedicine-Based Approaches for the Treatment of DementiaAlzheimer’s disease (AD) is one of the most common neurodegenerative diseases. Analysis conducted over the past 20 years has shown that macromolecules accumulating in the brain known as Amyloid-β (Aβ) are fundamentally responsible for the chronic effects of the disease. Amyloid-β builds up in the brain, forming plaques, and clumps that block neuronal signaling and break down the connections between neurons. Many researchers have been looking at the involvement of tau, a protein that causes the production of “neurofibrillary tangles” in the brain, which is another signal of neuronal death. Proteolytic therapies for AD are one of the novel strategies where the proteolysis targeting chimera (PROTAC) is selectively initiating protein degradation within the cell. In this novel approach, these techniques are small-molecule PROTACs peptide, TH006, and Neprilysin-2 (NEP-2). The traditional drug delivery technologies confront difficulties in targeting specific parts of the brain. For drug discovery and development in order to make medications more effective in the brain and to have a specific action. The first line of defense for the brain is the blood–brain barrier, which is followed by the blood-cerebrospinal fluid barrier. These membranes are more than just barriers; they also serve as selectively permeable membranes, allowing particular molecules to invade the brain. These mechanisms all operate as impediments to effective drug delivery in the brain. As a result, improved strategies for facilitating the administration of such medications in the brain must be developed. Nanotechnology is now playing an important role in research, with a large number of nanoparticles intended to deliver drugs to specific target areas. Liposomes, dendrimers, microneedles, polymeric nanoparticles, and other nanoparticles are examples. Antibody-coated nanoparticles are a novel strategy to treating AD in the nanosystem.
Dendrimer-based delivery of macromolecules for the treatment of brain tumor
2022, Biomaterials AdvancesCitation Excerpt :Besides, the rapid systemic clearance of dendritic macromolecules also posed another challenge [118]. Smaller-sized G2 to G4 dendrimers could rapidly and easily be removed from the body through renal filtration [36]. At the same time, larger dendrimers will be removed by the RES.
Brain tumor represents the most lethal form of cancer with the highest mortality and morbidity rates irrespective of age and sex. Advancements in macromolecule-based therapy (such as nucleic acids and peptides) have shown promising roles in the treatment of brain tumor where the phenomenon of severe toxicities due to the conventional chemotherapeutic agents can be circumvented. Despite its preclinical progress, successful targeting of these macromolecules across the blood-brain barrier without altering their physical and chemical characteristics is of great challenge. With the advent of nanotechnology, nowadays targeted delivery of therapeutics is being explored extensively and these macromolecules, including peptides and nucleic acids, have shown initial success in the treatment, where dendrimer has shown its potential for optimal delivery. Dendrimers are being favored as a mode of drug delivery due to their nano-spherical size and structure, high solubilization potential, multivalent surface, and high loading capacity, where biomolecule resembling characteristics of dendritic 3D structures has shown effective delivery of various therapeutic agents to the brain. Armed with targeting ligands to these dendrimers further expedite the transportation of these multifunctional shuttles specifically to the glioblastoma cells. Thus, a focus has been made in this review on therapeutic applications of dendrimer platforms in brain tumor treatment. The future development of dendrimers as a potential platform for nucleic acid and peptide delivery and its promising clinical application could provide effective and target-specific treatment against brain tumors.
Nanocarrier mediated drug delivery as an impeccable therapeutic approach against Alzheimer's disease
2022, Journal of Controlled ReleaseFor the past several years, dementia, is one of the predominantly observed groups of symptoms in a geriatric population. Alzheimer’s disease (AD) is a progressive memory related neurodegenerative disease, for which the current Food and drug administration approved therapeutics are only meant for a symptomatic management rather than targeting the root cause of AD. These therapeutics belong to two classes, Acetylcholine Esterase inhibitors and N-methyl D-aspartate antagonist. Furthermore, to facilitate neuroprotective action in AD, the drugs are majorly expected to reach the specific target area in the brain for the desired efficacy. Thus, there is a huge requirement for drug discovery and development for facilitating the entry of drugs more in brain to exert a specific action. The very first line of defense and the major limitation for the entry of drugs into the brain is the Blood Brain Barrier, followed by Blood-Cerebrospinal Fluid Barrier. More than a barrier, these mainly act as selectively permeable membranes, which allows entry of specific molecules into the brain. Furthermore, specific enzymes result in the degradation of xenobiotics. All these mechanisms pose as hurdles in the way of effective drug delivery in the brain. Thus, novel techniques need to be harbored for the facilitation of the delivery of such drugs into the brain. Nanocarriers are advantageous for facilitating the specific targeted drug treatment in AD. As nanomedicines are one of the novels and most useful approaches for AD, thus the present review mainly focuses on understanding the advanced use of nanocarriers for targeted drug delivery in the management of AD.
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These authors contributed equally to this work.