From Stealthy Polymersomes and Filomicelles to “Self” Peptide-Nanoparticles for Cancer Therapy (original) (raw)
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Functionalized Polymeric Nanoparticles: A Novel Targeted Approach for Oncology Care
International Journal of Applied Pharmaceutics
Popular cancer therapies face extreme disadvantages, including multimedicament tolerance and non-target impact. These issues will lead to poorer patient conformity and poor levels of survival. Successful medical therapies for cancer patients are desperately required. Nano-particulate structures with a pluronic base represent revolutionary platforms for anti-cancer agent provision. These structures provide great potential for the advancement of cancer therapy due to their pharmacological properties and sufficient physicochemical characteristics. This review aims to offer a more detailed description of the pluronic drug delivery mechani sms that are currently available and explains pluronic as a medicinal polymer. Hydrophobic payload formulations and updated, targeted distribution mechanisms are explained based on pluronic formulations. This analysis offers a rundown of the current situation art related to the theranostic application of polymer micelles targeting the microenvironment ...
Multifunctional Polymeric Nanosystems for Tumor-Targeted Delivery
Cancer is the second leading cause of morbidity and mortality in the United States, with occurrences portraying an upward trend for the future. In 2007, approximately 10 million cases of cancer will occur globally, with a total of around 1.5 million new cancer cases and over 560,000 deaths expected in the United States (U.S. National Institute of Health, 2006). Strikingly, remarkable advances in diagnosis and therapy of cancer have been made over the past few decades resulting from significant advances in fundamental cancer biology. What lacks in this case is clinical translation of these advances into effective therapies. A major hurdle in cancer diagnosis and therapy is the targeted and efficacious delivery of agents to the tumor site, while avoiding adverse damage resulting from systemic administration. While systemic drug delivery already hinges largely on physicochemical properties of the drug, such as size, diffusivity, and plasma protein binding affinity, tumors possess a dense, heterogeneous vasculature and an outward net convective flow that act as hurdles to efficient drug deposition at the target site (Jang et al., 2003). Nanocarriermediated delivery has emerged as a successful strategy to enhance delivery of therapeutics and imaging agents to tumors, thereby increasing the potential for diagnosis at an earlier stage or for therapeutic success (or both). Based on the initial observation by Maeda and Matsumura that tumors possess a fenestrated vasculature, with pores on average ranging between 200 and 800 nm, and a lack of lymphatic drainage, together termed the enhanced permeability and retention (EPR) effect, it was found that colloidal carriers in the nanometer size range could target tumors passively, by specific extravasation through these fenestrations, and are retained at the site for prolonged time because of lack of lymphatic drainage (Matsumura and Meada, 1986). This physiological advantage has been used successfully to enhance delivery of diagnostic and therapeutic agents, leading to the U.S. Food and Drug Administration (FDA) approval of nanoparticle formulations such as Feridex® for diagnostic applications and Doxil® and Abraxane® for cancer therapy (U.S. Food and Drug Administration, 2006).
International Journal of Pharmaceutics, 2019
The biological barriers in the body have been fabricated by nature to protect the body from foreign molecules. The successful delivery of drugs is limited and being challenged by these biological barriers including gastrointestinal tract, brain, skin, lungs, nose, mouth mucosa and immune system. In this review article, we envisage to understand the functionalities of these barriers and revealing various drug-loaded biodegradable polymeric nanoparticles to overcome these barriers and deliver the entrapped drugs to the cancer targeted site. Apart from it, tissue specific multifunctional ligands, linkers and transporters when employed imparts an effective active delivery strategy by receptor mediated transcutosis. Together, these strategies enable to deliver various drugs across the biological membranes for the treatment of solid tumors and malignant cancer.
Molecular Pharmaceutics, 2006
Carrier-mediated delivery of drugs into the cytosol is often limited by either release from the carrier or release from an internalizing endolysosome. Here, loading, delivery, and cytosolic uptake of drug mixtures from degradable polymersomes are shown to exploit both the thick membrane of these block copolymer vesicles and their aqueous lumen as well as pHtriggered release within endolysosomes. Our initial in vivo studies demonstrate growth arrest and shrinkage of rapidly growing tumors after a single intravenous injection of polymersomes composed of poly(ethylene glycol)-polyester. Vesicles are shown to break down into membranelytic micelles within hours at 37°C and low pH, although storage at 4°C allows retention of drug for over a month. It is then shown that cell entry of the polymersomes into endolysosomes is followed by copolymer-induced endolysosomal rupture with release of cytotoxic drugs. Above a critical poration concentration (C CPC ) that is easily achieved within endolysosomes and that scales with copolymer proportions and molecular weight, the copolymer micelles are seen to disrupt lipid membranes and thereby enhance drug activity. Neutral polymersomes and related macrosurfactant assemblies can thus create novel pathways within cells for controlled release and delivery. (1) Sonawane, N. D.; Szoka, F. C.; Verkman, A. S. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. J. Biol. Chem. 2003, 278, 44826-44831. (2) Lim, Y.-B.; Kim, S.-M.; Suh, H.; Park, J.-S. Biodegradable, endosome disruptive, and cationic network-type polymer as a highly efficient and nontoxic gene delivery carrier. Bioconjugate Chem. 2002, 13, 952-957. articles 340 MOLECULAR
to be a prior method against cancer, chemotherapeutics usually fail due to the poor water solubility, high toxicity, and low bioavailability. To solve these problems, nanotechnology-mediated drug delivery system (NDDS) has emerged. Nanoparticles (NPs), especially those that are made from biodegradable and biocompatible polymers, have been widely utilized as NDDS for cancer therapy. Using nanotechnology, it is possible to achieve improved delivery of poorly water-soluble drugs, targeted delivery of drugs in a cell-or tissue-specific manner, codelivery of two or more drugs for combination therapy, etc. Hence, with all these advantages, NPs can be an outstanding candidate for loading chemotherapeutics.
Monoclonal antibody-targeted polymeric nanoparticles for cancer therapy - future prospects
Journal of Chemical Technology & Biotechnology, 2014
Although combination therapy for cancer utilising monoclonal antibodies in conjunction with chemotherapeutic drugs has resulted in increases in five year survivals, there nevertheless remains significant morbidity and mortality associated with systemic delivery of cytotoxic drugs. The advent of living radical polymerisation has resulted in complex and elegant nanoparticle structures that can be engineered to passively target a drug payload for cancer treatment. This presents a therapeutic modality whereby biodistribution and consequently systemic toxicity can be reduced, while focussing drug delivery to the tumour site.
Perspective highlights on biodegradable polymeric nanosystems for targeted therapy of solid tumors
BioImpacts
Introduction: Polymeric nanoparticles (NPs) formulated using biodegradable polymers offer great potential for development of de novo drug delivery systems (DDSs) capable of delivering a wide range of bioactive agents. They can be engineered as advanced multifunctional nanosystems (NSs) for simultaneous imaging and therapy known as theranostics or diapeutics. Methods: A brief prospective is provided on biomedical importance and applications of biodegradable polymeric NSs through reviewing the recently published literature. Results: Biodegradable polymeric NPs present unique characteristics, including: nanoscaled structures, high encapsulation capacity, biocompatibility with non-thrombogenic and nonimmunogenic properties, and controlled-/sustained-release profile for lipophilic and hydrophilic drugs. Once administered in vivo, all classes of biodegradable polymers (i.e., synthetic, semi-synthetic, and natural polymers) are subjected to enzymatic degradation; and hence, transformation into byproducts that can be simply eliminated from the human body. Natural and semi-synthetic polymers have been shown to be highly stable, much safer, and offer a non-/lesstoxic means for specific delivery of cargo drugs in comparison with synthetic polymers. Despite being biocompatible and enzymatically-degradable, there are some drawbacks associated with these polymers such as batch to batch variation, high production cost, structural complexity, lower bioadhesive potential, uncontrolled rate of hydration, and possibility of microbial spoilage. These pitfalls have bolded the importance of synthetic counterparts despite their somewhat toxicity. Conclusion: Taken all, to minimize the inadvertent effects of these polymers and to engineer much safer NSs, it is necessary to devise biopolymers with desirable chemical and biochemical modification(s) and polyelectrolyte complex formation to improve their drug delivery capacity in vivo.
Multicomponent Polymeric Nanoparticles Enhancing Intracellular Drug Release in Cancer Cells
ACS Applied Materials & Interfaces, 2014
Three kinds of amphiphilic copolymer i.e. Poly(ε-caprolactone)-SS-Poly(ethylene glycol) (PCL-SS-PEG), Poly(ε-caprolactone)-Polyethylenimine (PCL-PEI) and Poly(ε-caprolactone)-Polyethylenimine-Folate (PCL-PEI-Fol) were synthesized and self-assembled into surface engineered hybrid nanoparticles (NPs). Morphological studies elucidated the stable, spherical and uniform sandwich structure of NPs. PCL-PEI and PCL-SS-PEG segments have introduced pH and reduction responsive characteristics in these NPs, while PCL-PEI-FA copolymers could provide specific targeting capability to cancer cells. The stimuli responsive capabilities of these NPs were carried out. Negative-to-positive charge reversible property, in response to the pH change, was investigated by Zeta potential and Nuclear Magnetic Resonance (NMR). The structure cleavage, due to redox gradient, was studied by Dynamic Light Scattering (DLS) and Transmission Electron Microscope (TEM). These NPs showed controlled degradation, better drug release, less toxicity and effective uptake in MCF-7 breast cancer cells. These multifunctional NPs showed promising potential in the treatment of cancer.