Polymeric micelles for acyclovir drug delivery.
Ontology highlight
ABSTRACT:
SUBMITTER: Sawdon AJ
PROVIDER: S-EPMC4201986 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Publications
Polymeric micelles for acyclovir drug delivery.
Sawdon Alicia J AJ Peng Ching-An CA
Colloids and surfaces. B, Biointerfaces 20140820
Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PC ...[more]
Similar Datasets
Project description:To prepare mixed polymeric micelles that can carry two different drugs, doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for combination cancer chemotherapy.The pH-sensitive micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers to which either DOX or GDM-OH is conjugated through acid-labile hydrazone bond (individual micelles). Mixed micelles were formed not only by simply mixing two different individual micelles in aqueous solutions (aqueous mixed micelles) but also by evaporating organic solvents from the organic/aqueous mixed solvents in which two block copolymers possessing different drugs were dissolved homogeneously (organic mixed micelles). Particle size measurements, pH-dependent drug release tests, cytotoxicity assays and western blot analysis were subsequently conducted.Individual and aqueous/organic mixed micelles showed clinically relevant particle size (<100 nm) and pH-dependent drug release patterns. Mixed polymer micelles suppress cancer cell growth effectively in a drug concentration, mixing method and schedule-dependent way.Combination chemotherapy using polymeric micelles seems to minimize a schedule-dependent change in combination drug efficacy in comparison to drug combination using DMSO formulations.
| S-EPMC5568702 | biostudies-other
Project description:Polymeric micelles (PMs) have been widely investigated as nanocarriers for drug delivery and cancer treatments due to their excellent physicochemical properties, drug loading and release capacities, facile preparation methods, biocompatibility, and tumor targetability. They can be easily engineered with various functional moieties to further improve their performance in terms of bioavailability, circulation time, tumor specificity, and anticancer activity. The stimuli-sensitive PMs capable of responding to various extra- and intracellular biological stimuli (eg, acidic pH, altered redox potential, and upregulated enzyme), as well as external artificial stimuli (eg, magnetic field, light, temperature, and ultrasound), are considered as "smart" nanocarriers for delivery of anticancer drugs and/or imaging agents for various therapeutic and diagnostic applications. In this article, the recent advances in the development of stimuli-responsive PMs for drug delivery, imaging, and cancer therapy are reviewed. The article covers the generalities of stimuli-responsive PMs with a focus on their major delivery strategies and newly emerging technologies/nanomaterials, discusses their drawbacks and limitations, and provides their future perspectives.
| S-EPMC5965378 | biostudies-literature
Project description:Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance. We design three ionizable oligo-mers (IOs) that, with PLA-PEG, form Ionizable Polymeric Micelles (IPMs), a potential siRNA delivery system, which can achieve lysosomal escape. FAPi-modified IPMs (FAPi-IPMs) show higher targeting of activated hepatic stellate cells (HSCs) compared to hepatocytes, silencing both HSP47 and HMGB1, reducing collagen secretion and liv-er inflammation, effectively treating fibrosis. Moreover, IPMs and FAPi-IPMs mitigate accelerated blood clearance and produce fewer PEG antibodies than LNPs. Unlike LNPs, which adsorb apolipoprotein E (ApoE), IPMs and FAPi-IPMs show minimal apolipoprotein adsorption, differentiating their targeting effects from LNPs. In conclu-sion, IPMs represent an alternative nucleic acid delivery system with superior targeting and reduced immune clearance.
2024-11-21 | PXD057444 | Pride
Project description:Low tumor specificity and multidrug resistance (MDR) remain challenging for many anticancer drugs. In this study, the micelles assembled by a matrix metalloproteinase 2 (MMP2)-sensitive self-assembling efflux inhibitor (PEG2k-pp-PE) were developed and evaluated in various cancer models. In vitro, the PEG2k-pp-PE micelles enhanced the cellular uptake and tissue penetration and sensitized the cancers to drug treatments in MDR cancer cells and their three-dimensional multicellular spheroids. Their efflux inhibitory capability was comparable to those of the well-known small-molecule P-glycoprotein (P-gp) inhibitor and polymeric P-gp inhibitor. In vivo, the PEG2k-pp-PE micelles could specifically and effectively deliver the loaded cargoes to the tumor, as evidenced by the enhanced drug accumulation and prolonged drug retention in the tumor tissue, resulting in the improved anticancer activity. Our results suggest that the PEG2k-pp-PE micelles may have great potential to be a simple but multifunctional nanocarrier for concurrent tumor-targeted drug delivery and sensitization of resistant cancers.
| S-EPMC6599579 | biostudies-literature
Project description:It is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure property and self-assembly ability of pH-responsive amphiphilic block copolymer poly(methyl methacrylate-co-methacrylic acid)-b-poly(aminoethyl methacrylate) (poly(MMA-co-MAA)-b-PAEMA). The effects of different block ratios (hydrophilic PAEMA segment and pH-sensitive PMAA segment) in copolymer on self-assembly and drug loading capacity including drug distribution were extensively investigated. The increase of hydrophilic PAEMA facilitated the formation of a typical core-shell structure as well as a hydrophobic PMAA segment. Furthermore, the optimal drug-carrier ratio was confirmed by an analysis of the drug distribution during the self-assembly process of block copolymer and model drug Ibuprofen (IBU). In addition, the drug distribution and nanostructure of IBU-loaded polymeric micelles (PMs) self-assembled from precise block copolymer (PMMA-b-PMAA-b-PAEMA) and block copolymer (poly(MMA-co-MAA)-b-PAEMA) with random pH-responsive/hydrophobic structure were evaluated, showing that almost all drug molecules were encapsulated into a core for a random copolymer compared to the analogue. The nanostructures of IBU-loaded PMs at different pH values were evaluated. The results displayed that the nanostructure was stable at pH < pKa and anomalous at pH > pKa which indicated drug release, suggesting that the PMs could be used in oral drug delivery. These findings proved that the amphiphilic block copolymer P(MMA30-co-MAA33)-b-PAEMA38 with random structure and pH-sensitivity might be a potential drug carrier. Moreover, DPD simulation shows potential to study the structure property of PMs self-assembled from amphiphilic block copolymer.
| S-EPMC6956019 | biostudies-literature
Project description:To synthesize an effective and versatile nano-platform serving as a promising carrier for controlled drug delivery, visible-light-induced diselenide-crosslinked polyurethane micelles were designed and prepared for ROS-triggered on-demand doxorubicin (DOX) release. A rationally designed amphiphilic block copolymer, poly(ethylene glycol)-b-poly(diselenolane diol-co-isophorone diisocyanate)-b-poly(ethylene glycol) (PEG-b-PUSe-b-PEG), which incorporates dangling diselenolane groups within the hydrophobic PU segments, was initially synthesized through the polycondensation reaction. In aqueous media, this type of amphiphilic block copolymer can self-assemble into micellar aggregates and encapsulate DOX within the micellar core, forming DOX-loaded micelles that are subsequently in situ core-crosslinked by diselenides via a visible-light-triggered metathesis reaction of Se-Se bonds. Compared with the non-crosslinked micelles (NCLMs), the as-prepared diselenide-crosslinked micelles (CLMs) exhibited a smaller particle size and improved colloidal stability. In vitro release studies have demonstrated suppressed drug release behavior for CLMs in physiological conditions, as compared to the NCLMs, whereas a burst release of DOX occurred upon exposure to an oxidation environment. Moreover, MTT assay results have revealed that the crosslinked polyurethane micelles displayed no significant cytotoxicity towards HeLa cells. Cellular uptake analyses have suggested the effective internalization of DOX-loaded crosslinked micelles and DOX release within cancer cells. These findings suggest that this kind of ROS-triggered reversibly crosslinked polyurethane micelles hold significant potential as a ROS-responsive drug delivery system.
| S-EPMC11357037 | biostudies-literature
Project description:RNA interference (RNAi) drugs have significant therapeutic potential, but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide-co-N-(2-(pyridin-2-yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions and a second ampholytic block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization with an overall molecular weight of 22 000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL, respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90% mRNA knockdown and 65% protein knockdown at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates demonstrate the potential utility of this carrier design for delivering therapeutic siRNA drugs.
| S-EPMC3625707 | biostudies-literature
Project description:Oxidation-sensitive drug delivery systems (DDSs) have attracted attention due to the potential to improve efficacy and safety of chemotherapeutics. These systems are designed to release the payload in response to oxidative stress conditions, which are associated with many types of cancer. Despite extensive research on the development of oxidation-sensitive DDS, the lack of selectivity toward cancer cells over healthy cells remains a challenge. Here, we report the design and characterization of polymeric micelles containing thioether groups with varying oxidation sensitivities within the micellar core, which become hydrophilic upon thioether oxidation, leading to destabilization of the micellar structure. We first used the thioether model compounds, 3-methylthiopropylamide (TPAM), thiomorpholine amide (TMAM), and 4-(methylthio)benzylamide (TPhAM) to investigate the effect of the chemical structures of the thioethers on the oxidation by hydrogen peroxide (H2O2). TPAM shows the fastest oxidation, followed by TMAM and TPhAM, showing that the oxidation reaction of thioethers can be modulated by changing the substituent groups bound to the sulfur atom. We next prepared micelles containing these different thioether groups within the core (TP, TM, and TPh micelles). The micelles containing the thioether groups with a higher oxidation sensitivity were destabilized by H2O2 at a lower concentration. Micelle destabilization was also tested in human liver cancer (HepG2) cells and human umbilical vein endothelial cells (HUVECs). The TP micelles having the highest oxidation sensitivity were destabilized in both HepG2 cells and HUVECs, while the TPh micelles, which showed the lowest reactivity toward H2O2, were stable in these cell lines. The TM micelles possessing a moderate oxidation sensitivity were destabilized in HepG2 cells but were stable in HUVECs. Furthermore, the micelles were loaded with doxorubicin (Dox) to evaluate their potential in drug delivery applications. Among the micelles, the TM micelles loaded with Dox showed the enhanced relative toxicity in HepG2 cells over HUVECs. Therefore, our approach to fine-tune the oxidation sensitivity of the micelles has potential for improving therapeutic efficacy and safety of drugs in cancer treatment.
| S-EPMC10232214 | biostudies-literature
Project description:Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies.
| S-EPMC5319397 | biostudies-literature
Project description:Stimuli-responsive polymeric micelles (PMs) have shown great potential in drug delivery and controlled release in cancer chemotherapy. Herein, inspired by the features of the tumor microenvironment, we developed dual pH/redox-responsive mixed PMs which are self-assembled from two kinds of amphiphilic diblock copolymers (poly(ethylene glycol) methyl ether-b-poly(?-amino esters) (mPEG-b-PAE) and poly(ethylene glycol) methyl ether-grafted disulfide-poly(?-amino esters) (PAE-ss-mPEG)) for anticancer drug delivery and controlled release. The co-micellization of two copolymers is evaluated by measurement of critical micelle concentration (CMC) values at different ratios of the two copolymers. The pH/redox-responsiveness of PMs is thoroughly investigated by measurement of base dissociation constant (pKb) value, particle size, and zeta-potential in different conditions. The PMs can encapsulate doxorubicin (DOX) efficiently, with high drug-loading efficacy. The DOX was released due to the swelling and disassembly of nanoparticles triggered by low pH and high glutathione (GSH) concentrations in tumor cells. The in vitro results demonstrated that drug release rate and cumulative release are obviously dependent on pH values and reducing agents. Furthermore, the cytotoxicity test showed that the mixed PMs have negligible toxicity, whereas the DOX-loaded mixed PMs exhibit high cytotoxicity for HepG2 cells. Therefore, the results demonstrate that the dual pH/redox-responsive PMs self-assembled from PAE-based diblock copolymers could be potential anticancer drug delivery carriers with pH/redox-triggered drug release, and the fabrication of stimuli-responsive mixed PMs could be an efficient strategy for preparation of intelligent drug delivery platform for disease therapy.
| S-EPMC6523239 | biostudies-literature