Hydrophobic Drug Carrier Research Articles

CEST effect of dimethyl sulfoxide at negative offset frequency.

Dimethyl sulfoxide (DMSO) has wide biomedical applications such as cryoprotectant and hydrophobic drug carrier. Here, we report for the first time that DMSO can generate a distinctive chemical exchange saturation transfer (CEST) signal at around -2ppm. Structural analogs of DMSO, including aprotic and protic solvents, also demonstrated CEST signals from -1.4 to -3.8ppm. When CEST detectable barbituric acid (BA) was dissolved in DMSO solution and was co-loaded to liposome, two obvious peaks at 5 and -2ppm were observed, indicating that DMSO and related solvent system can be monitored in a label-free manner via CEST, which can be further applied to imaging drug nanocarriers. With reference to previous studies, there could be molecular interactions or magnetization transfer pathways, such as the relayed nuclear Overhauser enhancement (rNOE), that lead to this detectable CEST contrast at negative offset frequencies of the Z-spectrum. Our findings suggest that small molecules of organic solvents could be involved in magnetization transfer processes with water and readily detected by CEST magnetic resonance imaging (MRI), providing a new avenue for detecting solvent-water and solvent-drug interactions.

Core-Tunable Dendritic Polymer: A Folate-Guided Theranostic Nanoplatform for Drug Delivery Applications.

Clinical application of anticancer drugs is mostly limited due to their hydrophobic nature, which often results in lower bioavailability and lesser retention in systemic circulation. Despite extensive research on the development of targeted drug delivery systems for cancer treatment, delivery of hydrophobic therapeutic drugs to tumor cells remains a major challenge in the field. To address these concerns, we have precisely engineered a new hyperbranched polymer for the targeted delivery of hydrophobic drugs by using a malonic acid-based A2B monomer and 1,6-hexanediol. The choice of monomer systems in our design allows for the formation of higher molecular weight polymers with hydrophobic cavities for the efficient encapsulation of therapeutic drugs that exhibit poor water solubility. Using several experimental techniques such as NMR, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform-infrared (FT-IR), and gel permeation chromatography (GPC), the synthesized polymer was characterized, which indicated its dendritic structure, thermal stability, and amorphous nature, making it suitable as a drug delivery system. Following characterizations, theranostic nanoplatforms were formulated using a one-pot solvent diffusion method to coencapsulate hydrophobic drugs, BQU57 and doxorubicin. To achieve targeted delivery of loaded therapeutic drugs in A549 cancer cells, the surface of the polymeric nanoparticle was conjugated with folic acid. The therapeutic efficacy of the delivery system was determined by various cell-based in vitro experiments, including cytotoxicity, cell internalizations, reactive oxygen species (ROS), apoptosis, migration, and comet assays. Overall, findings from this study indicate that the synthesized dendritic polymer is a promising carrier for hydrophobic anticancer drugs with higher biocompatibility, stability, and therapeutic efficacy for applications in cancer therapy.

Benzoylation of Iota Carrageenan: Development of a Stable, Conductive, and Hydrophobic Drug Carrier with Reduced Toxicity and Improved Gel‐Forming Ability

Benzoylation of Iota Carrageenan: Development of a Stable, Conductive, and Hydrophobic Drug Carrier with Reduced Toxicity and Improved Gel‐Forming Ability

Benzoylation of Iota Carrageenan: Development of a Stable, Conductive, and Hydrophobic Drug Carrier with Reduced Toxicity and Improved Gel‐Forming Ability

AbstractIota carrageenan is characterized as a hydrocolloid, with the limitations of hygroscopicity and hydrophilicity. Here, each of these factors is addressed to enhance the stability, and hydrophobicity through the protection of highly reactive primary alcohol and the formation of stable, improved hydrophobic, and conductive gel for the loading of lipophilic drugs. The functionalized polymer is evaluated through the microscopic and scanning electron microscopy (SEM) image of the compounds, which confirm the confined nature of the functionalized polymer. Moreover, the values changed from compound 1 (iota carrageenan) to compound 2 (benzoyl liked iota carrageenan) included Log P (partition coefficient) from −0.97 to 0.90, calculated partition coefficient (cLog P) from −2.50 to 0.12, and total polar surface area (TPSA) from 214.1 to 208.57, which strongly suggest the enhanced hydrophobic character of functionalized polymers. The enhancement is further concluded by the loading of the lipophilic drug inside the core of functionalized polymer‐based gel. The enhanced loading of the drug clearly shows the improved hydrophobicity (56–86%) of the gel core of the functionalized compounds. In summary, a polymer with enhanced stability, hydrophobicity, conductivity, and capacity to make a more stable gel, with enhanced drug‐loading capability of water‐insoluble drugs, will be the best way to resolve the low bioavailability issue of the water‐insoluble drug.

Synthesis and characterization of the redox-responsive amphiphilic fluorescent alginate derivatives as the multi-functional hydrophobic anticancer drug delivery system with visualization and sustained release

To develop the multi-functional hydrophobic anticancer drug carriers with visualization and sustained release, a novel amphiphilic alginate derivative (LSA-SS-DEAC) containing chromophobe groups was designed and synthesized by grafting hydrophobic fluorescent molecule, 7-(diethylamino-coumarin-3-carboxylic acid (DEAC-COOH) onto hydrophilic low molecular alginate backbone through cystamine by water-soluble carbodiimide chemical method. The molecular structure and self-assembly properties of the synthesized LSA-SS-DEAC were characterized. Furthermore, the encapsulation of anti-cancer drugs, doxorubicin hydrochloride (DOX) in LSA-SS-DEAC self-assembled micelles was realized by ultrasonic dialysis method. Subsequently, the in vitro drug release behavior and in vitro cytotoxicity of LSA-SS-DEAC micelles in simulated tumor microenvironment were also studied. The resultant LSA-SS-DEAC with the critical micelle concentration (CMC) of 0.26 mg/mL exhibited the ability to spontaneously form spherical micelles with the particle size of 250.2 ± 4.3 nm (PDI = 0.23) and zeta potential of −49.1 ± 0.4 mV, which presented good stability in pH 7.4 PBS and excellent fluorescence properties and redox responsiveness. The drug-loaded LSA-SS-DEAC micelles had the optimal EE value of about 42.2% when the DOX/LSA-SS-DEAC mass ratio was 3:10. Meanwhile, The drug-loaded LSA-SS-DEAC micelles exhibited sustained release in GSH-free environment, and the cumulative drug release rates were 40.3% and 46.6% in pH 7.4 and 5.0 PBS for 48 h, respectively. However, in the simulated tumor cell microenvironment (pH 5.0 PBS + 10 mM GSH), the disulfide bond between the core-shell was broken under the GSH trigger, and the LSA-SS-DEAC micelles collapsed, resulting in a cumulative drug release rate of about 64% at 12 h. In vitro cytotoxicity results showed that LSA-SS-DEAC had low cytotoxicity, and revealed obvious inhibitory effect on HeLa cells after DOX loading. Fluorescence imaging results indicated that LSA-SS-DEAC micelles could emit green light after ingested by cells, and their fluorescence properties were not affected after encapsulation of DOX. Accordingly, LSA-SS-DEAC micelles had the potential for drug localization tracking and rapid drug release at focal sites, which could be expected to be an ideal drug carriers for hydrophobic anticancer drug delivery.

Silk Nanofiber Carriers for Both Hydrophilic and Hydrophobic Drugs to Achieve Improved Combination Chemotherapy.

Combination chemotherapy is considered an effective strategy to inhibit tumor growth. Here, beta-sheet-rich silk nanofibers are co-loaded with hydrophilic doxorubicin (DOX) and hydrophobic paclitaxel (PTX) through a sequential physical blending-centrifugation-blending process. The ratio and amount of DOX and PTX on the nanofibers are regulated independently to optimize cooperative interaction. Both PTX and DOX are immobilized on the same nanofibers to avoid burst release problems. Besides the water-insoluble PTX, more than half of the DOX remained fixed on the nanofibers for more than 28 days, which facilitated the co-internalization of both DOX and PTX by tumor cells in vitro. Changing the ratio of co-loaded DOX and PTX achieved optimal combination therapy in vitro. The DOX-PTX co-loaded nanofibers are assembled into injectable hydrogels to facilitate in situ injection around tumor tissues in vivo. Long-term inhibition is achieved for tumors treated with DOX-PTX co-loaded hydrogels, superior to those treated with free DOX and PTX, and hydrogels loaded with only DOX or PTX. Considering the mild and controllable physical loading process and superior loading capacity for both hydrophilic and hydrophobic ingredients, these injectable silk nanofiber hydrogels are promising carriers to deliver multiple drug types simultaneously in situ, enhancing combination chemotherapies towards clinical applications.

Layered Double Hydroxides as an Intercalation System for Hydrophobic Molecules.

Layered double hydroxides (LDHs) have been extensively studied as drug delivery systems due to their favorable characteristics, including biocompatibility, high loading efficiency, and pH-responsive release. However, the current research predominantly focuses on LDHs as carriers for various anionic drugs, while there are only limited reports on LDHs as carriers for hydrophobic drugs. In this study, we successfully achieved the loading of a hydrophobic drug mimic, Nile red (NR), into LDHs using sodium dodecyl sulfate (SDS) as an intermediate storage medium. Furthermore, we optimized the experimental methods and varied the SDS/NR molar ratio to optimize this intercalation system. With an increase in the SDS/NR molar ratio from 2/1 to 32/1, the loading efficiency of LDH-SDS-NR for NR initially increased from 1.32% for LDH-SDS-NR_2/1 to 4.46% for LDH-SDS-NR_8/1. Then, the loading efficiency slightly decreased to 3.64% for LDH-SDS-NR_16.8/1, but then increased again to 6.31% for LDH-SDS-NR_32/1. We believe that the established method and the obtained results in this study broaden the application scope of LDHs as delivery systems for hydrophobic drugs and contribute to the further expansion of the application scope of LDHs.

Alginic acid-based pH and thermo responsive reversible switched polymeric micelle via RAFT polymerization

Amphiphilic copolymers derived from natural polymers have drawn significant interest as hydrophobic drug carriers owing to their hydrophobic core and hydrophilic exterior shell. In this context, a new amphiphilic copolymer, Alg-g-PNIPAAm, was synthesized by inserting thermoresponsive N-isopropylacrylamide (NIPAAm) on an alginate-modified macro-RAFT reagent (Alg-DSCPA) through the reversible addition fragmentation chain transfer (RAFT) technique. Alg-g-PNIPAAm has shown stimuli-responsive (pH and temperature) reversible micellization behavior, which permits controlled micelle formation as well as phase separation. Dipyridamole (DP), a model hydrophobic drug, has been encapsulated on micelles via hydrophobic interactions. The drug loading was found to be ∼37 %, while the encapsulation efficiency was found to be ∼75 %. The DP-loaded micelles revealed pH- and thermoresponsive release patterns with enhanced therapeutic efficacy. Additionally, the copolymer has been found to be noncytotoxic against HEK293T, HeLa and HCT116 cells lines, which enhanced its applicability in the field of drug delivery.

Controlled drug release from policaprolactone-piperine electrospun scaffold for bone tissue engineering

Polymeric drug scaffolds have been intensively studied in orthopedic surgery due to their capacity for the regimented and site-specific liberation of the therapeutic agent at the intended locus. In this context, electrospinning is a promising technique for producing scaffolds using biodegradable and biocompatible polymers. In the present study, scaffolds of Polycaprolactone (PCL) with Piperine (PIP) incorporated at different concentrations (1, 3, and 5 %) were obtained by electrospinning. The electrospun PCL, PCL/PIP 1 %, PCL/PIP 3 %, and PCL/PIP 5 % groups were analyzed by FTIR spectroscopy to identify the incorporated drug and through UV-VIS spectroscopy to evaluate its controlled release. In addition, the bone repair was verified by Raman spectroscopy using ᶹ1PO43- vibration data obtained by in vivo analysis. The morphology and diameter of the nanofibers were obtained by scanning electron microscopy (SEM). The PCL, PCL/PIP 1 %, PCL/PIP 3 %, PCL/PIP 5 % scaffolds had diameters of 0.0015 ± 0.002 μm, 1.08 ± 0.007 μm, 1.09 ± 0.02 μm, 0.59 ± 0.016 μm, respectively. Piperine release was pronounced after 15 days. Therefore, at 30 days, the PCL/PIP 1 % scaffold released 64 % ± 0.00062, while the PCL/PIP 3 % and PCL/PIP 5 % scaffolds released only 16.06 ± 0.00012 and 9.08 % ± 0.00031, respectively. This study provided evidence that PCL/Piperine can be used to significantly increase bone regeneration. Results from Raman spectroscopy and histological analysis demonstrated that the PCL/PIP 1 %, 3 %, and 5 % groups had better bone regeneration than the negative control group after 15 days and 30 days of treatment. The prolonged release of piperine promoted by PCL, a hydrophobic drug carrier, caused the neoformation of the bones to be restricted to the inner part of the bone defect, creating an immature bone with evident cellular differentiation.

Hyaluronic acid anchored paclitaxel nanoparticles to solubilize for drug delivery

Amphiphilic oxidation-responsive prodrug (HPPCD) was firstly designed and synthesized in this study for resolving the hydrophobic nature of first-line anticancer drug paclitaxel (PTX), which was composed of hydrophilic β-cyclodextrin units and hyaluronic acid (HA) units. According to the biocompatibility and binding affinity between the synthetic conjugates and PTX, nanoparticles were prepared self-assembly. The solubilization were measured to be ca. 8000-fold increase compared to free paclitaxel (PTX), indicating about 2 mg/mL of solubility. In addition, cytotoxicity and wound healing assays showed the anticancer ability of the nanoparticles. The cellular investigations exhibited the time-dependent internalization and HA-mediated endocytosis. Apoptosis and cell cycle assays were performed to prove the retardation and further apoptosis. Three-dimensional spheroids (3DS) were constructed to mimic the tumors in vivo and further verify the anticancer capacity. Collectively these findings present HPPCD can be the potential insight as the carrier for hydrophobic drugs and further improve the cancer therapy.

Synthesis of heparin-and-poloxamer P407-based nanogel carrying PTX for orientating in treatment of breast cancer

In this study, nanogels based on the conjugation of heparin and poloxamer P407 (HR-P407) with different grafting ratios were successfully synthesised. The structural properties of products were evaluated by Fourier-transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H-NMR). The morphology and size of nanoparticles were assessed by dynamic light scattering (DLS) method, which showed that particle size distribution was from 144 nm to 214 nm. The HR-P407 nanogel systems were biocompatible and non-toxic to healthy cells. While free PTX displayed rapid and potent cytotoxic effects, PTX released from HR-P407 (1:10)/PTX demonstrated a gradual and sustained cytotoxicity. This controlled release mechanism allowed prolonged drug exposure, reducing acute toxicity and enhancing cytotoxicity over time. The results suggest that the synthesised nanogels can be used as an effective hydrophobic anticancer drug carrier system.

Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs

Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs

Preparation and characterization of glyceryl dibehenate and glyceryl monostearate -based lyotropic liquid crystal nanoparticles as carriers for hydrophobic drugs

Preparation and characterization of glyceryl dibehenate and glyceryl monostearate -based lyotropic liquid crystal nanoparticles as carriers for hydrophobic drugs

The effects of biliverdin on pressure-induced unfolding of apomyoglobin: The specific role of Zn2+ ions

Apomyoglobin (apoMb), a model protein in biochemistry, exhibits a strong propensity to bind various ligands, which makes it a good candidate as a carrier of bioactive hydrophobic drugs. The stability of its hydrophobic pocket determines its potential as a carrier of bioactive compounds. High pressure (HP) is a potent tool for studying protein stability, revealing the specific role of hydrophobic cavities in unfolding. We probed the effects of biliverdin (BV) binding and its complex with Zn2+ ions on the structure and HP stability of apoMb. CD spectroscopy and SAXS measurements revealed that BV and BV-Zn2+ complexes make the apoMb structure more compact with higher α-helical content. We performed in situ HP measurements of apoMb intrinsic fluorescence to demonstrate the ability of BV to stabilise apoMb structure at HP conditions. Furthermore, the presence of Zn2+ within the apoMb-BV complex significantly enhances the BV stabilisation effect. In situ visible absorption study of BV chromophore confirmed the ability of Zn2+ to increase the stability of apoMb-BV complex under HP: the onset of complex dissociation is shifted by ∼100 MPa in presence of Zn2+. By combining HP-fluorescence and HP-visible absorption spectroscopy, our strategy highlights the crucial role of tetrapyrrole-metal complexes in stabilising apoMb hydrophobic pocket.

Maslinic acid solid lipid nanoparticles as hydrophobic anticancer drug carriers: Formulation, in vitro activity and in vivo biodistribution

Maslinic acid (MA) is a natural pentacyclic triterpenoid with inherent antitumor activity which has a very low solubility in water. MA solid lipid nanoparticles (SLNs) were prepared using Poloxamer 407 and Dicarboxylic acid-Poloxamer 407 as surfactants. Both MA SLNs are monodisperse, with sizes around 130 nm, and stable. Curcumin has been encapsulated in both types of nanoparticles without altering their colloidal properties. Moreover, SLNs greatly improve the solubility of MA and Curcumin. The cytotoxicity of MA and SLNs has been evaluated in BxPC3 human pancreatic cancer cells, MCF7 human breast cancer cells, and in a human fibroblast primary cell line. MA shows higher cytotoxic effect in BxPC3 and MCF7 cancer cells than in human primary fibroblasts. Nile Red loaded MA SLNs are quickly uptaken by BxPC3 and MCF7 cells, and show different cytoplasmic distributions depending on the cellular line. The oral or intravenous administration of MA SLNs in mice does not report any toxic effect, and the intravenous administration of fluorescent MA SLNs shows a homogeneous distribution in mice, without site-specific accumulation. Results suggest the great potential of MA SLNs as nanocarriers of anticancer drugs and as promising targeted theranostic nanodevices.

Scavenger receptor A-mediated nanoparticles target M1 macrophages for acute liver injury

Acute liver injury (ALI) has an elevated fatality rate due to untimely and ineffective treatment. Although, schisandrin B (SchB) has been extensively used to treat diverse liver diseases, its therapeutic efficacy on ALI was limited due to its high hydrophobicity. Palmitic acid-modified serum albumin (PSA) is not only an effective carrier for hydrophobic drugs, but also has a superb targeting effect via scavenger receptor-A (SR-A) on the M1 macrophages, which are potential therapeutic targets for ALI. Compared with the common macrophage-targeted delivery systems, PSA enables site-specific drug delivery to reduce off-target toxicity. Herein, we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI. In vitro, compared with human serum albumin encapsulated SchB nanoparticles (SchB-HSA NPs), the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide (LPS) stimulated Raw264.7 (LAR) cells, and LAR cells took up PSA NPs 8.79 times more than HSA NPs. As expected, the PSA NPs also accumulated more in the liver. Moreover, SchB-PSA NPs dramatically reduced the activation of NF-κB signaling, and significantly relieved inflammatory response and hepatic necrosis. Notably, the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%. Hence, SchB-PSA NPs are promising to treat ALI.

Hydrophobic Drug Carrier from Polycaprolactone-b-Poly(Ethylene Glycol) Star-Shaped Polymers Hydrogel Blend as Potential for Wound Healing Application.

Blending hydrogel with an amphiphilic polymer can increase the hydrophobic drug loading and entrapment efficiency of hydrogel-based formulations. In this study, a hydrogel formulation with star-shaped polycaprolactone-b-poly(ethylene glycol) (PCL-b-PEG) as the hydrophobic drug cargo is produced. The 4-arm and 6-arm star-shaped PCL are synthesized with different molecular weights (5000, 10,000, 15,000 g/mol) via ROP and MPEG as the hydrophilic segment is attached via the Steglich esterification. FTIR and 1H-NMR analysis showed the presence of all functional groups for homopolymers and copolymers. Mn for all synthesized polymers is close to the theoretical value while GPC spectra showed a monomodal peak with narrow molecular weight distribution (PDI:1.01-1.25). The thermal degradation temperature and crystalline melting point of synthesized polymers increase with the increase in molecular weight and number of arms. All formulations possess high drug loading and entrapment efficiency (>99%) and increase with increasing molecular weight, number of arms, and amount of polymer in the formulations. All formulations showed a sustained drug release pattern with no initial burst, which follows the Korsmeyer-Peppas kinetic model. The polymer hydrogel formulations showed antibacterial activity against E. coli and S. aureus. The hydrogel containing 4-arm PCL15k-PEG is chosen as the best formulation due to its high drug release, good antimicrobial activity, and morphology.

Solubilization mechanism of self-assembled walnut protein nanoparticles and curcumin encapsulation.

Native walnut protein is an alkali-soluble protein that seriously limits the application of walnut protein. The pH-shifting method could improve the solubility of walnut proteins and enable the encapsulation of active ingredients. The present study aimed to prepare water-soluble nanoparticles of curcumin using walnut protein and evaluate the process of walnut protein self-assembly, interaction between walnut protein and curcumin, encapsulation properties, and stability of nanoparticles. The solubility of native walnut protein was poor, but the solubility of walnut protein nanoparticles (WPNP) formed by walnut protein after pH-shifting significantly improved to 91.5 ± 1.2%. This is because, during the process of pH changing from 7 to 12 and back to 7, walnut protein first unfolded under alkaline conditions and then refolded under pH drive, finally forming an internal hydrophobic and external hydrophilic shell-core structures. The quenching type of walnut protein and curcumin was static quenching, and the quenching constant was 2.0 × 1014 mol-1 L-1 s-1 , indicating that the interaction between walnut protein and curcumin was non-covalent. Adding curcumin resulted in the formation of nanoparticles with small particle size compared with the no-load. The loading capacity of curcumin-loaded walnut protein nanoparticles (WPNP-C) was 222 mg g-1 walnut protein isolate. Under the same mass, the curcumin equivalent concentration in aqueous solution of WPNP-C was 17 000 times higher than that of the native curcumin. The solubility of the self-assembled WPNP significantly increased after pH-shifting treatment. The walnut protein carrier could improve the stability of the encapsulated curcumin. Therefore, walnut proteins could be used as water-soluble carriers for hydrophobic drugs. © 2023 Society of Chemical Industry.

Paclitaxel-Loaded Cationic Fluid Lipid Nanodiscs and Liposomes with Brush-Conformation PEG Chains Penetrate Breast Tumors and Trigger Caspase-3 Activation.

Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLsPTX) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLsPTX and PTX-containing fluid lipid nanodiscs (nanodiscsPTX). These CLsPTX and nanodiscsPTX show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol % PEG-lipid). Here, we studied the PTX loading, in vivo circulation half-life, and biodistribution of systemically administered CLsPTX and nanodiscsPTX and assessed their ability to induce apoptosis in triple-negative breast-cancer-bearing immunocompetent mice. We focused on fluid rather than solid lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol % of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLsPTX and nanodiscsPTX was able to incorporate up to 2.5 mol % PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol % PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol % (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration, and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy.

Hepatoma-targeting and reactive oxygen species-responsive chitosan-based polymeric micelles for delivery of celastrol

A glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) conjugate was designed and synthesized for the in vivo delivery of celastrol (Cela). Cela was encapsulated into polymeric micelles (PMs) formed by GCTR conjugates self-assembly in water to form Cela/GCTR PMs with high drug loading capacity and small particle size. Cela/GCTR PMs had a sustained-release characteristic in the blood environment and a rapid-release feature in the tumor microenvironment. Cela/GCTR PMs had a significant proliferation inhibitory effect on HepG2 and BEL-7402 cells, but a negligible impact on L-02 cells at low concentrations. Cela/GCTR PMs possessed reactive oxygen species (ROS)-responsive properties in vitro and in cells, could improve the bioavailability of Cela, and exert remarkable hepatoma-targeting properties. Cela/GCTR PMs could also effectively inhibit tumor growth with no apparent damage to different organs. In summary, GCTR PMs with good ROS-responsive and hepatoma-targeting properties are expected to be possible delivery carriers for hydrophobic antineoplastic drugs for hepatocellular carcinoma therapy.