Release Kinetics Of Doxorubicin Research Articles

Fabrication and characterization of doxorubicin conjugated bimetallic gold and platinum nanoparticles for human cancer cells and its cell death mechanism

An environmentally friendly preparation technique was used to explore the mechanism of action of hybrid hydrophilic bimetallic gold-platinum (Au@Pt-NPs) against human cancer cell lines, followed by conjugation with doxorubicin (DOX). The synthesized DOX-loaded Au@Pt-NPs (DOX/Au@Pt-NPs) were examined using transmission electron microscopy, X-ray diffraction, and UV–vis spectroscopy to determine their physicochemical characteristics. Using a straightforward incubation method, phytochemicals-mediated capping efficiency and loading of DOX onto the Au@Pt-NPs surface (84%) was demonstrated by FT-IR spectroscopy. Studies on the release kinetics of DOX under acidic tumor conditions revealed a pH-regulated dependence response. According to the in vitro anticancer assessment, human cancer cells treated with DOX-loaded Au@Pt-NPs demonstrated a 3-fold increase in apoptosis compared to DOX treatment alone. Additionally, the DOX/Au@Pt-NPs nanocarrier demonstrated a time-dependent increase in phosphatidylserine flipping, an apoptosis induction marker, and a cell-specific reaction in HeLa and HepG2 cells, according to luminescent results from a real-time, bioluminescent recombinant annexin V test. According to the results, the manufacturing process is simple, and the hydrophilic Au@Pt-NPs were successful in DOX delivery and loading against human cancer cell lines, indicating their prospective as a supplementary for cervical and hepatocellular cancer therapy.

Surface PEGylation of ZIF-8 metal-organic framework based on magnetic hydroxyapatite as a pH/magnetic targeting responsive system for anticancer drug delivery

In the present study, a zinc-based metal-organic framework/magnetic hydroxyapatite nanocomposite (Fe3O4@SiO2@HAp@ZIF-8) as new targeting drug delivery system was synthesized through the solvothermal method. Then, Fe3O4@SiO2@HAp@ZIF-8 was coated with a biocompatible layer of polyethylene glycol (PEG) (Fe3O4@SiO2@HAp@ZIF-8-PEG). The structural features of these nanocomposites were characterized using FT-IR, XRD, FE-SEM, EDX, TEM, Zeta potential, BET, and VSM analysis. The Fe3O4@SiO2@HAp@ZIF-8 and Fe3O4@SiO2@HAp@ZIF-8-PEG were applied as a carrier to encapsulate the doxorubicin (DOX) as an anticancer drug. The drug loading capacity and encapsulation efficiency of Fe3O4@SiO2@HAp@ZIF-8 and Fe3O4@SiO2@HAp@ZIF-8-PEG were 7.6, 76.09, 9.8, and 98.12%, respectively. Moreover, a drug release study revealed that both nanocomposites were pH-dependent because of the dissolution of HAp under acidic conditions. The release kinetics of DOX from the prepared nanocomposites at pH 5 also showed that the Korsmeyer-Peppas model was the best model to describe the release mechanism of DOX from prepared systems. The in vitro cell viability results showed that synthesized systems had no significant toxicity, while DOX-loaded systems had notable and higher toxicity against A549 human lung carcinoma cell lines. The DPPH tests also showed that the prepared Fe3O4@SiO2@HAp@ZIF-8-PEG nanocomposites have excellent antioxidant activity. Therefore, all obtained results clearly suggest that the as-prepared drug systems are potential and suitable candidates for targeted drug delivery applications.

Polyhedral oligomeric silsesquioxane (POSS)-modified citric-acid coated magnetic Fe3O4 nanoparticles for anticancer drug delivery

In this work, magnetic nanoparticles coated with citric acid (Fe3O4@Cit) were synthesized via co-precipitation strategy. Then, Fe3O4@Cit was modified with octa-aminopropyl polyhedral oligomeric silsesquioxane hydrochloride salt nanoparticles (OAPOSS NPs) by amidation reaction between carboxylic acid end groups on Fe3O4@Cit and the amine groups of OAPOSS surface (Fe3O4@Cit@OAPOSS). The key point of this approach is utilizing a symmetric nanosized cagelike POSS NPs as coating material to obtain novel hybrid drug nanocarrier. The successful preparation of nanocarrier (Fe3O4@Cit@OAPOSS) was confirmed by various techniques. Drug loading and release behaviors of Fe3O4@Cit@OAPOSS were evaluated using doxorubicin (DOX), a standard anticancer model drug, in neutral and acidic conditions. Moreover, Higuchi and Korsmeyer-Peppas models were used to study the release kinetics of DOX. Obtained results confirmed the suitability of Fe3O4@Cit@OAPOSS as a potential novel nanocarrier for drug delivery.

Mass transfer of anti‐cancer drug delivery to brain tumors by a multiple emulsion‐based implant

AbstractThe advanced use of a pH‐responsive biomaterial‐based injectable liquid implant for effective chemotherapeutic delivery in glioblastoma multiforme (GBM) brain tumor treatment is presented. As an implant, we proposed a water‐in‐oil‐in‐water multiple emulsion with encapsulated doxorubicin. The effectiveness of the proposed therapy was evaluated by comparing the cancer cell viability achieved in classical therapy (chemotherapeutic solution). The experimental study included doxorubicin release rates and consumption for two emulsions differing in drop sizes and structures in the presence of GBM‐cells (LN229, U87 MG), and a cell viability. The results showed that the multiple emulsion implant was significantly more effective than classical therapy when considering the reduction in cancer cell viability: 85% for the emulsion‐implant, and only 43% for the classical therapy. A diffusion–reaction model was adapted to predict doxorubicin release kinetics and elimination by glioblastoma cells. CFD (computational fluid dynamics) simulations confirmed that the drug release kinetics depends on multiple emulsion structures and drop sizes.

Dual Loading of Doxorubicin and Magnetic Iron Oxide into PLA-TPGS Nanoparticles: Design, in vitro Drug Release Kinetics, and Biological Effects on Cancer Cells.

The multifunctional nano drug delivery system (MNDDS) has much revolutionized in cancer treatment, aiming to eliminate many disadvantages of conventional formulations. This paper herein proposes and demonstrates MNDDS inspired by poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymer co-loaded Doxorubicin and magnetic iron oxide nanoparticles (MIONs) with a 1 : 1 (w/w) optimal ratio. In vitro drug release kinetics of Doxorubicin from this nanosystem fitted best to the Weibull kinetic model and can be described by the classical Fickian diffusion mechanism under acidic pH conditions. The combination of MIONs and Doxorubicin in the PLA-TPGS copolymer has maintained the fluorescence properties of Doxorubicin and good cell penetration, especially inside the nucleus and its vicinity. Moreover, different cell cycle profiles were observed in HeLa cell lines treated with MNDDSs.

Doxorubicin-Loaded PLGA Nanoparticles for Cancer Therapy: Molecular Weight Effect of PLGA in Doxorubicin Release for Controlling Immunogenic Cell Death.

Direct local delivery of immunogenic cell death (ICD) inducers to a tumor site is an attractive approach for leading ICD effectively, due to enabling the concentrated delivery of ICD inducers to the tumor site. Herein, we prepared doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using different molecular weight PLGA (7000 g/mol and 12,000 g/mol), showing different drug release kinetics. The different release kinetics of DOX might differently stimulate a tumor cell-specific immune response by releasing damage-associated molecular patterns (DAMPs), resulting in showing a different antitumor response in the living body. DOX-PLGA7K NPs showed faster DOX release kinetics than DOX-PLGA12K NPs in the physiological condition. DOX-PLGA7K NPs and DOX-PLGA12K NPs were successfully taken up by the CT-26 tumor cells, subsequently showing different DOX localization times at the nucleus. Released DOX successfully lead to cytotoxicity and HMGB1 release in vitro. Although the DOX-PLGA7K NPs and DOX-PLGA12K NPs showed different sustained DOX release kinetics in vitro, tumor growth of the CT-26 tumor was similarly inhibited for 28 days post-direct tumor injection. Furthermore, the immunological memory effect was successfully established by the ICD-based tumor-specific immune responses, including DC maturation and tumor infiltration of cytotoxic T lymphocytes (CTLs). We expect that the controlled release of ICD-inducible chemotherapeutic agents, using different types of nanomedicines, can provide potential in precision cancer immunotherapy by controlling the tumor-specific immune responses, thus improving the therapeutic efficacy.

Sodium Cholate Bile Acid-Stabilized Ferumoxytol-Doxorubicin-Lipiodol Emulsion for Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

PurposeTo develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC). Materials and MethodsFerumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models. ResultsDOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion. ConclusionsSC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.

Cell targeting strategy affects the intracellular trafficking of liposomes altering loaded doxorubicin release kinetics and efficacy in endothelial cells.

Targeting nanocarrier drug delivery systems, that deliver drug payloads to the site of disease action, are frequently viewed as the future of nanocarrier based therapies but have struggled to breakthrough to the clinic in comparison to non-targeting counterparts. Using unilamellar liposomes as model nanocarriers, we show that cell targeting strategy (electrostatic, ligand and antigen) influences both the intracellular fate of the liposomes and the corresponding efficacy of the loaded drug, doxorubicin, in endothelial cells. We show that increased liposome uptake by cells does not translate to improved efficacy in this scenario but that liposome intracellular trafficking, particularly distribution between recycling endosomes and lysosomes, influences in vitro efficacy. Choosing targeting strategies that promote desired nanocarrier intracellular trafficking may be a viable strategy to enhance the in vivo efficacy of drug delivery systems.

Chitosan Hydrogels for Synergistic Delivery of Chemotherapeutics to Triple Negative Breast Cancer Cells and Spheroids.

This study aimed to develop a hydrogel system for treating aggressive triple negative breast cancer (TNBC) via kinetically-controlled delivery of the synergistic drug pair doxorubicin (DOX) and gemcitabine (GEM). A 2D assay was adopted to evaluate therapeutic efficacy by determining combination index (CI), and a 3D assay using cancer spheroids was implemented to assess the potential for translation in vivo. The release of DOX and GEM from an acetylated-chitosan (ACS, degree of acetylation χAc = 40 ± 5%) was characterized to identify a combined drug loading that affords release kinetics and dose that are therapeutically synergistic. The selected DOX/GEM-ACS formulation was evaluated in vitro with 2-D and 3-D models of TNBC to determine the combination index (CI) and the tumor volume reduction, respectively. Therapeutically desired release dosages and kinetics of GEM and DOX were achieved. When evaluated with a 2-D model of TNBC, the hydrogel afforded a CI of 0.14, indicating a stronger synergism than concurrent administration of DOX and GEM (CI = 0.23). Finally, the therapeutic hydrogel accomplished a notable volume reduction of the cancer spheroids (up to 30%), whereas the corresponding dosages of free drugs only reduced growth rate. The ACS hydrogel delivery system accomplishes drug release kinetics and molar ratio that affords strong therapeutically synergism. These results, in combination with the choice of ACS as affordable and highly abundant source material, provide a strong pre-clinical demonstration of the potential of the proposed system for complementing surgical resection of aggressive solid tumors.

Formation of H2O2/temperature dual-responsive supramolecular micelles for drug delivery and kinetics

H2O2 and temperature dual-responsive supramolecular micelles were prepared from β-cyclodextrin-poly(N-isopropylacrylamide) (β-CD-PNIPAM) star polymer and ferrocene-modified polyethylene glycol (Fc-mPEG) due to the host–guest recognitions between cyclodextrin and ferrocene. The micelles with the size of about 100 nm were comprised of hydrophobic PNIPAM as the core and hydrophilic mPEG as the shell at the temperature above LCST. The supramolecular micelles exhibited reversible temperature and redox on–off switch feature. The hydrophobic micelles core and cavity of β-CD can effectively encapsulate doxorubicin (DOX) with the drug-loading content of 37.23% and entrapment efficiency of 74.45%. The drug-loaded micelles exhibited higher anti-cancer activity than free drugs. The ferrocene group was oxidized into ferrocene ions when H2O2 was added, resulting in the dissociation of supramolecular micelles and acceleration of drug release. Release kinetics of DOX conforms to oxidation controlled mechanism with H2O2 and Fickian diffusion-controlled mechanism with temperature.

Doxorubicin conjugated hydrophilic AuPt bimetallic nanoparticles fabricated from Phragmites australis: Characterization and cytotoxic activity against human cancer cells

In this study, a hybrid hydrophilic bimetallic gold-platinum (AuPtNPs) was prepared via an eco-friendly method and then conjugated with doxorubicin (DOX) to investigate their mechanism of action against human cancer cell lines. The physicochemical properties of the prepared DOX-loaded AuPtNPs (DOX@AuPtNPs) were investigated using UV–vis spectroscopy, transmission electron microscopy, and X-ray diffraction. Fourier transform infrared spectroscopy revealed phytochemicals-based efficient capping and loading of DOX onto the AuPtNPs surface (83%) via a simple incubation technique. DOX release kinetics studies indicated a pH-controlled dependency response under acidic tumor condition. The in vitro anticancer evaluation showed that the DOX-loaded AuPtNPs induced a three-fold cell death to human cancer cells compared to DOX alone. Moreover, the luminescent data from a real-time, bioluminescent recombinant annexin V assay indicated that the DOX@AuPtNPs nanocarrier exhibited a time-released phosphatidylserine exposure; an apoptosis induction marker and cell-specific response against MCF-7 cells compared to A459 cells. The results suggested that the preparation method is facile, and the prepared hydrophilic AuPtNPs proved effective in DOX loading and delivery against human cancer cells therefore, demonstrating potential as an alternative cancer treatment.

Sterically Stabilised Polymeric Mesoporous Silica Nanoparticles Improve Doxorubicin Efficiency: Tailored Cancer Therapy.

The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are attractive nanocarriers due to their biodegradable, biocompatible, and relative malleable porous frameworks that can be functionalized for enhanced targeting and delivery in a variety of disease models. The optimal formulation of an MSN with polyethylene glycol (2% and 5%) and chitosan was undertaken, to produce sterically stabilized, hydrophilic MSNs, capable of efficient loading and delivery of the hydrophobic anti-neoplastic drug, doxorubicin (DOX). The pH-sensitive release kinetics of DOX, together with the anticancer, apoptosis and cell-cycle activities of DOX-loaded MSNs in selected cancer cell lines were evaluated. MSNs of 36–60 nm in size, with a pore diameter of 9.8 nm, and a cumulative surface area of 710.36 m2/g were produced. The 2% pegylated MSN formulation (PCMSN) had the highest DOX loading capacity (0.98 mgdox/mgmsn), and a sustained release profile over 72 h. Pegylated-drug nanoconjugates were effective at a concentration range between 20–50 μg/mL, inducing apoptosis in cancer cells, and affirming their potential as effective drug delivery vehicles.

Incorporation of doxorubicin in different polymer nanoparticles and their anticancer activity.

Background: Nanoparticles are under investigation as carrier systems for anticancer drugs. The expression of efflux transporters such as the ATP-binding cassette (ABC) transporter ABCB1 is an important resistance mechanism in therapy-refractory cancer cells. Drug encapsulation into nanoparticles has been shown to bypass efflux-mediated drug resistance, but there are also conflicting results. To investigate whether easy-to-prepare nanoparticles made of well-tolerated polymers may circumvent transporter-mediated drug efflux, we prepared poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) nanoparticles loaded with the ABCB1 substrate doxorubicin by solvent displacement and emulsion diffusion approaches and assessed their anticancer efficiency in neuroblastoma cells, including ABCB1-expressing cell lines, in comparison to doxorubicin solution.Results: The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement led to the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH 7 reaching 53 µg doxorubicin/mg nanoparticle. These PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH 7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anticancer effects. However, nanoparticle-encapsulated doxorubicin did not display increased efficacy in ABCB1-expressing cells relative to doxorubicin solution.Conclusion: Doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anticancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anticancer efficacy. The design of drug-loaded nanoparticles with optimised anticancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anticancer therapy. Further research is required to understand under which circumstances nanoparticles can be used to overcome efflux-mediated resistance in cancer cells.

The influence of cross-linking agent onto adsorption properties, release behavior and cytotoxicity of doxorubicin-imprinted microparticles

Molecularly imprinted polymers (MIPs) are synthetic polymers that possess cavities selective towards their molecular templates and have found many applications in separation science, drug delivery, and catalysis. Here, we report the synthesis of doxorubicin-imprinted microparticles cross-linked with two different compounds (ethylene glycol dimethacrylate or trimethylolpropane trimethacrylate) and examination of their physicochemical properties. During the synthesis methacrylic acid was used as functional monomer and 2-hydroxyethyl methacrylate was added into polymerization mixture to increase hydrophilicity of the obtained materials and therefore improve interactions with aqueous release medium. The influence of initial concentration and contact time onto doxorubicin adsorption by obtained MIPs microparticles have been investigated. The microparticles obtained using ethylene glycol dimethacrylate as a cross-linker showed 3 times higher adsorption properties towards doxorubicin, than the ones obtained using trimethylolpropane trimethacrylate cross-linker. The release kinetics of doxorubicin from drug-loaded MIPs microparticles has been proven to be dependent upon cross-linker used and pH of the release medium. For drug-loaded MIPs microparticles obtained using both cross-linkers the IC50 values measured for cancer cell were comparable to the ones measured for pure doxorubicin, whereas the cytotoxicity towards normal HDF cell lines was lower.

Effects of polymer chemistry, concentration, and pH on doxorubicin release kinetics from hydroxyapatite-PCL-PLGA composite

Abstract

Green synthesized amino-PEGylated silver decorated graphene nanoplatform as a tumor-targeted controlled drug delivery system

In this study design, the PEGylated silver decorated graphene nanocomposites (NGO-AgNPs-PEG) were successfully prepared by eco-friendly non-toxic green synthesis following a novel syn-graphenization method using the aqueous leaf extract of Azadirachta indica (A. indica) (neem) as reducing agent. The prepared Smart pH stimuli responded nanoplatform was thoroughly characterized by various analytical techniques. Since a functional nanocarrier is very essential for cancer therapy, it could quickly guide the loaded anticancer drug to the tumor site to decrease the side effect. In order to overcome the side effects of doxorubicin (DOX), an anticancer drug, it was incorporated into amino PEGylated NGO-AgNPs nanocomposites. Considering drug loading and release studies, it may be concluded that improved drug loading efficiency (218%) and more pH-responsive controlled release (following Korsmeyer–Peppas model release kinetics) of DOX from NGO-AgNPs-PEG lead to a promising nanocarrier for the anticancer drug. The cytotoxicity study results, on HaCaT cell lines, indicated DOX-loaded PEGylated functionalized nanographene oxides, as compared to free DOX, had lesser harmful effect on normal cells than cancer cells. Increased cytotoxicity was exhibited in the cancerous cells (HeLa cell lines) treated with DOX loaded PEGylated silver functionalized nanographene oxide compared to covalently conjugated NGO-DOX. So, the effective delivery and release of the anticancer drug into acidic microenvironment of the targeted tumour cells would bring out higher therapeutic efficacy than pure NGO. Such a gold standard biocompatible PEGylated silver decorated NGO theranostic nanoplatform may be an excellent nano cargo for targeted and controlled drug delivery in cancer therapy.

Preclinical evaluation of thermosensitive poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-grafted liposomes for cancer thermochemotherapy

Thermosensitive liposomes grafted with cholesterol-conjugated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) (chol-pHPMAlac) have been developed for heat-induced release of doxorubicin (DOX). These liposomes release DOX completely during mild hyperthermia, but their interaction with blood cells and cancer cells has not been studied. Following intravenous administration, liposomes may interact with plasma proteins and various types of cells (e.g., endothelial cells, platelets, and macrophages), which would reduce their disposition in the tumor stroma. Interaction between liposomes and platelets may further cause platelet activation and thrombosis, which could lead to vascular occlusion and thromboembolic complications. The aim was to investigate DOX release kinetics in the presence of serum, stability, in vitro uptake by and toxicity to cancer cells and somatic cells, and platelet activating potential of the chol-pHPMAlac liposomes. DOX release was determined spectrofluorometrically. Liposome stability was determined in buffer and serum by dynamic light scattering and nanoparticle tracking analysis. Association with/uptake by and toxicity of empty liposomes to AML-12, HepG2 (both hepatocyte-derived cancer cells), RAW 264.7 (macrophages), and HUVEC (endothelial) cells was assayed in vitro. Platelet activation was determined by analysis of P-selectin expression and fibrinogen binding. DOPE:EPC liposomes (diameter = 135 nm) grafted with 5% chol-pHPMAlac (cloud point (CP) = 16 °C; Mn = 8.5 kDa) released less than 10% DOX at 37 °C in 30 min, whereas complete release took place at 47 °C or higher within 10 min. The size of these liposomes remained stable in buffer and serum during 24 h at 37 °C. Fluorescently labeled but DOX-lacking chol-pHPMAlac-liposomes exhibited poor association with/uptake by all cells under investigation, were not cytotoxic, and did not activate platelets in both buffered solution and whole blood. In conclusion, thermosensitive chol-pHPMAlac-grafted liposomes rapidly release DOX during mild hyperthermia. The liposomes are stable in a physiological milieu, are not taken up by cells that are encountered in an in vivo setting, and are non-antagonistic towards platelets. Chol-pHPMAlac-grafted liposomes are therefore good candidates for DOX delivery to tumors and temperature-triggered release in tumor stroma.

Supramolecular poly(N-acryloylmorpholine)-b-poly(d,l-lactide) pseudo-block copolymer via host-guest interaction for drug delivery

In the present study, a pseudo-block copolymer was prepared from β-cyclodextrin terminated poly(N-acryloylmorpholine) (β-CD-PNAM) and adamantine-terminated linear poly(D,L-lactide) (AD-PDLLA), through host-guest interaction between β-CD and AD groups. Initially, the hydrophilic polymer PNAM was synthesized using reversible addition fragmentation polymerization, which was further linked to N3-β-CD through click reaction. In parallel, an AD terminated hydrophobic polymer, AD-PDLLA was synthesized using ring opening polymerization. The synthesized polymers were characterized by means of 1H NMR, gel permeation chromatography and fourier transform infrared. Subsequently, the formation of a pseudo-block copolymer via inclusion complexation between the β-CD core and AD-moiety was confirmed by 2D-NOESY NMR and self-aggregation of the pseudo-block copolymer was investigated by fluorescence spectroscopy. In addition, doxorubicin (DOX) a hydrophobic drug was loaded into the supramolecular micelles and the release kinetics of DOX from the micelles was studied. The result revealed that DOX release was accelerated as the pH reduced from 7.4 to 6.4.

Combining ultrasound and intratumoral administration of doxorubicin-loaded microspheres to enhance tumor cell killing

Melanoma is an incurable disease for which alternative treatments to chemotherapy alone are sought. Here, using a melanoma model, we investigated the antitumor potential of combining ultrasound (US) with poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with doxorubicin (DOX). The aim was to achieve synergistic tumoricidal activity through direct and indirect US-mediated damage of tumor cells combined with sustained and potentially controllable release (when combined with US) of DOX from microspheres. An in vitro release assay demonstrated an ability of US to affect the release kinetics of DOX from DOX-loaded PLGA microspheres by inducing a 12% increase in the rate of release. In vitro viability assays demonstrated that combining US with DOX-loaded PLGA microspheres resulted in synergistic tumor cell (B16-F10 melanoma cells) killing. Melanoma-bearing mice were treated intratumorally with DOX (8 µg)-loaded microspheres and subjected to US treatment at the tumor site. This treatment could significantly extend survival (mean survival (MS) = 22.1 days) compared to untreated mice (MS = 10.4 days) and most other treatments, such as blank microspheres plus US (MS = 11.5 days) and DOX (8 µg)-loaded microspheres alone (MS = 13 days). The findings that immune checkpoint blockade did not significantly extend survival of mice treated with DOX (8 µg)-loaded microspheres plus US, and that tumor-free (“cured”) mice were not protected from subsequent tumor rechallenge suggests minimal involvement of the adaptive immune response in the observed antitumor activity. Nevertheless, the synergistic increase in survival of melanoma-challenged mice treated with the combination of US and DOX-loaded microspheres implicates such a treatment methodology as a promising additional tool for combatting otherwise currently incurable cancers.

Graphene oxide@gold nanorods for chemo-photothermal treatment and controlled release of doxorubicin in mice Tumor

Graphene oxide (GO) is a close derivative of graphene has unlocked many pivotal steps in drug delivery due to their inherent biocompatibility, excellent drug loading capacity, and shows antibacterial, antifungal properties etc. We used a novel plant material called Gum arabic (GA) to increase the solubility of GO as well as to chemically reduce it in the solution. GA functionalized GO (fGO) exhibited increased absorption in near infra-red region (NIR) which was exploited in photothermal therapy for cancer. In order to understand the shape and size effect of GO which may affect their rheological properties, we have conjugated them with gold nanorods (GNRs) using in situ synthesis of GO@GNRs via seed mediated method. To the above conjugate, Doxorubicin (DOX) was attached at ambient temperature (28±2°C). The release kinetics of DOX with the effect of NIR exposure was also carefully studied via in vitro photothermal killing of A549 cell lines. The enhancement in NIR induced drug release and photothermal property was observed which indicates that the fGO@GNRs-DOX method is an ideal choice for chemotherapy and photothermal therapy simultaneously.