Encapsulation Of Dox Research Articles

Development polymeric micellar system for targeted delivery of antitumor drugs

Asymmetric block copolymers PAAc-b-PAAm (DBC) and PAAm-b-PAAc-b-PAAm (TBC) comprised poly(acrylic acid) and polyacrylamide have been evaluated as potential vehicles for doxorubicin (Dox) targeted delivery. The processes of Dox release from the DBC and TBC micelles under the influence of the drug’s concentration gradient and various surrounding medium, such as NaCl solution and aqueous medium at pH= 5.75 and 9, were examined. The previously established tendency to significantly reduce the Dox encapsulation degree by the DBC and TBC micelles at the increase of the size of their “corona” was fully confirmed (Kunitskaya et al. 2018). Noticed that PAAm block’s lengthening complicated the Dox release against all environments under study. It was revealed that micelles which easily and effectively encapsulate Dox as easily "give away" the drug during dialysis. Increasing pH of the DBC and TBC solutions to 9 prevented drug release. It can be stipulated by enhancing interaction between Dox and micellar “core” caused by the ionization of –COOH groups contained in PAAc blocks. Preliminary biological investigations in vitro against human T-leukemia cells demonstrate essential anticancer activity of Dox/DBC and Dox/TDC compositions, as compared to pure Dox.

Development of a multifunctional system based on CoFe2O4@polyacrylic acid NPs conjugated to folic acid and loaded with doxorubicin for cancer theranostics

In this work, a multifunctional theranostic nanocomposite based on CoFe2O4@polyacrylic acid (PAA)-Folic Acid (FA) Doxorubicin (Dox)load NPs was designed for the multifunctional cancer treatment. Several techniques such as TEM, DLS, ζ-potential, vibrating sample magnetometer, XRD, and UV−Vis spectrophotometer were applied for investigating physicochemical properties of the nanosystem. The percentage of the loaded drug, loading efficiency, in vitro release (pH 5.4 and 7.4), in vitro MRI measurements, and MTT assay (4T1 and 9A9 cell lines) were evaluated. Results showed that the percentage of loaded drug and loading efficiency was 53.33 ± 3.5 and 80.00 ± 5.3%, respectively, showing the system’s high ability for Dox encapsulation. Release study showed that Dox loaded in the CoFe2O4@PAA-FA(Dox)load NPs released faster at pH 5.4 than pH 7.4. In vitro, MRI measurements confirmed that CoFe2O4@PAA NPs could be used as a contrast agent in MRI measurements with r 2 = 18.2 mM−1 s−1. MTT assay demonstrated the biocompatibility of NPs, also showed a more efficient therapeutic effect for CoFe2O4@PAA-FA(Dox)load NPs than free Dox and CoFe2O4@PAA(Dox)load NPs.

Co-delivery of cisplatin and doxorubicin by carboxylic acid functionalized poly (hydroxyethyl methacrylate)/reduced graphene nanocomposite for combination chemotherapy of breast cancer cells

In this study a novel pH-responsive magnetic nanocomposite based on reduced graphene oxide was developed for combination of doxorubicin (Dox)-cisplatin (Cis) delivery to destroy the MCF-7 cell line. For this purpose, polyhydroxyethyl methacrylate (PHEMA) was bonded to the reduced graphene oxide through ATRP polymerization using grafting from method. Then the PHEMA hydroxy groups were converted to succinyloxy groups by polyesterification with succinic anhydride. The physicochemical properties of the nanocomposite were investigated via FTIR, SEM, XRD, DLS and TGA analysis. Unique structure of nanocomposite led to simultaneous encapsulation of Dox (75%) and Cis (82%) through ionic interaction, π–π stacking and hydrogen bonding. The obtained nanocomposite was uptake by MCF-7 cells at early first hour because of nanocomposite small size (below 70 nm). Cell viability assay results revealed that the Dox&Cis-loaded nanocomposite showed the highest rate of MCF-7 cells at lowest concentration (IC50 = 0.798 µg/mL) compared to treatment groups received single drug-loaded nanocomposite and free drugs. Dox&Cis-loaded nanocomposite exhibited a synergistic influence with the combination index (CI) value <1. The cell cycle analysis results revealed that the highest amount of apoptosis (cells population in sub G1 was 75%) was observed in the Dox&Cis-loaded nanocomposite treatment group compared with the single drug-loaded nanocomposite and free drugs. Our findings confirmed that combinational therapy by Dox and Cis graphene oxide-based nanocomposite has increased the cytotoxicity in MCF-7 cells by stimulating the apoptotic response.

Oleanolic acid-conjugated poly (D, l-lactide)-based micelles for effective delivery of doxorubicin and combination chemotherapy in oral cancer

Here, an amphiphilic polymer, oleanolic acid conjugated methoxy-poly (ethylene glycol)-poly (D, l-lactide) (mPEG-PLA-OA) was synthesized, which self-assembled in aqueous environment and loaded the poorly soluble anticancer agent, doxorubicin. Various physico-chemical characterization studies on polymer and DOX-loaded polymeric micelles (DOX-mPEG-PLA-OA) at various drug to polymer (1:5/10/15) (DTP) ratios were performed, which included characterizations via UV, IR, NMR spectroscopy and gel permeation chromatography for polymers, and dynamic light scattering, DSC, XRD techniques, determination of critical micelles concentration, percent drug loading, encapsulation efficiency, drug release, kinetic stability and haemolysis studies for micelles. Further, DOX-mPEG-PLA-OA were evaluated for their cellular uptake, cytotoxicity, ability to induce apoptosis, DNA fragmentation, nuclear damage, ROS generation, and mitochondrial membrane depolarization in oral squamous cell carcinoma (FaDu HTB-43) and murine melanoma (B16F10) in monolayer and in FaDu HTB-43 3D cell culture systems. DOX-mPEG-PLA-OA at DTP ratios. 1:5/10/15 showed physico-chemical parameters in the following range: particle sizes. ~210.3–225.1 nm, DOX encapsulation efficiency. 29–35% and DOX-loading. 2.2–5%. DOX-mPEG-PLA-OA micelles (1:15) were stable as proven by kinetic stability study, and showed sustained release of encapsulated DOX for over 60 h. The cell viability study revealed that DOX-mPEG-PLA-OA micelles (1:15) demonstrated highest time- and dose dependent cytotoxicity compared to free DOX and micelles of other DTP ratios. Following treatment, the DOX-mPEG-PLA-OA micelles (1:5/10/15) induced highest cellular apoptosis in the range of 28.17–48.1, compared to free DOX (9.5 ± 2.52), and mPEG-PLA-OA micelles (25.4 ± 2.91), DOX-mPEG-PLA-OA micelles (1:15) being the strongest apoptosis inducer (48.1 ± 2.68) as determined by flow cytometry-mediated annexin V assay. DOX-mPEG-PLA-OA micelles (1:15) induced significantly higher DNA fragmentation, nuclear condensation, ROS generation, and mitochondrial membrane permeabilization compared to free Dox in monolayer FaDu HTB-43. DOX-mPEG-PLA-OA micelles (1:15) showed reasonably higher penetration and stronger growth inhibition in FaDu HTB-43 spheroids compared to free DOX and micelles of other DTP ratios. In-vivo pharmacokinetic studies showed that the DOX-mPEG-PLA-OA micelles demonstrated enhanced blood circulation time with decreased rate of clearance than free Dox (t1/2. 33.5 ± 2.5 h vs. 1.77 ± 0.32 h, and Cmax. 59.7 ± 2.2 vs. 2.3 ± 0.1, respectively). Immunohistochemistry revealed no significant toxicity in major organs of DOX-mPEG-PLA-OA micelles treated rats. The series of studies indicated that the OA-conjugated mPEG-PLA micelles served as an efficient nanocarriers for DOX, demonstrated DOX, and OA combined superior anticancer effect, sustained DOX level in blood circulation for up to 96 h, and no sign of major organs toxicity. Therefore, this newly developed DOX, OA combined micelles displayed its potential as promising alternative to DOX-based conventional therapy, and warrants further investigation for clinical application, especially for the treatment of oral cancer.

Tragacanth gum‐based pH‐responsive magnetic hydrogels for “smart” chemo/hyperthermia therapy of solid tumors

The drug delivery performances of pH‐responsive magnetic hydrogels (MHs) composed of tragacanth gum (TG), poly(acrylic acid) (PAA), and Fe3O4 nanoparticles (NPs) were investigated in terms of physicochemical as well as biological features. The fabricated drug delivery systems (DDSs) were analyzed using Fourier transform infrared spectroscopy, X‐ray diffraction, vibrating sample magnetometer, scanning electron microscopy, and transmission electron microscopy. The synthesized MHs were loaded with doxorubicin hydrochloride (Dox) as a universal model anti‐cancer drug. The MHs showed excellent Dox loading and encapsulation efficiencies, mainly due to strong hydrogen bonding and electrostatic interaction between the drug and polymeric matrix, as well as porous micro‐structures of the fabricated MHs. The drug‐loaded MHs showed negligible drug release values in physiological condition. In contrast, in cancerous condition (pH 5.0), both MHs exhibited highest drug release values that qualified them as “smart” DDSs. The cytocompatibilities of the MHs as well as the cytotoxicity of the Dox‐loaded MHs were investigated against human epidermoid‐like carcinoma (Hela) cells through MTT assay. In addition, hyperthermia therapy induced by Fe3O4 NPs was applied to locally raise temperature inside the Hela cells at 45 ± 3°C to promote cell death. As a result, the Dox‐loaded MHs can be considered as potential DDSs for chemo/hyperthermia therapy of solid tumors.

Facile Ultrasound-Triggered Release of Calcein and Doxorubicin from Iron-Based Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) are promising new nanocarriers with potential use in anticancer drug delivery. However, there is a scarcity of studies on the uptake and release of guest molecules associated with MOF nanovehicles, and their mechanism is poorly understood. In this work, newly developed iron-based MOFs, namely Fe-NDC nanorods, were investigated as potential nanocarriers for calcein (as a model drug/dye) and Doxorubicin (a chemotherapeutic drug (DOX)). Calcein was successfully loaded by equilibrating its solution with the MOFs nanoparticles under constant stirring. The calcein average encapsulation efficiency achieved was 43.13%, with a corresponding capacity of 17.74 wt.%. In-vitro calcein release was then carried out at 37°C in phosphate buffer saline (PBS) using ultrasound (US) as an external trigger. MOFs released an average of 17.8% (without US), whereas they released up to 95.2% of their contents when 40-kHz US at ~1 W/cm² was applied for 10 min. The Cytotoxic drug DOX was also encapsulated in Fe-NDC, and its In-vitro release profile was determined under the same conditions. DOX encapsulation efficiency and capacity were found to be 16.10% and 13.37 wt.%, respectively. In-vitro release experiments demonstrated significant release, reaching 80% in 245 minutes, under acoustic irradiation, compared to around 6% in the absence of US. Additionally, experimental results showed that Fe-NDC nanoparticles are biocompatible even at relatively high concentrations, with an MCF-7 IC50 of 1022 g/ml. Our work provides a promising platform for anticancer drug delivery by utilizing biocompatible Fe-NDC nanoparticles and US as an external trigger mechanism.

Incorporation of Hydroxyapatite/Doxorubicin into the Chitosan/Polyvinyl Alcohol/Polyurethane Nanofibers for Controlled Release of Doxurubicin and Its Anticancer Property

In the present study, the doxorubicin-hydroxyapatite (DOX-HAp) has been loaded into the chitosan/PVA/PU single layer and core-shell nanofibers. The potential of synthesized nanofibers was evaluated for controlled release of DOX and bone cancer treatment in vitro. The synthesized DOX-HAp nanohybrid was characterized using XRD, SEM, and UV-Vis analysis. The morphology of synthesized nanofibers was examined by SEM and TEM analysis. For single layer nanofibers, some DOX-HAp nanohybrids were observed on the nanofibers surface. The fiber diameter was increased by increasing shell flow rate and no DOX-HAp nanohybrids were detected on the core-shell fibers surface. The DOX encapsulation efficiency of single layer and core-shell layer fibers was higher than 90 %. The initial burst release from single layer fiber at initial hours and the continuous release of DOX was observed from single layer nanofibers during 7 and 10 days under acidic and physiological pH. The sustained release of DOX was obtained within 10 and 14 days, 15 and 18 days, 21 and 25 days from core-shell fibers with flow rates of 0.3, 0.5 and 0.8 ml/h under acidic and physiological pH. The non-Fickian diffusion and Fickian diffusion were achieved from single layer and core-shell nanofibers. The cell attachment and cell death results indicated the high potential of DOX loaded-core-shell fibers for bone cancer treatment.

Preparation and Evaluation of Doxorubicin-Loaded PLA-PEG-FA Copolymer Containing Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for Cancer Treatment: Combination Therapy with Hyperthermia and Chemotherapy.

BackgroundAmong the novel cancer treatment strategies, combination therapy is a cornerstone of cancer therapy.Materials and MethodsHere, combination therapy with targeted polymer, magnetic hyperthermia and chemotherapy was presented as an effective therapeutic technique. The DOX-loaded PLA–PEG–FA magnetic nanoparticles (nanocarrier) were prepared via a double emulsion method. The nanocarriers were characterized by particle size, zeta potential, morphology, saturation magnetizations and heat generation capacity, and the encapsulation efficiency, drug content and in-vitro drug release for various weight ratios of PLA:DOX. Then, cytotoxicity, cellular uptake and apoptosis level of nanocarrier-treated cells for HeLa and CT26 cells were investigated by MTT assay, flow cytometry, and apoptosis detection kit.Results and ConclusionsThe synthesized nanoparticles were spherical in shape, had low aggregation and considerable magnetic properties. Meanwhile, the drug content and encapsulation efficiency of nanoparticles can be achieved by varying the weight ratios of PLA:DOX. The saturation magnetizations of nanocarriers in the maximum applied magnetic field were 59/447 emu/g and 28/224 emu/g, respectively. Heat generation capacity of MNPs and nanocarriers were evaluated in the external AC magnetic field by a hyperthermia device. The highest temperature, 44.2°C, was measured in the nanocarriers suspension at w/w ratio 10:1 (polymer:DOX weight ratio) after exposed to the magnetic field for 60 minutes. The encapsulation efficiency improved with increasing polymer concentration, since the highest DOX encapsulation efficiency was related to the nanocarriers’ suspension at w/w ratio 50:1 (79.6 ± 6.4%). However, the highest DOX loading efficiency was measured in the nanocarriers’ suspension at w/w ratio 10:1 (5.14 ± 0.6%). The uptake efficiency and apoptosis level of nanocarrier-treated cells were higher than those of nanocarriers (folic acid free) and free DOX-treated cells in both cell lines. Therefore, this targeted nanocarrier may offer a promising nanosystem for cancer-combined chemotherapy and hyperthermia.

Harnessing CD47 mimicry to inhibit phagocytic clearance and enhance anti-tumor efficacy of nanoliposomal doxorubicin

ABSTRACT Background We hypothesized if phagocytosis of liposomes by macrophages could be mitigated through incorporation of a CD47 mimicry peptide (Self peptide: SP) on the surface of liposomes. Methods Thin film hydration method followed by extrusion was used to prepare nanoliposomes, and Dox encapsulation in liposomes was done via remote-loading method. Decorated liposomes with SP peptide (SP-LD) at different peptide densities (300 and 600 peptides on the surface of each liposome) were prepared using a pre-insertion technique. Macrophage cell lines were used to compare the cellular uptake of decorated and unmodified liposomes. For biodistribution studies, tumor-bearing mice received the preparations, and fluorescence signals of Dox in different tissues were measured. To evaluate anti-tumor efficacy, tumor size and survival rates were assessed. Also, pharmacokinetic parameters were determined. Results Compared with PEGylated liposomes, uptake by macrophages was largely decreased when SP was incorporated on liposomes. Following intravenous injection, SP-liposomes were cleared more slowly compared with PEGylated liposomes. Eventually, SP-liposomes were highly distributed to tumor tissues compared with PEGylated liposomes, and significantly reduced tumor size and improved the survival of tumor-bearing mice. Conclusions This research showed reduced macrophage uptake, increased blood circulation, and enhanced tumor accumulation of liposomes through SP incorporation on the surface of particles.

Importance of the fatty acid chain length on in vitro and in vivo anticancer activity of fattigation-platform albumin nanoparticles in human colorectal cancer xenograft mice model

The aims of this study were to design different chain length fatty acid-conjugated albumin nanoparticles (ANPs) and evaluate their anticancer activity in the HCT116 human colorectal cancer xenograft mouse model. Doxorubicin hydrochloride (DOX·HCl) was chosen as a model drug. The different chain lengths of fatty acids (butyric acid; C4, and stearic acid; C18) in albumin conjugates exhibited different physicochemical properties and anticancer activity. Fatty acid-conjugated albumin aided the formation of self-assembled structures with an average size of approximately 200 nm and a negative charge when incubated with excess DOX in an aqueous solution. DOX-loaded long-chain C18-conjugated ANPs allowed efficient encapsulation of hydrophobic DOX into the core of the self-assembled structure, enabling higher drug loading, enhanced colloidal stability and controlled release behavior in PBS pH 7.4 medium as compared with free DOX·HCl or non-fatty acid conjugated ANPs. Furthermore, DOX-loaded fatty acid-conjugated ANPs showed an increased cellular uptake intensity and cytotoxic effects in vitro. In vivo, HCT116 xenograft model experiments confirmed that DOX-loaded C18-conjugated ANPs showed improved anticancer activity and reduced side effects compared with the DOX-treated groups. The long-chain fatty acid-conjugated ANPs synergistically activated the interaction with the free-fatty acid receptor (FFAR) on HCT116 colorectal cancer cells as compared with short-chain C4 or other non-conjugated ANPs. Specifically, DOX-loaded C18-conjugated NPs exhibited significant performance to overexpressed FFAR4 on HCT116 colorectal cancer cells. The fatty acid chain length in the fattigation-platform system could be a promising molecular moiety to improve targeting efficiency and drug accumulation in various cancer therapy.

Alginate-coated caseinate nanoparticles for doxorubicin delivery: Preparation, characterisation, and in vivo assessment

Natural protein-based nanoparticles are promising nano-vehicles for the delivery of chemotherapeutic drugs. Caseinate nanoparticles loaded with doxorubicin (CasNPs-DOX) have been surface-modified with the natural polysaccharide alginate to generate the novel nanocarrier Alg-CasNPs-DOX. The fabricated nanoparticles have been characterised by transmission electron microscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, fluorescence spectroscopy, and zeta potential measurement. Drug encapsulation and release profiles were also investigated. In vivo studies were conducted to evaluate the therapeutic efficacy of this novel drug delivery system in tumour-bearing mice. The biodistribution and toxicity of the nano-formulation were also assessed. The results showed that encapsulation of DOX in Alg-CasNPs-DOX not only led to controlled and sustained drug release but also significantly enhanced the effectiveness of DOX against Ehrlich carcinoma. Moreover, no significant changes were observed in liver and kidney enzymes, indicating the selective delivery of DOX to the tumour site, thus minimising DOX toxicity to certain vital organs. Accordingly, Alg-CasNPs-DOX was shown as a promising DOX nanocarrier for improving the therapeutic efficacy of DOX against cancer compared to that of free DOX.

Boron nitride nanotube clusters and their hybrid nanofibers with polycaprolacton: Thermo-pH sensitive drug delivery functional materials

Electrospinning-electrospraying is a promising technique in synthesis of hybrid polymeric materials for many applications, especially for drug delivery purposes. Since one of the most worrisome adverse effects of anticancer drugs such as doxorubicin (Dox), cisplatin and Fluorouracil (5FU) is cardiotoxicity, finding a possible novel strategy to prevent or manage this lethal side effect should be considered as one of the most important issues for investigation. In this study, we fabricated a fibrous scaffold containing encapsulated Dox to prevent Dox-induced cardiomyopathy with limited clinical use and improve clinical outcomes of chemotherapy in cancer patients. Simultaneous electrospinning-electrospraying was used to produce hybrid nanofibers intended to be used for controlled releases of doxorubicin. Boron nitride nanotubes (BNNTs) clusters were synthesized and employed for encapsulation of Dox and then they were subjected to electrospraying. Electrospinning of polycaprolactone (PCL) solution was performed simultaneously to provide a nanofiber network substrate for BNNT/Dox nanocapsules. Polycaprolactone nanofibers with average diameters at the range of 240 ± 55–450 ± 50 nm were synthesized depending on various electrospinning conditions. BNNTs/Dox homogenous solution in methanol/acetone (50/50 V/V) was prepared and electrosprayed on the surface of the nanofibers. Different properties of the produced electrospun mats such as morphology, thermal characteristics and in vitro drug releases were investigated. The results revealed the excellent thermo-pH sensitivity of the prepared BNNTs/PCL functional nano-mats.

GSH-responsive curcumin/doxorubicin encapsulated Bactrian camel serum albumin nanocomposites with synergistic effect against lung cancer cells.

The aim of this study was to prepare camel serum albumin (CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin (CCM) and doxorubicin (Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian ( Camelus bactrianus) CSA. The constructed CSA nanoparticles (CSA-NPs) with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite (CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione (GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drug-delivery matrix to exert synergistic effects.

Synthesis of β-cyclodextrin-PEG-G molecules to delay tumor growth and application of β-cyclodextrin-PEG-G aggregates as drug carrier

The clinical use of many chemotherapeutic drugs is considerably greatly limited due to their serious side effects. This problem can be solved by using a low-toxic or nontoxic drug carrier that exhibits excellent performance in entrapping chemotherapeutic drugs. Accordingly, β-cyclodextrin-PEG-guanosine (β-CD-PEG-G) molecule was first synthesized. The molecules can self-assemble into negatively charged spherical aggregates (called β-CD-PEG-G aggregates) that can stably exist in an aqueous solution and entrap doxorubicin (Dox) to form β-CD-PEG-G-Dox nanomedicine. Dox encapsulation efficiency is approximately 79 ± 6.3%. Dox from β-CD-PEG-G-Dox nanomedicine exhibits sustained release and pH responsiveness. Cell and animal experiments showed that β-CD-PEG-G-Dox nanomedicine could effectively induce cancer cell apoptosis to exert antitumor activity. Unexpectively, the animal experiment and tissue sections demonstrated that β-CD-PEG-G aggregates exhibit certain antitumor activity that could delay the tumor growth. Therefore, the β-CD-PEG-G molecule has high potential as a drug carrier candidate.

Construction of a Dual Drug Carrier on the Basis of Hollow Structured Upconversion Nanoparticles for pH‐Responsive Drug Delivery and UCL/MRI Dual Mode Imaging

AbstractA series of Gd3+ doping hollow upconversion nanoparticles NaYF4:Yb,Gd,Tm (h‐UNCP) are prepared successfully. The hollow NaYF4:Yb,Gd,Tm possess excellent upconversion luminescence (UCL) and large longitudinal relativity (r1 = 128.3 mm−1 s−1), which can be potentially used for UCL/magnetic resonance imaging (MRI) dual mode imaging. On the basis of the optimal h‐UCNP, doxorubicin hydrochloride (DOX) and methotrexate (MTX) are used as drug models to prepare a dual drug carrier. After the encapsulation of DOX on the h‐UCNP, chitosan (CS) is further wrapped and then used to load MTX to obtain a dual drug carrier h‐UCNPs/DOX/CS/MTX. The pH responsive release of DOX and MTX is discussed. The MTX release climbs from 33% to 100% by regulating the pH from 5.8 to 7.4. The DOX release is different at different pH conditions. The synergistic effect of DOX and MTX on the cancer cells is confirmed by cell viability. The h‐UCNPs/DOX/CS/MTX are tracked by cells UCL imaging and vivo MRI imaging. The excellent performance of UCL imaging and positive MRI images demonstrates that h‐UCNPs/DOX/CS/MTX can be used for UCL/MRI dual mode imaging. All the results show the potential application of h‐UCNPs/DOX/CS/MTX in pH responsive release and UCL/MRI dual imaging.

Liposome-based codelivery of celecoxib and doxorubicin hydrochloride as a synergistic dual-drug delivery system for enhancing the anticancer effect

Combination therapy with conventional chemotherapeutic drugs strongly demonstrates a good approach to reduce cytotoxicity, resistance, and the dose of the potent anticancer drugs. The purpose of this research was to design and characterize liposome incorporating celecoxib (CEL) and doxorubicin hydrochloride (DOX) and investigate the anti-tumor efficacy of this combination on different tumor cells. A simple comparison study had been performed for liposomes formulation using thin-film hydration method and pH-gradient method. HSPC-incorporated liposomes were chosen for encapsulation of both CEL and DOX. The formulations showed small particle size and polydispersity index with high encapsulation efficiency. DOX/CEL liposomes displayed the strongest cytotoxicity against B16 and MGC80-3 cells in comparison to the corresponding drug solutions. By incorporation of both agents, a significant reduction in IC50 from 0.927 to 0.198 µg/ml and from 0.81 to 0.535 µg/ml against B16 cells and MGC80-3 cells, respectively, was observed. CEL also significantly improved the intracellular retention and accumulation of DOX in vitro. Our data suggest that the developed liposomal formulation proved to be the most effective formulative strategy as a dual drug delivery system for incorporation of both doxorubicin HCL and CEL and could be considered a useful tool for enhancing the therapeutic efficacy of the anticancer drug.

The crucial role of macromolecular engineering, drug encapsulation and dilution on the thermoresponsiveness of UCST diblock copolymer nanoparticles used for hyperthermia

Poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)), an upper critical solution temperature (UCST)-type copolymer in water, was synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization and used as a macro-RAFT agent for the polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) to yield amphiphilic diblock P(AAm-co-AN)-b-POEGMA copolymer. A series of copolymers with different AN content was obtained allowing to finely tune the UCST behavior (cloud point (Tt-UCST) from 35 to 78 °C). Addition of the POEGMA block did not modify the Tt-UCST regardless its Mn but provided a lower critical solution temperature behavior at high temperature. Nanoparticles were then formulated by the nanoprecipitation technique revealing that copolymers with higher Tt-UCST yield smaller, better-defined nanoparticles. Eventually, doxorubicin (Dox) was encapsulated into nanoparticles made from the copolymer having a Tt-UCST close to mild hyperthermia (~43 °C). Surprisingly, Dox encapsulation increased Tt-UCST and gave smaller nanoparticles as opposed to their unloaded counterparts. The dilution of the suspension also led to a decrease of Tt-UCST. No obvious hyperthermia effect was observed on the cytotoxicity of Dox-loaded nanoparticles. Our study highlighted the influence of macromolecular engineering, drug encapsulation and nanoparticle dilution on UCST behavior, important features often overlooked despite their crucial impact in the development of thermosensitive nanoscale drug delivery systems.

The cyclodextrin inclusion complex-containing biodegradable polymeric systems as drug carrier

This article shows that the supramolecular micelle assemblies from PCL-b-P4VP block copolymers with α-CD via self-assembly of inclusion complexes in an aqueous solution. Dox encapsulation and the release at different pH of supramolecular micelle assemblies from poly (ε-caprolactone-block-4-vinylpyridine) (PCL-b-P4VP) block copolymers with α-CD showed excellent cytocompatibility. Dox was successfully loaded into the micelles with a loading content of 14.4% and loading efficiency of 28.9% by using UV-Vis spectroscopy (UV). The Dox loaded micelles showed lower cytotoxicity than free drugs, and could efficiently deliver and release the drug into human hepatocellular carcinoma (Hep-G2) cells as confirmed by confocal laser scanning microscopy (CLSM). These properties make the polymer micelles attractive as drug carriers for pharmaceutical applications.

Effects of Lignin-Based Hollow Nanoparticle Structure on the Loading and Release Behavior of Doxorubicin.

Because of their exceptional absorption capacity, biodegradability, and nontoxicity, nanomaterials fabricated from renewable natural resources have recently become an increasingly important research area. However, the mechanism of drug encapsulation by lignin nanoparticles and the role of nanoparticle structure on the stability and loading performance still remain unknown. Herein, lignin hollow nanoparticles (LHNPs) were prepared and applied as promising vehicles for the antineoplastic antibiotic drug doxorubicin hydrochloride (DOX). The hydrogen bonding and π−π interactions contributed to the encapsulation of hydrophilic DOX by LHNPs with hydrophobic cavities. The encapsulation of DOX was enhanced by the pore volume and surface area. In addition, the nanoparticles contributed to the cellular uptake and the accumulation of the drug within HeLa cells. This work provides a scientific basis for future studies on the selective entrapment properties of hollow polymer nanoparticles derived from biomass material as vehicles for overcoming pharmacokinetic limitations.

In vitro study of BSA gel/polyelectrolite complexes core shell microcapsules encapsulating doxorubicin for antitumoral targeted treatment

The aim of this study is to develop core shell microcapsules of bovine serum albumin (BSA) gel with a complex polyelectrolite multilayer shell of natural polysaccharides with opposite charges, pectin (P), chitosan (Chi), and hyaluronic acid (HA) respectively, encapsulating Doxorubicin (Dox) as a carrier for targeted anti-tumoral treatment of hepatic cell carcinoma (HCC). A sacrificial CaCO3 template method was used in order to obtain microcapsules with a BSA gel core and a layer-by-layer (Lbl) deposition technique of polyelectrolite complexes formed between P/Chi in the inner layers and HA/Chi in the outer shell layers. The preformed microcapsules, BSA gel/P/Chi/HA, noted as ms, have been applied for Dox encapsulation (ms-Dox). Dox encapsulation and release in different pH media were studied in order to elucidate the interactions between pH dependently charged species involved in the Dox loading/releasing processes. The structure characterization of ms/ms-Dox was evaluated by FTIR and UV-Vis spectroscopy, X-ray diffraction, thermal analy sis, optical microscopy, confocal laser scanning microscopy, and scanning electron microscopy. The in vitro study for citotoxicity assessment on normal and tumoral cells of both ms and ms-Dox was performed using mesenchymal stem cells (MSCs) and Hep2G HCC cell lines. Results of physical-chemical analyses confirm the successful encapsulation of Dox in ms, and the in vitro biological study recommends ms-Dox as a candidate for future in vivo research as a targeted anti-tumoral treatment modality applications.