Carrier For Delivery Of Anticancer Drugs Research Articles

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.

Novel biphenylene as cisplatin anticancer drug delivery carrier; insight from theoretical perspective

The delivery of anticancer drugs at target sites is a major challenge. Here we have explored the suitability of biphenylene as a nanocarrier for the anti-cancer drug cisplatin, using density functional theory. Biphenylene can be a promising nanocarrier for the delivery of anticancer drug due to its physical stability, rapid release rate, solubility, and bio-compatibilities compared to other nanocarriers. Cisplatin was placed at different locations of biphenylene and found that the hexa site is the preferred site with adsorption energy of −0.35 eV. The Bader charge and density of states analyses confirms that the surface of biphenylene can absorb cisplatin with a charge transfer from cisplatin to biphenylene. We have verified the aqueous solubility of cisplatin and its dispersion in the human body. Ab initio molecular dynamics have been performed at room temperature to confirm the stability of the drug bound with the nanocarrier. By computing desorption temperature and its pH dependence; we confirm that the drug is released at body temperature in an acidic environment. Moreover the biphenylene exihibited excellent cytotoxicity activity and biological cellular uptake of drug with protein also confirmed through molecular docking. Based on these results, biphenylene can be used as a potential nanocarrier for the cisplatin delivery.

Hydrophobicity-Adaptive Polymers Trigger Fission of Tumor-Cell-Derived Microparticles for Enhanced Anticancer Drug Delivery.

Tumor-cell-derived microparticles (MPs) can function as anticancer drug-delivery carriers. However, short blood circulation time, large-size-induced insufficient tumor accumulation and penetration into tumor parenchyma, as well as limited cellular internalization by tumor cells and cancer stem cells (CSCs), and difficult intracellular drug release restrict the anticancer activity of tumor-cell-derived MP-based drug-delivery systems. In this work, hydrophobicity-adaptive polymers based on poly(N-isopropylacrylamide) are anchored to tumor-cell-derived MPs for enhanced delivery of the anticancer drug doxorubicin (DOX). The polymers are hydrophilic in blood to prolong the circulation time of DOX-loaded MPs (DOX@MPs), while rapidly switching to hydrophobic at the tumor acidic microenvironment. The hydrophobicity of polymers drives the fission of tumor-cell-derived MPs to form small vesicles, facilitating tumor accumulation, deep tumor penetration, and efficient internalization of DOX@MPs into tumor cells and CSCs. Subsequently, the hydrophobicity of polymers in acidic lysosomes further promotes DOX release to nuclei for strong cytotoxicity against tumor cells and CSCs. The work provides a facile and simple strategy for improved anticancer drug delivery of tumor-cell-derived MPs.

Interactions between β-cyclodextrin as a carrier for anti-cancer drug delivery: a molecular dynamics simulation study

A series of molecular dynamics simulations were performed on 5-fluorouracil (5-Fu), Alendronate (Ald), and Temozolomide (TMZ) anticancer drugs in the presence and absence of β-cyclodextrin (βCD) as a carrier. Thermodynamic investigations showed that the van der Waals interaction energy was dominant in loading all drugs inside the βCD cavity. The sum of the interaction energies illustrated that the highest affinity was related to Ald (−136.5 kJ/mol), which in turn was due to the presence of bulky and charged atoms of phosphorus and oxygen, although TMZ (−115.92 kJ/mol) showed a very high affinity as well. At the same time, the hydrogen bond analysis also represented that Ald had the most hydrogen bond (1.97) with the highest half-life (3.13 ps) with βCD. Investigation of the root mean fluctuation (RMSF) indicated that all the drugs had a relatively rigid structure and maintain this rigidity during loading in the βCD cavity, and in the meantime, Ald was slightly more flexible than 5-Fu and TMZ. The area of ​the primary hydroxyl rim decreased in all drug-containing systems, which in turn was caused by the attractive interaction of drugs with oxygens in the primary hydroxyl rim. Especially for those drugs that were able to penetrate to the end of the primary hydroxyl rim of the βCD, that means TMZ and 5-Fu. Meanwhile, due to the lack of Ald penetration to the end of the primary hydroxyl rim, the area change in the Ald-containing system was less than in the two others. Communicated by Ramaswamy H. Sarma

Acid/reduction dual-sensitive amphiphilic graft polyurethane with folic acid and detachable poly(ethylene glycol) as anticancer drug delivery carrier

In order to not only improve the stability of nanomicelles in blood circulation but also promote the cellular uptake in tumors and rapidly release the encapsulated drugs in tumor cells, a kind of acid/reduction dual-sensitive amphiphilic graft polyurethane with folic acid and detachable poly(ethylene glycol) (FA-PUSS-gimi-mPEG) was synthesized by grafting folic acid and monomethoxy poly(ethylene glycol) to the polyurethane side chain. FA-PUSS-gimi-mPEG could self-assemble in aqueous solution to form negatively charged nanomicelles, which endowed them good stability under normal physiological condition. Using ultraviolet-visible spectrometer (UV–vis) and dynamic light scattering (DLS), it was found that the hydrophilic poly(ethylene glycol) layer of FA-PUSS-gimi-mPEG micelles could be detached due to the cleavage of benzoic-imine bond under slightly acidic condition, which resulted in reversing the charge of the micellar surface and exposing folic acid to the micellar surface. FA-PUSS-gimi-mPEG micelles could load doxorubicin (DOX), moreover the drug release rate was faster at pH 5.0 and 10 mM glutathione (GSH) than that under normal physiological condition. The results of cell experiments further demonstrated that FA-PUSS-gimi-mPEG micelles had acid/reduction dual-sensitive property. The changes in the structure of FA-PUSS-gimi-mPEG micelles could enhance the cellular uptake under acid condition and the micelles could accelerate the drug release in tumor cells due to the presence of disulfide bonds in the polymer. Therefore, FA-PUSS-gimi-mPEG micelles could efficiently deliver anticancer drug into tumor cells and enhance the inhibition of cellular proliferation through multi-effect synergy.

Synthesis and Evaluation of Multi Layered Magnetic Nanoparticles as Versatile Carrier for Anti-Cancer Drug Delivery

The objective of this study is to develop a passive targeting of multilayered nanoparticles encountering multiple obstacles on the way to their target due to the mucosal barrier, nonspecific uptake of the drug. To prevent the nonspecific drug toxicity and combination chemotherapy for synergistic effect, multifunctional ferromagnetic properties were successfully fabricated by the layer-by-layer assembly (LBL) technique. The drug-loaded magnetic chitosan nanospheres were coated alternatively with sodium alginate and chitosan up to 3 layers incorporated with melphalan and methotrexate. The core-shell type composites consisting of magnetic nanoparticles decorated with biological substances are interesting for various biomedical applications. The magnetic property investigation reveals that drug-loaded nanomaterials exhibit superparamagnetic behavior. The uniformly distributed magnetic nanoparticles were also observed in scanning electron microscopic images to characterize the synthesized product. The thin film consisting of chitosan nanospheres was coated alternatively with sodium alginate and magnetic nanoparticles had a conductivity of two formulations F1a and F2a were 35.2 emu/g and 43.4 emu/g respectively. The formulation was evaluated for its particle size, size distribution, zeta potential, and in-vitro drug release in the pH of 1.2 and 7.0 fitted in kinetic release studies. The developed magnetic nanoparticles showed promising results with better- delayed drug action and will be an enhanced therapeutic means in combating the infections of cancer therapy.

Antibacterial metal-phenolic nanosheets as smart carriers for the controlled release of epirubicin hydrochloride.

Bacterial infections can cause serious complications in cancer treatment and have been proven to weaken therapeutic benefits. Recently, antibacterial nanomaterials that serve as carriers for anticancer drug delivery have been attracting extensive interest due to their combined antimicrobial and anticancer activities. In this study, antibacterial metal-phenolic nanosheets (Cu-TA) were successfully prepared via the self-assembly of the metal-phenolic coordination complexes formed between copper ions and tannic acid, and the structure, morphology, and formation mechanism of Cu-TA nanosheets were explored. The antibacterial activity of Cu-TA nanosheets against both Gram-positive and Gram-negative bacteria was detected using the minimum inhibitory concentration (MIC), zone of inhibition and plate counting methods. The MIC values of both bacterial strains were about 0.4 mg mL-1, and the killing rates of Cu-TA samples were close to 100% at the concentration of 2 and 0.2 mg mL-1 after 12-hour incubation. Epirubicin hydrochloride (EPI) molecules were successfully loaded on the porous Cu-TA nanosheets mainly through the formation of the Cu-EPI chelate complex and strong electrostatic interactions. The Cu-EPI complex and Cu-TA nanosheets could be disassembled under acidic conditions or in the presence of high levels of glutathione (GSH) after uptake by cancer cells, which triggered the unique pH and GSH-responsive controlled release behaviors of EPI and copper ions. The MTT assay results revealed that the presence of bacteria in Hep G2 cells can greatly impair the cell death rate induced by free EPI, but the resultant EPI-loaded Cu-TA nanosheets can significantly enhance cell death both in the presence and absence of bacteria.

Hydrophobic modified poly(l‐glutamic acid) graft copolymer micelles with ultrahigh drug loading capacity for anticancer drug delivery

AbstractSelf‐assembled polymeric nanoparticle (NP) drug carriers are capable of encapsulated and controlled delivery, facilitating improvements in the therapeutic efficiency of drugs. Here we report a series of poly(l‐glutamic acid)‐g‐methoxy poly(ethylene glycol)/4‐phenylbutyl ester (PLG‐g‐mPEG/PB) copolymers, which were synthesized by esterification of 4‐phenylbutanol (PB) and PLG‐g‐mPEG in different feed ratios. The copolymers obtained form into nano‐sized micelles in aqueous solution by a self‐assembly process, with lower critical micelle concentration value for higher PB ratio in the copolymers. Variable temperature infrared spectroscopy and circular dichroism were used to prove the breaking of intermolecular hydrogen bonds after PB modification. Podophyllotoxin (PPT), an effective anticancer agent, was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interaction between the drug and the PB‐modified copolymers. Both the drug loading content and the loading efficiency increased with PB content in the PLG‐g‐mPEG/PB copolymers and reached an ultrahigh value of 28.2 wt% and 94%, respectively. The PPT‐encapsulated micelles (PPT‐NPs) were stable at pH 7.4 but dissociated and released 80% of loaded PPT in a weak acidic environment (pH 5.0). The in vitro proliferation of non‐small‐cell lung cancer cells (A549) was significantly inhibited by PPT‐NPs in a cytotoxicity assay. These results demonstrate that hydrophobic modification is an efficient route for tuning the self‐assembly behaviour and drug encapsulation of PLG‐g‐mPEG copolymers, and our PLG‐g‐mPEG/PB will serve as a promising carrier for hydrophobic anticancer drug delivery. © 2021 Society of Industrial Chemistry.

CeO2 nanoparticles incorporated MIL-100(Fe) composites for loading of an anticancer drug: Effects of HF in composite synthesis and drug loading capacity

In recent years, a lot of effort has gone into developing metal organic frameworks (MOFs) based composites as anticancer drug delivery carriers. Among them, various nanoparticles (NPs) such as graphene oxide (GO), Iron oxide (Fe3O4 or Fe2O3), zinc oxide has been utilized to impart additional benefits in MOFS structure. In this study, CeO2 particles and its composites with MIL-100(Fe) were studied for loading and subsequent release of the anticancer medication doxorubicin hydrochloride (DOX). The pure MIL-100(Fe) and CeO2@ MIL-100(Fe) composites were synthesised using two different methods: a traditional HF route (HF acts as a crystallising agent) and another without HF. It was found that during the composite synthesis, CeO2 was transformed to CeF3 in the presence of HF. The MOF-composites that resulted had a lower DOX loading capacity than pure CeO2 but were quite equivalent to pure MOF. However, in absence of HF, such transformation of CeO2 was not occurred in the composites. All the composites have a regulated DOX release pattern as compare to the undesirable burst release characteristics of pure CeO2.

Bioactive Polysaccharides Based Graphene Oxide Nanoparticle as a Promising Carrier for Anticancer Drug Delivery

Nowadays, the concept of drug transmission is a prominent issue in the world of drug delivery research. We investigated the development of a hybrid platform based on graphene oxide/chitosan and xyloglucan (GO-CH-Xn) for the loading and release of doxorubicin (DOX)., where chitosan (CS) natural polymer functionalizes graphene oxide and is then grafted by xyloglucan (Xn) natural hydrophilic polysaccharide to form a reliable nanocarrier system for the delivery of DOX. UV-Vis spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Raman spectroscopy, transmission electron microscopy, and scanning electron microscopy analysis were used to confirm the fundamental physicochemical properties. The DOX loading capacity and efficiency were 81.8% and 73.5%. The graphene oxide-chitosan-xyloglucan- doxorubicin (GO-CS-Xn-DOX) drug delivery system showed a pH-regulated release as observed by UV analysis. Biocompatibility was evaluated via in vitro hemolysis assay, indicates negligible toxicity, and the anticancer activity of the developed nanocarrier system was studied by 3-(4, 5-dimethylthiazol-2-Y)-2,5-diphenyltetrazolium bromide (MTT) against human (U 87) glioblastoma cancer cell lines. The in vitro studies demonstrate the major advantages of the developed approach by demonstrating its capability as a promising nanocarrier for biomedical applications.

Preparation and in-vitro evaluation of mesoporous biogenic silica nanoparticles obtained from rice and wheat husk as a biocompatible carrier for anti-cancer drug delivery

In this study, mesoporous silica nanocarriers were synthesized from natural sources such as rice and wheat husk for drug delivery application. First, the biogenic silica in cereals husk was extracted by acid leaching and then converted to sodium silicate as a silica precursor. Mesoporous silica nanoparticles were then synthesized by adding sodium silicate to the template mixture by continuous and discrete modes during the sol-gel process. The effects of natural sources type and precursor addition method on nanocarriers‘ morphological and physicochemical properties were investigated by XRD, FT-IR, BET and SEM analysis. Our results showed rice husk-based spherical nanocarriers were more crystalline with slit-shaped pores, while wheat husk-based nanocarriers had been composed of spherical nanoparticles with narrow cylindrical pores. The results also showed that by adding the precursor discretely, their hydrophilicity, particle size and pore size increased compared with the continuous mode, probably due to the high initial concentration of the precursor in the reaction mixture. Doxorubicin (Dox), as a model anticancer drug was loaded into the nanocarriers, and the drug release behavior was studied at two different pH values (7.4 and 5.4). In general, the accumulated released drug at pH 5.4 was approximately twice as much as pH 7.4 due to the higher solubility of doxorubicin at acidic environment. Also, the accumulated released drug at pH 5.4 for nanocarriers which had been synthesized by discrete mode, was higher than continuous mode, due to the larger pore diameter of them. The biocompatibility and cytotoxicity of nanocarriers and Dox-loaded nanocarriers were also investigated on the HFF-2 and MCF-7 cell lines, respectively. Moreover, apoptosis, as the mechanism of cell death, was evaluated by morphological study of the MCF-7 cells. Within acceptable toxicity limits and apoptosis induction, the Dox-loaded nanocarriers, especially discrete mode synthesized nanocarriers, exhibited high-efficiency anticancer effect on the MCF-7 cell line.

Conjugation of a smart polymer to doxorubicin through a pH-responsive bond for targeted drug delivery and improving drug loading on graphene oxide.

Polymeric nanoparticles have emerged as efficient carriers for anticancer drug delivery because they can improve the solubility of hydrophobic drugs and also can increase the bio-distribution of drugs throughout the bloodstream. In this work, a computational study is performed on a set of new pH-sensitive polymer–drug compounds based on an intelligent polymer called poly(β-malic acid) (PMLA). The molecular dynamics (MD) simulation is used to explore the adsorption and dynamic properties of PMLA–doxorubicin (PMLA–DOX) interaction with the graphene oxide (GOX) surface in acidic and neutral environments. The PMLA is bonded to DOX through an amide bond (PMLA-ami-DOX) and a hydrazone bond (PMLA-hz-DOX) and their adsorption behavior is compared with free DOX. Our results confirm that the polymer–drug prodrug shows unique properties. Analysis of the adsorption behavior reveals that this process is spontaneous and the most stable complex with a binding energy of −1210.262 kJ mol−1 is the GOX/PMLA-hz-DOX complex at normal pH. On the other hand, this system has a great sensitivity to pH so that in an acidic environment, its interaction with GOX became weaker while such behavior is not observed for the PMLA-ami-DOX complex. The results obtained from this study provide accurate information about the interaction of the polymer–drug compounds and nanocarriers at the atomic level, which can be useful in the design of smart drug delivery systems.

Polycaprolactone–Gelatin Membranes in Controlled Drug Delivery of 5-Fluorouracil

Nanofibers are known as promising carriers for anticancer drug delivery, particularly in postoperative local chemotherapy, through surgical grafting the membrane. In this study, blends of poly (e‑caprolactone) (PCL) and gelatin (Ge) at various polymeric proportions were used for electrospinning of the nanofibers containing the anticancer drug of 5-Fluorouracil (5-FU). The electrospinning was performed at three different conditions to study the influence of processing parameters on the membrane properties. The morphology and tensile properties of the PCL-Ge nanofibers were reliant on the gelatin ratio and the processing condition. Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) outcomes demonstrated that 5-Fluorouracil (5-FU) was well distributed in the fiber matrix, forming H-bonds and in an amorphous state. Weight loss measurements and drug release study showed much faster degradation, and 5-FU releasing from the nanofibers contained a higher amount of gelatin. Studying the cytotoxicity of the 5-FU-loaded nanofibers showed that the P70G30FU had well restrained the survive, attachment, and proliferation of HT-29 colorectal cancer cells. Therefore, the 5-FU loaded PCL-Ge nanofibers have the ability of controlled drug release following the desired cancer treatment protocol.

Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics.

The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via; the loading of various anticancer agents. Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via; the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

Development of ROS-responsive amino acid-based poly(ester amide) nanoparticle for anticancer drug delivery.

Reactive oxygen species (ROS) play an important role in cellular metabolism and many oxidative stress related diseases. Oxidative stress results from toxic effects of ROS and plays a critical role in the pathogenesis of a variety of diseases like cancers and many important biological processes. It is known that the unique feature of high intracellular ROS level in cancer cells can be considered as target and utilized as a useful cancer-related stimulus to mediate intracellular drug delivery. Therefore, biomaterials responsive to excess level of ROS are of great importance in biomedical applications. In this study, a novel ROS-responsive polymer based on L-methionine poly(ester amide) (Met-PEA-PEG) was designed, synthesized, characterized and self-assembled into nano-micellar-type nanoparticles (NP). The Met-PEA-PEG NP exhibited responsiveness to an oxidative environment. The size and morphology of the nanoparticle changed rapidly in the presence of H2 O2 . The Nile Red dye was loaded into the Met-PEA-PEG NP to demonstrate a H2 O2 concentration induced time-dependent release behavior. The Met-PEA-PEG NP was sensitive to high intracellular ROS level of PC3 prostate cancer cells. Furthermore, the Met-PEA-PEG NP was investigated as a carrier of a Chinese medicine-based anticancer component, gambogic acid (GA). Compared to free GA, the GA-loaded nanocomplex (GA-NP) showed enhanced cytotoxicity toward PC3 and HeLa cells. The GA-NP also induced a higher level of apoptosis and mitochondrial depolarization in PC3 cells than free GA. The Met-PEA-PEG NP improved the therapeutic effect of GA and may serve as a potential carrier for anticancer drug delivery.

Zwitterionic Unimolecular Micelles with pH and Temperature Response: Enhanced In Vivo Circulation Stability and Tumor Therapeutic Efficiency.

Circulation stability in vivo and stimuli-responsiveness under a tumor microenvironment of the polymeric prodrug micellar drug delivery systems are very critical to improve the tumor therapeutic efficiency. In this study, a series of polyamidoamine (PAMAM)-graft-poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA)-block-poly(betaine sulfonate) (PSBMA) (PDS) unimolecular micelles were prepared via atom transfer radical polymerization. PAMAM served as a hydrophobic core to load the drug, the PDMAEMA segment was a middle layer to provide both thermo- and pH-sensitivity, whereas the PSMBA shell layer was used to improve the stability of the unimolecular micelles. The PDS exhibited a spherical structure with the size of 10-20 nm at pH 7.4. PDS micelles had excellent stability to resist the large volume liquid dilution. Moreover, it exhibited excellent stability in a complex biological microenvironment because of a superhigh antiprotein adhesion capacity of the PSBMA shell layer compared with PAMAM micelles. Drug release studies confirmed that the DOX can remain in the PDS micelles at pH 7.4 and 37 °C, whereas it can rapidly be released when the pH decreases to 5.0 and/or the temperature increases to 40 °C. In vitro studies suggested that the PDS drug delivery system can effectivity induce apoptosis and inhibit the proliferation of cancer cells. In vivo studies suggested that the PDS micelles prolonged the circulation time, decreased the side effects, and increased the antitumor efficacy. Therefore, the prepared PDS micelles are a potential anticancer drug delivery carrier for cancer therapy.

Boron nitride nanocluster as a carrier for lomustine anticancer drug delivery: DFT and thermodynamics studies

Previous reports were shown that boron nitride nanostructures can be biocompatible and nontoxic. Therefore, interaction of lomustine as an anticancer drug with B12N12, B24N24, and Ga- and Al-doped B24N24 was investigated using density functional theory (DFT) to explore a new drug delivery system. All calculations were investigated by the B3PW91 method and 6-311G(d,p) basis set. It has been demonstrated that the interaction of lomustine with Ga- and Al-doped B24N24 is more stable than pure B12N12 and B24N24. Despite both Ga- and Al-doped B24N24 provide more negative adsorption energy, the electronic properties’ calculation was indicated Al-doped B24N24 sensitive to the drug adsorption. It is predicted that lomustine drug incorporating Al-doped B24N24 can be extended as a drug delivery system.

Fabrication of Mixed Polymeric Micelles Based on Stimuli-Responsive Amphiphilic Copolymers for Drug Delivery and Controlled Release

In this report, mixed polymeric micelles (MPMs) system self-assembled from two kinds of cholesterol-grafted amphiphilic block copolymers cholesterol modified poly ([Formula: see text]-amino esters)-grafted disulfide poly (ethylene glycol) methyl ether (PAE(-ss-mPEG)-[Formula: see text]-Chol) and poly([Formula: see text]-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-[Formula: see text]-mPEG-Chol) were prepared for drug delivery and controlled release with pH and redox-responsibilities. The self-assembly of two block copolymers was evaluated by measurement of critical micelle concentration (CMC) values using fluorescence spectroscopy. The hydrodynamic diameter, polydispersity index (PDI) and zeta-potential of MPMs in aqueous were recorded by dynamic light scattering (DLS) at different conditions. Doxorubicin (DOX) was efficiently encapsulated in the micellar core by the hydrophobic interaction. The drug loading content (LC) and encapsulation efficacy (EE) of MPMs with different formulations were evaluated. The DOX was released due to the swelling and disassembly of MPMs induced by low pH and high glutathione (GSH) concentrations. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values and reducing agents. The results showed that the MPMs could be the potential anticancer drug delivery carriers with pH/redox-triggered drug release profile.

Antitumor efficacy and cardiotoxic effect of doxorubicin-loaded mixed micelles in 4T1 murine breast cancer model. Comparative studies using Doxil® and free doxorubicin

Doxorubicin-loaded mixed micelles (DOX-micelles) were formulated employing TPGS and a poloxamine (Tetronic® T1107) in order to investigate their pharmaceutical application as an alternative anticancer nanotherapy. DOX-micelles presented unimodal behaviour, exhibiting average size values of 10.7 ± 0.2 nm and 10.4 ± 0.1 nm, before and after lyophilization, respectively. The in vitro cytotoxic effect of DOX-micelles was significantly higher (p < 0.05) than Doxil® on 4T1 murine breast cancer cells. The in vitro cell-based internalization assays showed a significant augment (p < 0.05) of the intracellular DOX content for the DOX-micelles in comparison to the liposomes and free DOX in these 4T1 cells at 2 and 6 h. Besides, DOX-micelles presented higher in vivo anticancer effect than Doxil® and equivalent potency to the free drug. Moreover, the in vivo histopathological toxicity studies revealed that the DOX-micelles produced significant less cardiac damage than free DOX, while the in vivo immunohistochemical assays exhibited a significantly higher DNA damage in the cardiac tissue with the free DOX than with our DOX-micelles. All these results demonstrate that our novel nanotechnological platform could successfully deliver DOX to the tumor with reduced cardiotoxicity, thus showing promising clinical potential as an anticancer drug delivery carrier.

Layer-by-layer pH-sensitive nanoparticles for drug delivery and controlled release with improved therapeutic efficacy in vivo

In this work, a pH-sensitive liposome–polymer nanoparticle (NP) composed of lipid, hyaluronic acid (HA) and poly(β-amino ester) (PBAE) was prepared using layer-by-layer (LbL) method for doxorubicin (DOX) targeted delivery and controlled release to enhance the cancer treatment efficacy. The NP with pH-sensitivity and targeting effect was successfully prepared by validation of charge reversal and increase of hydrodynamic diameter after each deposition of functional layer. We further showed the DOX-loaded NP had higher drug loading capacity, suitable particle size, spherical morphology, good uniformity, and high serum stability for drug delivery. We confirmed that the drug release profile was triggered by low pH with sustained release manner in vitro. Confocal microscopy research demonstrated that the NP was able to effectively target and deliver DOX into human non-small cell lung carcinoma (A549) cells in comparison to free DOX. Moreover, the blank NP showed negligible cytotoxicity, and the DOX-loaded NP could efficiently induce the apoptosis of A549 cells as well as free DOX. Notably, in vivo experiment results showed that the DOX-loaded NPs effectively inhibited the growth of tumor, enhanced the survival of tumor-bearing mice and improved the therapeutic efficacy with reduced side-effect comparing with free drug. Therefore, the NP could be a potential intelligent anticancer drug delivery carrier for cancer chemotherapy, and the LbL method might be a useful strategy to prepare multi-functional platform for drug delivery.