Anticancer Drug Delivery System Research Articles

Polysaccharide-Drug Conjugates: A Tool for Enhanced Cancer Therapy.

Cancer is one of the most widespread deadly diseases, following cardiovascular disease, worldwide. Chemotherapy is widely used in combination with surgery, hormone and radiation therapy to treat various cancers. However, chemotherapeutic drugs can cause severe side effects due to non-specific targeting, poor bioavailability, low therapeutic indices, and high dose requirements. Several drug carriers successfully overcome these issues and deliver drugs to the desired sites, reducing the side effects. Among various drug delivery systems, polysaccharide-based carriers that target only the cancer cells have been developed to overcome the toxicity of chemotherapeutics. Polysaccharides are non-toxic, biodegradable, hydrophilic biopolymers that can be easily modified chemically to improve the bioavailability and stability for delivering therapeutics into cancer tissues. Different polysaccharides, such as chitosan, alginates, cyclodextrin, pullulan, hyaluronic acid, dextran, guar gum, pectin, and cellulose, have been used in anti-cancer drug delivery systems. This review highlights the recent progress made in polysaccharides-based drug carriers in anti-cancer therapy.

Impact of ErbB Receptors and Anticancer Drugs against Breast Cancer: A Review.

Human EGFR (epidermal growth factor receptor) family of tyrosine kinase receptors consists of four members, ErbB1-4. Abnormalities in the ErbB family characterize a variety of human cancers, including breast cancer. Tyrosine kinase is recruited by the activated EGFR cell surface receptor, which transmitted signals from the receptor to interact with intracellular signaling pathways and regulate cellular functions and biological processes. Targeting the intracellular signaling pathways has been aided in the drug development that was already in use and more continually being developed. The review article highlights the function of ErbB receptors/ligands, their role in signaling pathways, effective targeted drugs, and a combination of targeted drug strategies in the treatment of breast cancer that could be leading to the novel combination of anticancer drug delivery systems.

Folic Acid-Adorned Curcumin-Loaded Iron Oxide Nanoparticles for Cervical Cancer.

Cancer is a deadly disease that has long plagued humans and has become more prevalent in recent years. The common treatment modalities for this disease have always faced many problems and complications, and this has led to the discovery of strategies for cancer diagnosis and treatment. The use of magnetic nanoparticles in the past two decades has had a significant impact on this. One of the objectives of the present study is to introduce the special properties of these nanoparticles and how they are structured to load and transport drugs to tumors. In this study, iron oxide (Fe3O4) nanoparticles with 6 nm sizes were coated with hyperbranched polyglycerol (HPG) and folic acid (FA). The functionalized nanoparticles (10–20 nm) were less likely to aggregate compared to non-functionalized nanoparticles. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles were compared in drug loading procedures with curcumin. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles’ maximal drug-loading capacities were determined to be 82 and 88%, respectively. HeLa cells and mouse L929 fibroblasts treated with nanoparticles took up more FA@HPG@Fe3O4 nanoparticles than HPG@Fe3O4 nanoparticles. The FA@HPG@Fe3O4 nanoparticles produced in the current investigation have potential as anticancer drug delivery systems. For the purpose of diagnosis, incubation of HeLa cells with nanoparticles decreased MRI signal enhancement’s percentage and the largest alteration was observed after incubation with FA@HPG@Fe3O4 nanoparticles.

Guar gum-g-poly(N-acryloyl-L-phenyl alanine) based pH responsive smart hydrogels for in-vitro anticancer drug delivery

ABSTRACT In this study, modified natural polymeric-based pH-responsive hydrogels (GNAHs) were formulated using guar gum-grafted-poly(N-acryloyl phenyl alanine), 2-hydroxy ethyl acrylate, and 2-acrylamido-2-methyl-1-propane sulfonic acid. GNAH hydrogels were synthesized using a single-step radical polymerization reaction using N,N’-methylenebisacrylamide as a crosslinker and potassium persulfate as an initiator. The GNAH was used for the controlled release of Imatinib mesylate (IMS), an anticancer drug. The FTIR spectroscopy confirmed the IMS loading as well as grafting reaction between GG-g-PNPA and PHEA-co-PAMPS. This was further confirmed by XRD and DSC studies. The IMS also reduced the negative surface charge of the GNAH hydrogel. The microscopic images showed that the GNAH hydrogels have porous and canal structures with IMS molecules entrapped within the pores. The mode of drug release mechanism was assessed by applying various kinetic equations (non-Fickian diffusion mechanism, Higuchi square root and Korsmeyer–Peppas kinetic models) that showed pH-dependent drug release of hydrogels exhibiting an excellent controlled-release pattern for IMS for more than 48 h. Based on the drug release behavior of the as-synthesized amino acid-functionalized hydrogel, it can be suggested that GNAH hydrogels could also be used as a potential pH-responsive anticancer drug delivery system for other anticancer drugs.

Formulation and Characterisation of RGD-FBG Based Nanoscaffolds as Novel Anti-Cancer Drug Delivery System

Aims/Objective: To formulate and evaluate RGD sequenced fibrin/fibrinogen based nanoscaffolds (acid-labile linker) for the treatment of brain tumor targeting to achieve an acid-triggered drug release under a mild acidic condition in tumor.
 Place and Duration of Study: Department of Pharmaceutics, Parul Institute of Pharmacy and Research, Parul University, Vadodara, between 2017 to 2021.
 Methodology: Nanoscaffolds was prepared with Drug–linker–Fbg conjugate solution, using modified water-in-oil (W/O) emulsification/solvent extraction method. The conjugate solution was constantly injected in soya lecithin (100 ml) using a syringe (1 ml/min) and stirred using Magnetic stirrer for 30 minutes to form stable a W/O emulsion. The present investigation was aimed to evaluate with Particle size, Zeta potential measurement, Percent drug entrapment, Transmission electron microscopy.
 Results: As per Evaluation parameters were performed such as Particle size measured as 151.8±2.02 nm to 157.4 ± 3.81 nm. Zeta Potential was found that -37.1±6.32, Percent Drug Entrapment was 91.4±0.37 which indicates that the drug release of lyophilised FBG based nanoscaffolds was indicatively higher as compared to FBG based nanoscaffolds (alone).
 Conclusion: As per the study design the formulated nanoscaffolds were found to impart the drug release based on their particle size and percent drug entrapment and hence fights against cancer cells in brain by their EDC-NHS chemistry. Drug of choice Everolimus along with Fbg based nanoscaffolds offers better biocompatibility by exposing dual responsiveness at acidic environment in tumors. The results of in-vitro drug release reveals the better uptake of drug at targeted site of action.

Synthesis and controlled drug release behavior of micro-mesoporous wollastonite nanoparticles. Effect of calcination temperature on the structural and biodegradability properties

In this study, amorphous and crystalline (Pseudowollastonite) phases of wollastonite (CaSiO3) nanoparticles were successfully synthesized by a facile soft-template method with a micro-mesoporous structure. In addition, the effect of calcination temperature on the structural properties, surface charge, and biodegradability of synthesized nanoparticles were investigated. After that, the drug loading capacity and drug release behavior of the sample calcined at the lowest calcination temperature (600 °C, MMW-600) was investigated with Epirubicin (EPI) as an anti-cancer drug. Noticeably, MMW-600 showed the most appropriate (bio) properties as a candidate of drug carrier in comparison with the samples that calcined at higher temperatures by showing: the least hydrodynamic size (85 nm), the highest specific surface area (301.68 m2g) as well as micro-and mesopore volumes as 0.075 and 0.282 cm3g, respectively. Moreover, it indicated the lowest thickness of the pore wall (6.73 nm) and the highest rate of biodegradation in Tris-HCl. The investigation of drug release behavior revealed a pH-controlled release due to the pH-dependent surface charge of micro-mesoporous wollastonite (MMW) nanoparticles, which was demonstrated by Zeta potential analysis. Additionally, MMW nanoparticles demonstrated a desired high rate and sustained release of EPI (44% and 80% after 4 and 70 h, respectively) in succinate buffer (pH 5.5, mimic the pH of a tumor site). In conclusion, MMW can be a great candidate as a pH-controlled release drug-nanocarrier for anti-cancer drug delivery systems.

Dual responsive tamarind gum-co-poly(N-isopropyl acrylamide-co-ethylene glycol vinyl ether) hydrogel: A promising device for colon specific anti-cancer drug delivery

In this study, pH and temperature-sensitive tamarind gum (TM)-based hydrogels were synthesized by free radical polymerization using a combination of acrylamide (AM), N-isopropyl acrylamide (NIPAM), and ethylene glycol vinyl ether (EGVE) monomers with bis (2-(methacryloyloxy) ethyl phosphate (BMEP) as a crosslinker (TANEB hydrogel). The prepared TANEB hydrogels were characterized by Fourier transform infrared spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy to confirm the formation of functional group interactions and morphology. 5-Fluorouracil (5-FU) as a model drug was loaded into the TANEB hydrogels. Differential thermal calorimetry and XRD confirmed the molecularly loaded 5-FU into TANEB hydrogels. Swelling studies revealed the dual responsive nature of the TANEB hydrogels. An in vitro drug release study was performed at pH 1.2 and 7.4 and at 25 and 37 °C. The release time of 5-FU from the hydrogels was extended up to 12 h. Also, 5FU encapsulated hydrogels showed remarkable cytotoxicity against human colorectal adenocarcinoma cancer cells (HCT116 cells) along with good cell cycle ability. Thus, the TANEB hydrogel formulations could be used as potential delivery system for anticancer drugs.

Magnetic ZnO/CdO Nanocomposite for Effective Drug Delivery System for Cancer Therapy

ZnO, ZnO/CdO, and Magnetic Ni-ZnO/CdO nanocomposite have been eco-friendly synthesized using Black Rice Husk Extract (BRHE) and water instead of hazardous chemicals and solvents. The anticancer drug Doxorubicin (Dox) was loaded on the PVA-coated biomimetic nanomaterials. The successful synthesis of the pure nanomaterials and the Dox-nanomaterial systems has been confirmed by evaluating their structural, crystalline, textural, surface, and optical properties using various characterization techniques. The Dox-nanomaterials systems were used as anticancer drugs against HEPG2 cells as a model of human cancerous cells. The in vitro Dox release was slower and more sustained from Ni-ZnO/CdO composite compared to the other individual nanomaterials, suggesting that a hydrogen bond strongly attached more Dox molecules to the surface Ni-ZnO/CdO. Moreover, the cytotoxicity investigations on the HEPG2 cell line showed that higher toxicity was obtained by Ni-doped nanocomposite, consistent with the results of in vitro release. This study provides novel magnetic Nanocarriers that can be used as anticancer drug delivery systems after more in vivo investigations on animals or clinical investigations.

Bioinspired quantum dots for cancer therapy: A mini-review

The global burden of cancer increases with the passing year and is becoming the primary cause of death globally. Chemotherapy plays an important role but produces side effects, natural compounds seem to be an option with fewer side effects, but their bioavailability remains a concern. Bioinspired Quantum dots (QDs) from plant sources show promising drug delivery and anti-cancer potential with low toxicity. QDs are well known for their optical activity and find their use in various applications and can be used explicitly for bio-imaging and drug delivery in cancer therapy. Further, bioinspired QDs as an anti-cancer drug delivery system is less explored. Thus, this featured article aims to conclude the recent advances in the use of bioinspired QDs for drug delivery in cancer therapy.

Fabrication of cellulose nanocrystals as potential anticancer drug delivery systems for colorectal cancer treatment

Polysaccharide nanocrystals have great potential to be used as improved drug carriers due to their low cost, high biodegradability, and biocompatibility. This study reports the synthesis of cellulose nanocrystals (CNC) loaded with 5-fluorouracil (CNC/5FU) to evaluate their anticancer activity against colorectal cancer cells. X-ray and Fourier-transform infrared spectroscopy demonstrated that acid hydrolysis successfully degraded the amorphous cellulose to liberate the crystal regions. From transmission electron microscopy, CNC/5FU appeared as rod-like nanocrystals with an average length and width of 69.53 ± 1.14 nm and 8.13 ± 0.72 nm, respectively. The anticancer drug 5FU showed improved thermal stability after being loading onto CNC. From UV–vis spectroscopy data, the drug encapsulation efficiency in CNC/5FU was estimated to be 83.50 ± 1.52%. The drug release of CNC/5FU was higher at pH 7.4 compared to those at pH 4.2 and 1.2. From the cytotoxicity assays, CNC did not affect the viability of CCD112 colon normal cells. On the other hand, CNC/5FU exhibited anticancer effects against HCT116 and HT-29 colorectal cancer cells. The anticancer actions of CNC/5FU against HCT116 cells were then confirmed using an in vitro tumor-on-chip model and clonogenic assay. Mechanistic studies demonstrated that CNC/5FU killed the cancer cells by mainly inducing cell apoptosis and mitochondrial membrane damage. Overall, this study indicated that CNC/5FU could be a potential nanoformulation for improved drug delivery and colorectal cancer treatment.

Highly-fluorescent BODIPY-functionalised metallacages as drug delivery systems: synthesis, characterisation and cellular accumulation studies.

With the aim of designing new metallosupramolecular architectures for drug delivery, research has focused on porous 3-dimensional (3D)-metallacages able to encapsulate cytotoxic agents protecting them from metabolism while targeting them to cancer sites. Here, two self-assembled [Pd2L4]4+ cages (CG1 and CG2) featuring 3,5-bis(3-ethynylpyridine)phenyl ligands (L) exo-functionalised with dipyrromethene (BODIPY) groups have been synthesised and characterised by different methods, including NMR spectroscopy and mass spectrometry. 1H NMR spectroscopy studies shows that the cages are able to encapsulate the anticancer drug cisplatin in their hydrophobic cavity, as evidenced by electrostatic potential (ESP) analysis based on XRD studies. The stability of the cages in an aqueous environment, and in the presence of the intracellular reducing agent glutathione, has been confirmed by UV-visible absorption spectroscopy. The luminescence properties of the cages enabled the investigation of their cellular uptake and intracellular localisation in human cancer cells by confocal laser scanning microscopy. In melanoma A375 cells, cage CG1 is taken up via active transport and endocytic trafficking studies show little evidence of transport through the early endosome while the cages accumulated in melanosomes rather than lysosomes. The antiproliferative activity of the lead cage was investigated in A375 together with two breast cancer cell lines, SK-BR-3 and MCF7. While the cage per se is non-cytotoxic, very different antiproliferative effects with respect to free cisplatin were evidenced for the [(cisplatin)2⊂CG1·BF4] complex in the various cell lines, which correlate with its different intracellular localisation profiles. The obtained preliminary results provide a new hypothesis on how the subcellular localisation of the cage affects the cisplatin intracellular release.

Bioorthogonal catalytic nanozyme-mediated lysosomal membrane leakage for targeted drug delivery.

Rationale: Employing in situ bioorthogonal catalysis within subcellular organelles, such as lysosomes, remains a challenge. Lysosomal membranes pose an intracellular barrier for drug sequestration, thereby greatly limiting drug accumulation and concentrations at intended targets. Here, we provide a proof-of-concept report of a nanozyme-based strategy that mediates in situ bioorthogonal uncaging reactions within lysosomes, followed by lysosomal escape and the release of uncaged drugs into the cytoplasm.Methods: A model system composed of a protein-based nanozyme platform (based on the transition metals Co, Fe, Mn, Rh, Ir, Pt, Au, Ru and Pd) and caged compound fluorophores was designed to screen for nanozyme/protecting group pairings. The optimized nanozyme/protecting group pairing was then selected for utilization in the design of anti-cancer pro-drugs and drug delivery systems.Results: Our screening system identified Pd nanozymes that mimic mutant P450BM3 activity and specifically cleave propargylic ether groups. We found that the intrinsic peroxidase-like activity of Pd nanozymes induced the production of free radicals under acid conditions, resulting in lysosomal membrane leakage of uncaged molecules into the cytoplasm. Using a multienzyme synergistic approach, our Pd nanozymes achieved in situ bioorthogonal catalysis and nanozyme-mediated lysosomal membrane leakage, which were successfully applied to the design of model pro-drugs for anti-cancer therapy. The extension of our nanozyme system to the construction of a liposome-based “all-in-one” delivery system offers promise for realizing efficacious in vivo tumor-targeted therapies.Conclusions: This strategy shows a promising new direction by utilizing nanotechnology for drug development through in situ catalyzing bioorthogonal chemistry within specific subcellular organelles.

Targeting Ovarian Solid Tumors by Elastin-Like Polypeptide Drug Conjugates: Current Trends and Future Prospectives.

Ovarian cancer is one of the leading causes of death worldwide. Polymers have low cytotoxicity and high functionalizability and are hence used for drug delivery systems, tissue engineering, and polymer therapeutics. In drug delivery systems, polymer-drug conjugates have shown considerable promise, especially in anticancer chemotherapy. Anticancer Drug Delivery Systems (DDS) deliver drugs to the tumor site leading to reduced exposure of the drugs to healthy cells and hence reduced side effects. Efforts have been made in the past to develop effective DDS using stimuli-responsive polymers like thermosensitive and pH-sensitive polymers. Elastin-like Polypeptides (ELP), one of the thermoresponsive polymers, have been identified as drug carriers in anticancer therapy. ELP-drug conjugates have the potential and can be used effectively in combination with hyperthermia for targeting drugs to solid tumors. This review reports on the use of ELPs in cancer therapy, its biomedical applications, and recent developments to target drugs to ovarian solid tumors.

Hollow microcapsule with pH-sensitive chitosan/polymer shell for in vitro delivery of curcumin and gemcitabine

The utilization of hollow structures for encapsulation and controlled release of drugs has attracted considerable attention in recent years. Among the different methods reported for fabrication of hollow polymer microcapsules, the layer-by-layer (LbL) assembly of oppositely charged polymers is of special importance. The pH-responsive capsules have attracted special interest as anti-cancer drug delivery systems due to the difference between normal and cancerous tissue. In this work, new pH-sensitive and biodegradable capsules were prepared based on the layer-by-layer (LbL) assembly of oppositely charged polyelectrolytes, chitosan (CS), and poly(ethylene glycol dimethacrylate-co-methacrylic acid) (EM). The obtained microcapsules were used for the delivery of two types of anticancer drugs including gemcitabine (Gem) and curcumin (Cur). The removal of the core was proved with transmission electron microscopy (TEM) confirming the spherical shape of the prepared hollow structure. The high performance of microcapsules was proven by encapsulation efficiency (EE%) and releasing efficiency (RE%) of above 84% and 82%, respectively. The high pH sensitivity of prepared microcapsules is due to the solubility of chitosan in acidic media. These microcapsules exhibit high cytotoxicity in a dose-dependent manner on the HCT-116 colorectal carcinoma cells. On the other hand, the desired results for the drug delivery of Gem and Cur demonstrate the applicability of prepared microcapsules for different drugs.

Functionalized Graphene Oxide as Drug Delivery Systems for Platinum Anticancer Drugs.

Graphene Oxide, prepared by the modified Hummer's method, was modified with a series of high polymers (polyethyleneimine, polyethylene glycol, chitosan) and Folic Acid for the delivery of platinum anticancer drugs including Cisplatin, Carboplatin, Oxaliplatin and Eptaplatin. Nanocarriers were successfully prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscope. Measurement of drug loading efficiency showed that these nanocarriers had the ability for effective delivery of the platinum anticancer drugs. The Maximum loading ratios of Cisplatin, Carboplatin, Oxaliplatin and Eptaplatin were 25.72, 161.08, 345.21 and 67.80μg/mg. Drug release experiments in the acid environment showed that the cumulative release rate of platinum anticancer drugs from nanocarriers was higher than that in the neutral environment. The cumulative release of all three nanocarriers in the acid environment reached above 60%. In vitro cytotoxicity assay showed that those nanocarriers had a low toxicity. The cell viability rates were above 80% for all three nanocarriers. Investigation of the anticancer activity in vitro showed that those drug delivery systems had the ability to inhibit the growth of the SKOV3 cell line. These results showed that those nanocarriers were suitable for the delivery of platinum anticancer drugs. Providing preliminary advice on the potential application of the combination of platinum anticancer drugs and the functionalized Graphene Oxide nanocarriers.

Paclitaxel - Combined Curcumin - Loaded PLA-TPGS - Based Nanoparticles Induce Apoptosis and Inhibit the Growth of Breast Cancer Cells and Multicellular Tumor Spheroids

Paclitaxel and curcumin have been reported as anti-cancer drugs. Here we presented a novel combination of paclitaxel and curcumin-loaded PLA-TPGS (PTX-Cur/PLA-TPGS) nanoparticles prepared by a modified solvent extraction/evaporation technique. These nanoparticles were well distributed and stable in water. This combination of paclitaxel and curcumin gave a higher efficiency of both drugs in cytotoxicity; induced apoptosis; and effect on cell cycles of KPL4 cell line in compare with the use of paclitaxel or curcumin alone or even a normal mixture of these two drugs. Furthermore, PTX-Cur/PLA-TPGS nanoparticles exhibited a powerful ability in preventing MCF7 spheroids growth. Interestingly, curcumin also functioned as both a drug and a label. Base on the autofluorescence of curcumin, the absorption of PTX-Cur/PLA-TPGS nanoparticles into MCF7 spheroids could be followed and calculated. These results suggested that the nanoparticle-drug combination may provide a promising multifunctional delivery system for anti-cancer drugs.

A dual-sensitive poly(amino acid)/hollow mesoporous silica nanoparticle-based anticancer drug delivery system with a rapid charge-reversal property

The negative-to-positive surface charge-reversal capability introduced can reduce the nonspecific cellular uptake of the nanosized anticancer drug delivery systems (DDSs) and enhance the endocytosis capability by cancer cells. In this article, a novel dual-sensitive anticancer DDS with a rapid charge-reversal property was reported. Hollow mesoporous silica nanoparticle (HMSN) with a high drug loading capacity was applied as the “nanocontainer” to package the drug doxorubicin hydrochloride (DOX), then was coated by poly(aspartic acid)-graft-1-(3-aminopropyl) imidazole (PASP-g-API) through the redox-sensitive disulfide bond to obtain the DDS DOX@HMSN–SS–PASP-API. The imidazole group was not ionized at pH 7.4, resulting in a negatively charged surface of the DDS. But in the slightly acidic tumor microenvironment, the ionization of the imidazole group rapidly reversed the surface charge of the carriers for better uptake by cancer cells. After the endocytosis, the disulfide bond linking PASP-g-API and HMSN could be interrupted in the reducing environment intercellular, leading to the DOX release. The rapid charge-reversal property of the carriers was demonstrated by the in vitro studies, and the cell experiments proved that the carriers could enter the cancer cells much easier in the weakly acidic environment. Drug release studies indicated that DOX@HMSN–SS–PASP-API could release ~97% loaded DOX within 5 days with the glutathione concentration of 10 mM, demonstrating its sensitivity to redox. Also, DOX@HMSN–SS–PASP-API at pH 6.5 showed the best therapeutic effect among all the DDS groups. This dual-sensitive system with a rapid charge-reversal property should be a good complement to the researches of anticancer DDSs.

HCT116 Cells Cytotoxic Response to Multifuctionalized 5- Fluorouracil MWCNTs Conjugates In Colorectal Cancer

Nanomaterials are the foundations of Nanotechnology, which are measured in nanoscales, Carbon nanotubes are one of the interesting nanomaterials, studied for over 25 years because of their superlative properties such as high surface area, electrical and thermal conductivity, high biocompatibility, flexibility, resistance to corrosion and nanosize. According to research, carbon nanotubes are applied in sensing, water treatment, and drug delivery, mainly used to deliver the anticancer drugs. In our work, functionalization of multi walled carbon nanotubes done by covalent and non-covalent functionation methods, covalent functionalization showed better dispersing efficiency in aqueous medium and compatible with biological systems with damaging the crystal lattice of carbon nanotubes. Non covalent functionalization helps to derivatized with active compounds, surface adsorption or attachment of various molecules or antibodies, which subsequently helps in targeting the site and to produce therapeutic effects. Different formulations prepared by functionalized MWCNTs and multiple functionalization of MWCNTs done by binding the drug and antibodies to prepare functionalized MWCNTs 5-Fluorouracil complexes. The Cytotoxicity assay was carried out for the obtained new targeting formulations to analyze the effect of all the formulations on HCT116 cell line. The percentage death was determined based on the viability of the cells in the appropriate vehicle controls. In this study, we report the successful functionalization, binding of 5 Fluorouracil, antibodies to MWCNTs, and cells viability of all prepared formulations for the development of novel carbon based anticancer drug delivery system. Functionalized MWCNTs-5-Fluorouracil antibodies composite at concentration above 2.5 µg/mL exhibited ≥ 50% cytotoxicity post normalization with compound control to negate precipitation observed with the compound. All the formulations showed the precipitations indicating antitumor activity and biocompatibility.

Quantum chemical analysis of 5-aminolevulinic acid anticancer drug delivery systems: Carbon nanotube, –COOH functionalized carbon nanotube and iron oxide nanoparticle

Drug delivery systems including the 5-aminolevulinic acid anticancer drug (ALA) and carbon nanotube (CN), COOH functionalized carbon nanotube (FCN) and iron oxide nanoparticle (ION) were examined. For each of the CN, FCN and ION nanocarriers, four (CN/ALA1-4), three (FCN/ALA1-3) and three (ION/ALA1-3) configurations were considered, respectively. All structures were optimized at B3LYP/6-31G(d,p) in aqueous solution. Dispersion corrections were considered using M06-2X density functional. Binding energies, solvation energies and the contribution of each configuration in the drug delivery system were calculated. The binding energies of FCN/ALA1-3 and ION/ALA1-3 are about the same and much larger than those of CN/ALA1-4. On the other hand, the solvation energies of ION/ALA1-3 are more negative than those of CN/ALA1-4 and FCN/ALA1-3, which is an important advantage for iron oxide nanoparticles. Quantum molecular descriptors indicate that the reactivity of ALA increases in the vicinity of CN, FCN and ION. The AIM analysis showed that the hydrogen bonds play important roles in FCN/ALA1-3 and ION/ALA1-3 configurations.

Dual-modified PCL-PEG nanoparticles for improved targeting and therapeutic efficacy of docetaxel against colorectal cancer

Polycaprolactone-poly (ethylene glycol) block copolymer (PCL-PEG) based nanoparticles were prepared for the intravenous administration of docetaxel (DTX). PCL-PEG-Tyr and PCL-PEG-Ang were synthesized by using tyrosine (Tyr) and angiopep-2 (Ang) as coupling ligands, and dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) were prepared. The physicochemical properties, in vitro drug release, in vitro cytotoxicity, in vitro cellular uptake efficiency, in vivo biodistribution and in vivo antitumor efficacy of PCL-PEG-based nanoparticles were investigated. The PCL-PEG-based nanoparticles were spherical with a mean diameter of 100 nm and high encapsulation efficiencies (> 85%). The results of in vitro drug release showed that the PCL-PEG-based nanoparticles loaded with DTX had sustained-release characteristics. For in vitro cytotoxicity tests, the dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) demonstrated the minimum IC50 value (2.94 µg/mL) compared with other PCL-PEG-based nanoparticles. In addition, the cellular uptake of coumarin-6 (C6) in HT29 cells was observed and determined in the PCL-PEG-Tyr/Ang nanoparticles group, which was significantly higher than that in the other PCL-PEG-based groups and C6 solution group. The results of in vivo imaging showed that dual-modified PCL-PEG nanoparticles had better tumor targeting than the other PCL-PEG-based nanoparticles. In the HT29 tumor-xenografted nude mice model, DTX-loaded PCL-PEG-Tyr/Ang nanoparticles also had a significantly higher inhibitory efficacy on tumor growth than Taxotere®-treated group. These results indicated that the dual-modified PCL-PEG-based nanoparticles (PCL-PEG-Tyr/Ang) could be a promising anticancer drug delivery system.