Functionalized chitosan with super paramagnetic hybrid nanocarrier for targeted drug delivery of curcumin

Recently, hydrophobically functionalized polymers have been deployed as carriers to improve the encapsulation of hydrophobic drugs. The metal nanocomposites are extensively used to improve the biocompatibility of the formulation and target the drug to the specialized site. In our current study, naphthalene acetate (NAA) was incorporated into the amine group of chitosan to form a hydrophobically functionalized chitosan–NAA drug delivery carrier. The calcium ferrite nanoparticles (CFNP) were embedded in the chitosan–NAA matrix to form a super paramagnetic hybrid nanocarrier for controlled curcumin drug delivery. Various analytical techniques were performed to ensure the functional group modifications, thermal stability, surface nature and morphological behavior of synthesized hybrid carriers. The maximum encapsulation efficiency of 93.6% was obtained under the optimized conditions of drug to chitosan–NAA at 0.1, CFNP to chitosan–NAA at 0.75 and TPP to chitosan–NAA at 1.0 (w/w) ratios, respectively, by adapting Taguchi method. Drug release studies were conducted to determine the effect of pH, drug loading concentrations and magnetic field responses. The drug release data were fitted to various kinetic release models to understand the drug release mechanism. The biocompatibility of the hybrid material was tested using L929 mouse fibroblast cells. The cytotoxicity test against breast cancer cells (MCF-7) was also performed to study the anticancer property of the hybrid paramagnetic material. The prepared curcumin-loaded chitosan–NAA/CFNP was very active against cancer cells in comparison to the normal cells. The results confirmed the applicability of the hybrid nanocarriers in cancer cell-targeted drug delivery.     

Synthesis of hollow maghemite (-Fe2O3) particles for magnetic field and pH-responsive drug delivery and lung cancer treatment

The development of smart stimuli-responsive materials for drug delivery offers new opportunities for precise drug release and cancer chemotherapy. A combination of more than one stimuli is highly desirable to further maximize the therapy by taking the advantages of various unique merits. Herein, we employed polyethylene glycol (PEG) functionalized γ-Fe₂O₃ particles (γ-Fe₂O₃/PEG) as a novel magnetic drug carrier for doxorubicin (DOX) delivery. The results showed that the γ-Fe₂O₃/PEG exhibited excellent thermal effects under alternating magnetic field (AMF), high magneto-thermal stability, and large DOX loading capacity. Furthermore, the effects of pH and AMF on the DOX drug release were studied. It was discovered that DOX loaded γ-Fe₂O₃/PEG carriers were highly responsive to both AMF and pH, resulting in significantly improved cancer cell killing capability over a single stimulus. The magnetic and pH responsive drug delivery system provided a new opportunity to minimize the side effects and maximize the therapeutic efficiency of lung cancer treatment.     

Supercritical carbon dioxide–assisted synthesis of stimuli-responsive magnetic poly(N-isopropylacrylamide)–ferrite biocompatible nanocomposites for targeted and controlled drug delivery

Supercritical carbon dioxide–assisted synthesis of poly(N-isopropylacrylamide)–ferrite nanocomposites was carried out by polymerization reaction of N-isopropyl acrylamide monomer in the presence of ferrite nanoparticles. They were characterized by Fourier transform infrared, X-ray diffraction, transmission electron microscopy, atomic force microscopy, and vibrating sample magnetometry analysis. Drug loading and release profiles were studied. Nanomaterials showed pH-dependent drug release profile. Polymer nanocomposites in comparison to ferrite nanoparticles showed impressive drug release activity, with a release percent of 20.98–76.54%, and greater biocompatibility in breast cancer cells, with a cell viability of 81–93%. This pH-dependent drug release activity and magnetic property of polymer nanocomposites can be used for controlled and targeted drug delivery.     

Development of multifunctional cobalt ferrite/hydroxyapatite nanocomposites by microwave assisted wet precipitation method: A promising platform for synergistic chemo-hyperthermia therapy

Functional nanocomposites capable of multimodal therapy hold great potential to improve the efficiency of cancer therapy. Herein, we report a magnetic nanocomposite of cobalt ferrite/hydroxyapatite followed by loading a chemotherapeutic drug (5-fluorouracil, FU) to construct the intelligent drug delivery system and/or hyperthermia carrier. To do that, cobalt ferrite/hydroxyapatite nanocomposite was successfully synthesized by microwave assisted wet precipitation method, subsequently, FU loaded onto the formed composites through adsorption method. This nanocomposite exhibits ferromagnetic behaviour with a magnetic saturation value of approximately 2.5–8.2 emu/g. Upon alternating magnetic field, it could generate hyperthermia temperature within a short time (43°C in 4.5 min) and facilitate the release of encapsulated FU from the composite with enhanced release rate. These multifunctional carriers also demonstrate a noticeable proliferative activity against healthy fibroblast cells (L929) and suppressed growth against osteosarcoma cells (MG63). Therefore, this studied nanoplatform might be a promising candidate for synergistic chemo-hyperthermia therapy.     

Graphene oxide/zinc ferrite nanocomposite loaded with doxorubicin as a potential theranostic mediu in cancer therapy and magnetic resonance imaging

Hybrid functional biomaterials are attracting increasing interest due to their biocompatibility and therapeutic and diagnostic characteristics. The theranostic properties of functional biomaterials favor their application. When these materials are responded to stimuli, they confer target site delivery. Although various types of nanocomposites have been developed for drug delivery and diagnostics, no ideal composites have been reported yet. Here, we report the synthesis of graphene oxide–zinc ferrite hybrid nanocomposites (GO-ZnFe₂O₄) conjugated with doxorubicin (GO-ZnFe₂O₄/DOX) for cancer therapy and magnetic resonance (MR) imaging-based diagnosis. The optical properties, crystal phase, particle size, functional groups, elemental composition, surface morphology, and magnetism of GO-ZnFe₂O₄ nanocomposites were characterized using state-of-the-art available techniques, including Fourier-Transform Infrared Spectroscopy (FTIR), Ultraviolet visible spectroscopy (UV–Vis), Transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Dynamic light scattering (DLS), Vibrating sample magneto meter (VSM) Scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectra (XPS). The in vitro analysis showed that GO-ZnFe₂O₄ conjugated with DOX is more cytotoxic than GO-ZnFe₂O₄. GO-ZnFe₂O₄/DOX induced the production of reactive oxygen species (ROS), which induced damage to nuclear DNA and mitochondrial DNA (mtDNA) when internalized by cells. This damage consequently drove mitochondrial malfunction and ultimately the apoptosis of cancer cells. Further studies were performed to investigate the diagnostic efficacy of these nanocomposites using MR imaging. GO-ZnFe₂O₄/DOX nanocomposites were developed and successfully employed in the MR imaging of HeLa cells. As shown in the present study, GO-ZnFe₂O₄/DOX might play a potential role in the development of chemotherapy and noninvasive MR imaging of tumor cells.     

Multifunctional hybrid magnetite nanoparticles with pH‐responsivity,superparamagnetism and fluorescence

Multifunctional hybrid nanoparticles, Fe₃O₄@poly[(2‐dimethylamino)ethyl methacrylate]‐block‐poly(2‐hydroxyethyl methacrylate)‐graft‐carbazole, with pH‐responsivity, superparamagnetism and fluorescence for targeted drug delivery and release have been synthesized. The nanoparticles have a core‐shell structure as determined from transmission electron microscopy, pH‐responsivity as determined from hydrodynamic radius analysis, superparamagnetism as determined from vibrating sample magnetometry and fluorescence as determined from fluorescence spectroscopy and fluorescence microscopy. The release behavior of model drug progesterone indicates that the release rate can be effectively controlled by altering the pH of the environment. The multifunctional nanoparticles could be applied extensively in targeted drug delivery and release, and with fluorescence they can serve as efficient tracers to record magnetic targeting routes. Copyright © 2011 Society of Chemical Industry     

A Novel Stimuli-Responsive Magnetite Nanocomposite as De Novo Drug Delivery System

A novel stimuli-responsive magnetite nanocomposite as de novo drug delivery system for cancer chemotherapy is developed successfully through the incorporation of magnetite nanoparticles into PEG-b-(PNIPAAm-b-PAA)₂ copolymer. The chemical structures of samples were characterized using FTIR and ¹H NMR spectroscopies. Furthermore, thermal property, morphology, size, and magnetic properties of the nanocomposite were investigated. The DOX loading and encapsulation efficiencies as well as stimuli-responsive drug release ability of the nanosystem were studied. As results, at pH 5.3 and temperature of 41°C the nanocomposite exhibited higher drug release values, which qualified it for cancer chemotherapy according to especial features of cancerous tissue.     

Nanotechnology-based combinational drug delivery systems for breast cancer treatment

Modern chemotherapeutic anticancer treatments have come a long way in the fight against breast cancer, thus bringing science closer to a cure. However, the nature of these drugs is to attack both cancerous and non-cancerous cells at the same time. In our studies, we synthesized Magnetic Cyclodextrin-polyurethane based nano-composite (Fe₃O₄-ECA-PU-CD) which is a drug delivery system using a biocompatible magnetic polymer that directs chemotherapeutic drugs to cancerous regions in the body with an external magnet. This nano-composite was able to facilitate the loading and simultaneous release of the hydrophilic antitumor drug Doxorubicin (DOX) along with the hydrophobic antitumor drug docetaxel. The composite was made using a simple co-precipitation method with magnetic nano-particles (MNPs) followed by a silica coating process and an in situ polymerization process. Verification of synthesis for the drug carrier was carried out using techniques such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and a vibrating sample magnetometer (VSM) to measure magnetic properties. Drug loading and release efficiencies were monitored using an HPLC-UV detector. Finally, an MTT assay was performed in order to evaluate the biocompatibility and toxicity of the synthetic nano-composite on MCF7 cell lines. Our findings present a new biocompatible drug delivery system with a high capacity for loading and directing two different chemotherapeutic drugs simultaneously to cancer sites with little to no toxicity to the surrounding non-cancerous cells. These studies present a viable tool for cancer treatment and research where the cancer is efficiently removed while the patient remains healthy.     

Influence of folate conjugation on the cellular uptake degree of poly(allylamine hydrochloride) microcapsules

The microcapsules in drug delivery systems can prevent degradation of drugs and help to control the release rate. To enhance the targeted delivery effect of the microcapsules to cancer cells, some specific ligands such as folic acid (FA) are necessarily further conjugated. Herein, covalent poly(allylamine hydrochloride) (PAH) multilayers were fabricated on CaCO₃ microparticles under the cross‐linking of glutaraldehyde, which were further immobilized with different amount of FA molecules via the spacer of diamino terminated poly(ethylene glycol) (PEG). As a comparison study, four types of microcapsules, i.e., the PAH capsules, the PAH capsules grafted with PEG, and the PAH capsules conjugated with two different amount of FA via the PEG spacer were prepared. Their chemical and physical structures were confirmed by infrared spectroscopy, UV–vis spectroscopy and scanning electron microscopy. In vitro cell culture found that the cellular uptake of the PAH capsules grafted with PEG was reduced significantly compared with that of the pure PAH capsules. The FA‐modified microcapsules could be selectively delivered into HepG2 tumor cells which overexpress FA receptors but not into the endothelial cells. The number of HepG2 cells which ingested the FA‐conjugated capsules showed a positive correlation with FA amount. The results indicate that these FA conjugated capsules have a high selectivity to be delivered to tumor cells, endowing them with a larger opportunity functioning as targeted delivery vehicle for anticancer drugs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Layer-by-Layer Engineered Superparamagnetic Polyelectrolyte Hybrid Hollow Microspheres With High Magnetic Content as Drug Delivery System

Polyelectrolyte hybrid hollow microspheres with sandwich structure of about 450 nm have been accomplished by layer-by-layer self-assembling of two modified ferroferric oxide nanoparticles, lysine modified ferroferric oxide nanoparticles (Fe₃O₄-LYs) and citrate modified ferroferric oxide nanoparticles (Fe₃O₄-CA), as the main assembling materials via electrostatic interaction for the first time. They are superparamagnetic with saturation magnetization of 45.69 emu/g, revealing their high magnetic content of 70%. As drug delivery system, they also exhibited pH-stimuli responsive controlled release of an anticancer drug doxorubicin, following the Fickian diffusion model. Their unique structure and high magnetic content make them good candidate for targeted delivery.     

H2O2-Responsive Organosilica-Doxorubicin Nanoparticles for Targeted Imaging and Killing of Cancer Cells Based on a Synthesized Silane-Borate Precursor

Doxorubicin (Dox) is a widely used fluorescent chemotherapy drug. Its primary delivery systems, based on physical adsorption to silica nanoparticles, can lead to low drug loading. Direct loading of Dox via covalent bonds during the formation of silica nanoparticles has never been reported. In this work, we designed and synthesized a silane-borate precursor, which contains not only an alkoxysilane moiety to form organosilica nanoparticles but also a phenylboronic acid moiety to react with diol-containing compounds. Using this compound, the covalent loading of Dox during the preparation of organosilica nanoparticles was effectively realized with a high drug loading content up to 22.4 %. Further modification by hyaluronic acid (HA) bestowed the Si-Dox@HA nanoparticles with the ability to target CD44-overexpressing cancer cells. The Si-Dox@HA nanoparticles exhibited H₂O₂-responsive release of about 80 % Dox and displayed seven-fold selectivity for killing cancer cells over normal cells, relative to Dox and Si-Dox nanoparticles. Moreover, these Si-Dox@HA nanoparticles are also suitable for targeted fluorescence imaging of CD44-overexpressing cancer cells.     

Guided molecular missiles for tumor-targeting chemotherapy--case studies using the second-generation taxoids as warheads

A long-standing problem in cancer chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Therefore, the development of innovative and efficacious tumor-specific drug delivery protocols or systems is urgently needed. A rapidly growing tumor requires various nutrients and vitamins. Thus, tumor cells overexpress many tumor-specific receptors, which can be used as targets to deliver cytotoxic agents into tumors. This Account presents our research program on the discovery and development of novel and efficient drug delivery systems, possessing tumor-targeting ability and efficacy against various cancer types, especially multidrug-resistant tumors. In general, a tumor-targeting drug delivery system consists of a tumor recognition moiety and a cytotoxic warhead connected directly or through a suitable linker to form a conjugate. The conjugate, which can be regarded as a "guided molecular missile", should be systemically nontoxic, that is, the linker must be stable in blood circulation, but upon internalization into the cancer cell, the conjugate should be readily cleaved to regenerate the active cytotoxic warhead. These novel "guided molecular missiles" are conjugates of the highly potent second-generation taxoid anticancer agents with tumor-targeting molecules through mechanism-based cleavable linkers. These conjugates are specifically delivered to tumors and internalized into tumor cells, and the potent taxoid anticancer agents are released from the linker into the cytoplasm. We have successfully used omega-3 polyunsaturated fatty acids, in particular DHA, and monoclonal antibodies (for EGFR) as tumor-targeting molecules for the conjugates, which exhibited remarkable efficacy against human tumor xenografts in animal models. We have developed self-immolative disulfide linkers wherein the glutathione-triggered cascade drug release takes place to generate the original anticancer agent. The use of disulfide linkers is attractive beacuse it takes into account the fact that the concentration of glutathione is much higher (>1000 times) in tumor cells than in blood plasma. In order to monitor and elucidate the mechanism of tumor-targeting, internalization, and drug release, several fluorescent and fluorogenic probes using biotin as the tumor-targeting module were developed and used. Then, the progressive occurrence of the designed receptor-mediated endocytosis, drug release, and drug binding to the target protein (microtubules) has been successfully observed and confirmed by means of confocal fluorescence microscopy. These "guided molecular missiles" provide bright prospects for the development of highly efficacious new generation drugs for cancer chemotherapy.     

Preparation and functional study of pH-sensitive amorphous calcium phosphate nanocarriers

Recently, multifunctional nanoparticles have shown great prospects in cancer treatment, which have the ability to simultaneously deliver the drug, image and target tumor cells. In this paper, we designed a luminescent nanoparticles platform based on hydrothermal hyaluronic acid/amorphous calcium phosphate (HA-FCNs/ACP) with multifunctional properties for drug delivery, bio-imaging, and targeting treatment. HA-FCNs/ACP shows an ability to load curcumin (Cur) with pH-sensitive responsive drug release behavior and excellent biocompatibility. HA-FCNs/ACP dispersed in the cytoplasm through the overexpressed CD44 receptor that is actively targeted into human lung cancer cells (A549 cells). Meanwhile, the viability of A549 cells was significantly inhibited in vitro. The prepared HA-FCNs and HA-FCNs/ACP both exhibit excellent targeted bioimaging performance on cancer cells. Hence, the as-prepared nanoparticles have promising applications in treating tumor disease.     

Lipid polymer hybrid carrier systems for cancer targeting: A review

Cancer has been the most deleterious disease since few decades and its prevalence is increasing day by day. Scientists have developed many novel carrier systems to modify the delivery of anticancer drugs specifically toward the cancer sites. Liposomes seemed to be the particles of choice to carry anticancer drugs owing to their biomembrane-friendly structure. However, poor stability and storage problems remain a drawback. Polymeric nanoparticles (PNPs) offer their rigid structure making controlled release of drugs possible. PNPs also maintain their integrity for a longer period of time. Recently, the benefits of the two carrier systems mentioned above have been combined into a single hybrid carrier system, i.e., lipid polymer hybrid nanoparticles. Such a setting makes a useful carrier system taking advantages of both the counterparts and minimizing their limitations at the same time. In this review, special types of lipid and polymer hybrid structures are discussed in detail. Also the methods of preparation along with controlling formulation parameters have been discussed. Various targeting moieties have been enlisted along with their mechanisms of active targeting. These moieties can be functionalized onto the surfaces of these hybrid particles. Special focus has been given to the colorectal cancer, throwing light upon its prevalence and already available treatment options. Lipid polymer hybrid nanoparticles enable the researchers to formulate a carrier system that will be able to provide targeted anticancer drug delivery.     

Preparation of hydroxyapatite-calcium ferrite composite for application in loading and sustainable release of amoxicillin: Optimization and modeling of the process by response surface methodology and artificial neural network

In this research, a merit carrier consisting of hydroxyapatite and calcium ferrite (HAp-CaFe₂O₄) was prepared via a convenient procedure and characterized using a series of techniques, including XRD, FE-SEM, TEM, EDS mapping, BET/BJH, VSM, and TGA. The loading of Amoxicillin (AMX) onto HAp-CaFe₂O₄ was optimized and modeled by two powerful approaches, namely response surface methodology (RSM) and artificial neural network (ANN). RSM-optimized results demonstrated that the maximum drug loading efficiency was 91.76% at a carrier dosage of 1.2 g, a drug concentration of 30 mg L^?1, and a pH of 6.5 within a stipulated time of 60 min. ANN modeling revealed that the pH of the solution had a dramatic effect with a 35% impact on the drug loading process. The downloading of AMX by HAp-CaFe₂O₄ was consistent with pseudo-2nd order and intra-particle diffusion kinetics models as well as the Temkin isotherm model, implying the chemisorption of the drug molecules on the carrier. The AMX release was evaluated at different pHs, and it was revealed that the sustained and prolonged drug evacuation occurred in the neutral medium as compared to acidic and basic media. The conformity of the drug release kinetics to the Korsmeyer-Peppas model indicated that the Fickian diffusion dominated the AMX release. The MTT assay showed the biocompatibility and safety of HAp-CaFe₂O₄ toward A549 cell lines.In summary, as-prepared HAp-CaFe₂O₄ can be regarded as a biocompatible and stimuli-responsive carrier for controlled and targeted drug delivery systems.     

A magnetic polypeptide nanocomposite with pH and near-infrared dual responsiveness for cancer therapy

A magnetic polypeptide nanocomposite with pH and near-infrared (NIR) dual responsiveness was developed as a drug carrier for cancer therapy, which was prepared through the self-assembly of Fe₃O₄ superparamagnetic nanoparticles, poly(aspartic acid) derivative (mPEG-g-PDAEAIM) and doxorubicin (DOX) in water. Fe₃O₄ nanoparticles were prepared to provide the superparamagnetic core of nanocomposites for tumor targeting via chemical co-precipitation. The protonable imidazole groups of mPEG-g-PDAEAIM with a pKa of ~7 were accountable for the pH-responsiveness of nanocomposites. The photothermal effect of nanocomposites under the irradiation of NIR laser was induced via the interactions between dopamine groups of mPEG-g-PDAEAIM and Fe₃O₄ superparamagnetic nanoparticles to trigger the drug release. NMR, FT-IR, TEM, hysteresis loop analysis and MRI were utilized to characterize the materials. The DOX loaded nanocomposites exhibited pH-responsive and NIR dependent on/off switchable release profiles. The nanocomposites without drug loading (Fe₃O₄@mPEG-g-PDAEAIM) showed excellent biocompatibility while DOX loaded nanocomposites caused MCF-7 cells’ apoptosis due to the photothermal/chemotherapy combination effects. Overall, the pH and near-infrared dual responsive magnetic nanocomposite had a great potential for cancer therapy.     

Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment

In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.     

Aptamer-Aptamer Chimera for Targeted Delivery and ATP-Responsive Release of Doxorubicin into Cancer Cells

Aptamers offer a great opportunity to develop innovative drug delivery systems that can deliver cargos specifically into targeted cells. In this study, a chimera consisting of two aptamers was developed to deliver doxorubicin into cancer cells and release the drug in cytoplasm in response to adenosine-5′-triphosphate (ATP) binding. The chimera was composed of the AS1411 anti-nucleolin aptamer for cancer cell targeting and the ATP aptamer for loading and triggering the release of doxorubicin in cells. The chimera was first produced by hybridizing the ATP aptamer with its complementary DNA sequence, which is linked with the AS1411 aptamer via a poly-thymine linker. Doxorubicin was then loaded inside the hybridized DNA region of the chimera. Our results show that the AS1411–ATP aptamer chimera was able to release loaded doxorubicin in cells in response to ATP. In addition, selective uptake of the chimera into cancer cells was demonstrated using flow cytometry. Furthermore, confocal laser scanning microscopy showed the successful delivery of the doxorubicin loaded in chimeras to the nuclei of targeted cells. Moreover, the doxorubicin-loaded chimeras effectively inhibited the growth of cancer cell lines and reduced the cytotoxic effect on the normal cells. Overall, the results of this study show that the AS1411–ATP aptamer chimera could be used as an innovative approach for the selective delivery of doxorubicin to cancer cells, which may improve the therapeutic potency and decrease the off-target cytotoxicity of doxorubicin.     

Nanobiofunctionalized chitosan nanocomposite hydrogel as a highly biocompatible cancer drug carrier

A bio-inspired drug carrier was developed by dual functionalization of chitosan using L-glutamic acid (GA) and phyto-synthesized zinc oxide nanoparticles (ZNPs). A highly porous, three-dimensional network of nanocomposite hydrogel (GA-CHGZ) was obtained upon cross-linking chitosan using biomass-derived dialdehyde cellulose. The hydrogel was optimally loaded with naringenin (NRG) and further characterized using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and swelling studies. An enhanced NRG loading efficiency of 85.23% was obtained using functionalized hydrogel compared to 52.54% using non-functionalized hydrogel. Delivery studies displayed a maximum release of 69.63% for 1.0 mg/ml of initial NRG concentration at pH 5, which is a highly preferred condition for cancer therapeutics. While ZNPs’ embedment was instrumental in improving the NRG loading and delivery rates, the GA conjugation increased the stability of NRG in the GA-CHGZ, aiding sustained NRG release, which followed a non-Fickian diffusion mechanism with polymer swelling. Antimicrobial potential was explored against Staphylococcus aureus and Trichophyton rubrum strains. The biocompatibility assay using L929 normal cells showed enhanced cell proliferation characteristics for the materials, revealing significant cell viability. The anticancer activity of NRG tested against A431 human skin carcinoma cells increased up to nine-fold with a reduced IC₅₀ value when a functionalized hydrogel was used instead of pure NRG without the nanocomposite carrier. Thus, the bio-functionalized drug–carrier system has a promising application for wound healing and topical skin cancer therapies.     

Targeted Nanoparticles Harboring Jasmine-Oil-Entrapped Paclitaxel for Elimination of Lung Cancer Cells

Selectively targeted drug delivery systems are preferable chemotherapeutic platforms, as they specifically deliver the drug cargo into tumor cells, while minimizing untoward toxic effects. However, these delivery systems suffer from insufficient encapsulation efficiency (EE), encapsulation capacity (EC), and premature drug release. Herein, we coencapsulated paclitaxel (PTX) and Jasmine oil (JO) within PEG-PCL nanoparticles (NPs), with an average diameter < 50 nm, selectively targeted to non-small cell lung cancer (NSCLC) cells, via S15-aptamer (APT) decoration. JO was selected as an “adhesive” oily core to enhance PTX entrapment, as JO and PTX share similar hydrophobicity and terpenoid structure. JO markedly enhanced EE of PTX from 23% to 87.8% and EC from 35 ± 6 to 74 ± 8 µg PTX/mg PEG-PCL. JO also markedly increased the residual amount of PTX after 69 h, from 18.3% to 65%. Moreover, PTX cytotoxicity against human NSCLC A549 cells was significantly enhanced due to the co-encapsulation with JO; the IC₅₀ value for PTX encapsulated within JO-containing APT-NPs was 20-fold lower than that for APT-NPs lacking JO. Remarkably, JO-containing APT-NPs displayed a 6-fold more potent cell-killing, relatively to the free-drug. Collectively, these findings reveal a marked synergistic contribution of JO to the cytotoxic activity of APT-NP-based systems, for targeted PTX delivery against NSCLC, which may be readily applied to various hydrophobic chemotherapeutics.