Cisplatin delivery,anticancer and antibacterial properties of Fe/SBA-16/ZIF-8 nanocomposite

Nanoformulation involving biocompatible MOFs and magnetic nanocarriers is an emerging multifunctional platform for drug delivery and tumor imaging in targeted cancer therapeutics. In this study, a nanocomposite has been developed comprising Fe/SBA-16 and ZIF-8 (Fe/S-16/ZIF-8) through ultrasonication. The drug delivery of cisplatin was studied using an automated diffusion cell system equipped with a flow type Franz cell. The anticancer activity of Fe/S-16/ZIF-8 was studied in vitro in MCF-7, HeLa cells and Human Foreskin Fibroblast (HFF-1) cells. XRD and d-spacing measurements of Fe/S-16/ZIF-8 using TEM revealed the presence of cubic-structured Fe₃O₄, γ-Fe₂O₄ (magnetite), and α-FeOOH (goethite) over an SBA-16/ZIF-8 nanocomposite. The composite showed a surface area of 365 m² g⁻¹, a pore size of 8.3 nm and a pore volume of 0.33 cm³ g⁻¹. VSM analysis of Fe/S-16/ZIF-8 showed that it possessed paramagnetic behavior with a saturated magnetization value of 2.39 emu g⁻¹. The Fe²⁺/Fe³⁺ coordination environment was characterized using diffuse reflectance spectroscopy. The cisplatin drug delivery study clearly showed the synergistic effects present in Fe/S-16/ZIF-8 with over 75% of cisplatin release as compared to that of Fe/S-16 and ZIF-8, which showed 56% and 7.5%, respectively. The morphology analysis of CP/Fe/SBA-16/ZIF-8 using TEM showed an effective transit of nanoparticles into MCF-7 cells. The lethal concentration (LC₅₀) of Fe/SBA-16/ZIF-8 for MCF-7 and HeLa cells is 0.119 mg mL⁻¹ and 0.028 mg mL⁻¹ at 24 h, respectively. For HFF-1 cells, the LC₅₀ is 0.016 mg mL⁻¹. The antibiofilm activity of Fe/SBA-16/ZIF-8 was investigated against biofilm-forming strains of drug resistant P. aeruginosa and MRSA by a microtiter tissue culture plate assay. Overall, nanosized ZIF-8 with a bioactive alkaloid imidazole inside the 3D cage type of SBA-16 pores is found to exhibit both anticancer and antibacterial properties. A Fe/S-16/ZIF-8 composite could be effectively used as a drug and drug delivery system against cancer and promote antibacterial activity.

The role of nano ZIF-8 in a Fe/SBA-16/ZIF composite has been explored as a potential anticancer drug and drug delivery system.     

Bifunctional folic-conjugated aspartic-modified Fe3O4 nanocarriers for efficient targeted anticancer drug delivery

Functionalization of nanocarriers has been considered the most promising way of ensuring an accurate and targeted drug delivery system. This study reports the synthesis of bifunctional folic-conjugated aspartic-modified Fe₃O₄ nanocarriers with an excellent ability to deliver doxorubicin (DOX), an anticancer drug, into the intercellular matrix. Here, the presence of amine and carboxylate groups enables aspartic acid (AA) to be used as an efficient anchoring molecule for the conjugation of folic acid (FA) (EDC–NHS coupling) and DOX (electrostatic interaction). Based on the results, surface functionalization showed little effect on the physicochemical properties of the nanoparticles but significantly influenced both the loading and release efficiency of DOX. This is primarily caused by the steric hindrance effect due to large and bulky FA molecules. Furthermore, in vitro MTT assay of B16–F1 cell lines revealed that FA conjugation was responsible for a significant increase in the cytotoxicity of DOX-loaded nanocarriers, which was also found to be proportional to AA concentration. This high cytotoxicity resulted from an efficient cellular uptake induced by the over-expressed folate receptors and fast pH triggered DOX release inside the target cell. Here, the lowest IC₅₀ value of DOX-loaded nanocarriers was achieved at 2.814 ± 0.449 μg mL⁻¹. Besides, further investigation also showed that the drug-loaded nanocarriers exhibited less or no toxicity against normal cells.

Aspartic acid was used as an anchoring molecule for the conjugation of folic acid and doxorubicin to Fe₃O₄ nanoparticles. The as-prepared bifunctional folic-conjugated aspartic-modified Fe₃O₄ nanocarrier was shown to be as an efficient targeted anticancer drug delivery.     

Magnetically responsive polycaprolactone nanocarriers for application in the biomedical field: magnetic hyperthermia,magnetic resonance imaging,and magnetic drug delivery

There are huge demands on multifunctional nanocarriers to be used in nanomedicine. Herein, we present a simple and efficient method for the preparation of multifunctional magnetically responsive polymeric-based nanocarriers optimized for biomedical applications. The hybrid delivery system is composed of drug-loaded polymer nanoparticles (poly(caprolactone), PCL) coated with a multilayer shell of polyglutamic acid (PGA) and superparamagnetic iron oxide nanoparticles (SPIONs), which are known as bio-acceptable components. The PCL nanocarriers with a model anticancer drug (Paclitaxel, PTX) were formed by the spontaneous emulsification solvent evaporation (SESE) method, while the magnetically responsive multilayer shell was formed via the layer-by-layer (LbL) method. As a result, we obtained magnetically responsive polycaprolactone nanocarriers (MN-PCL NCs) with an average size of about 120 nm. Using the 9.4 T preclinical magnetic resonance imaging (MRI) scanner we confirmed, that obtained MN-PCL NCs can be successfully used as a MRI-detectable drug delivery system. The magnetic hyperthermia effect of the MN-PCL NCs was demonstrated by applying a 25 mT radio-frequency (f = 429 kHz) alternating magnetic field. We found a Specific Absorption Rate (SAR) of 55 W g⁻¹. The conducted research fulfills the first step of investigation for biomedical application, which is mandatory for the planning of any in vitro and in vivo studies.

There are huge demands on multifunctional nanocarriers to be used in nanomedicine.     

Curcumin loaded zinc oxide nanoparticles for activity-enhanced antibacterial and anticancer applications

Zinc oxide nanoparticles and curcumin have been shown to be excellent antimicrobial agents and promising anticancer agents, both on their own as well as in combination. Together, they have potential as alternatives/supplements to antibiotics and traditional anticancer drugs. In this study, different morphologies of zinc oxide-grafted curcumin nanocomposites (ZNP–Cs) were synthesized and characterized using SEM, TGA, FTIR, XRD and UV-vis spectrophotometry. Antimicrobial assays were conducted against both Gram negative and Gram-positive bacterial stains. Spherical ZnO–curcumin nanoparticles (SZNP–Cs) and rod-shaped ZnO–curcumin nanoparticles showed the most promising activity against tested bacterial strains. The inhibition zones for these curcumin-loaded ZnO nanocomposites were consistently larger than their bare counterparts or pure curcumin, revealing an additve effect between the ZnO and curcumin components. The potential anticancer activity of the synthesized nanocomposites was studied on the rhabdomyosarcoma RD cell line via MTT assay, while their cytotoxic effects were tested against human embryonic kidney cells using the resazurin assay. SZNP–Cs exhibited the best balance between the two, showing the lowest toxicity against healthy cells and good anticancer activity. The results of this investigation demonstrate that the nanomatrix synthesized can act as an effective, additively-enhanced combination delivery/therapeutic agent, holding promise for anticancer therapy and other biomedical applications.

Curcumin-loaded ZnO nanocomposites act as an effective, synergistically-enhanced combination delivery/therapeutic agent, holding promise for anticancer and antimicrobial therapy with reduced toxicities.     

In-depth drug delivery to tumoral soft tissues via pH responsive hydrogel

A pH responsive nanoparticle–hydrogel hybrid drug delivery system was investigated for in-depth anticancer drug delivery to solid tumours. It consists of acid susceptible polymer nanoparticles loaded in a chitosan hydrogel. The hybrid formulation was characterized by UV-visible spectroscopy, FTIR, SEM, TEM, particle size analysis, zeta potential measurement and viscosity measurement. Drug encapsulation and nanoparticle loading efficiencies were found to be 48% and 72% respectively which describes the efficient interaction of the chemical entities in this hybrid drug delivery system. The hydrogel exhibited pH responsive behaviour: minimal drug and nanoparticle release at physiological pH but an increase in viscosity under acidic conditions and fast nanoparticle and drug release. The cytotoxicity of the drug loaded hydrogel was investigated against the MCF-7 breast cancer cell line along with the drug and nanoparticles without hydrogel. The drug loaded hydrogel showed a better cytotoxic effect on MCF-7 cancer cells. Thus, drug loaded nanoparticles containing hydrogel could be a better option for maximum drug distribution in tumours.

A pH responsive nanoparticle–hydrogel hybrid drug delivery system was investigated for in-depth anticancer drug delivery to solid tumours.     

A doxorubicin–platinum conjugate system: impacts on PI3K/AKT actuation and apoptosis in breast cancer cells

In recent years, the development of a nano-conjugate system for drug delivery applications has gained attention among researchers. Keeping this in mind, in this study, we developed a doxorubicin–platinum conjugate system that targeted breast cancer cell lines. To achieve this, we developed platinum nanoparticles using polyvinylpyrrolidone (PVP). High resolution-transmission electron microscopy (HR-TEM) revealed the occurrence of octopod-shaped platinum nanoparticles. Subsequently, doxorubicin (DOX) was conjugated on the surface of the as-prepared platinum octopods via an in situ stirring method. The physicochemical characterization of the doxorubicin–platinum conjugate system revealed that the PVP of PtNPs interacts with the NH₂ group of doxorubicin via electrostatic interaction/hydrogen bonding. Besides, the doxorubicin–platinum conjugate system exhibited a sustained drug release profile within the cancer cells. Furthermore, the evaluation of the in vitro anticancer efficacy of the doxorubicin–platinum conjugate system in breast cancer cells (MCF-7 and MDA-MB-231) unveiled the induction of apoptosis via intracellular ROS and DNA damage, rather than free DOX and PtNPs. Remarkably, we also perceived that the doxorubicin–platinum conjugate system was strong enough to down-regulate the PI3K/AKT signalling pathway. As a result, the tumour suppressor gene PTEN was activated, which led to the stimulation of a mitochondrion-based intrinsic apoptotic pathway and its downstream caspases, triggering cell death. Hence, our findings suggested that a biologically stable doxorubicin–platinum conjugate system could be an imperative therapeutic agent for anticancer therapy in the near future.

In recent years, the development of a nano-conjugate system for drug delivery applications has gained attention among researchers.     

Poly(N-vinylcaprolactam) containing solid lipid polymer hybrid nanoparticles for controlled delivery of a hydrophilic drug gemcitabine hydrochloride

Folic acid tagged and hydrophilic polymer containing solid lipid nanoparticles (SLNs) were formulated for the controlled and targeted delivery of gemcitabine, a hydrophilic drug. Drug loaded SLNs were prepared by double emulsion method and optimized by 3² level factorial design. Then, a hydrophilic polymer, namely, poly(N-vinylcaprolactam) (PVCL) was incorporated in the optimized SLN batch in the first aqueous phase (W1) to obtain solid lipid polymer hybrid nanoparticles (SLPHNs) that were further decorated with folic acid (F-SLPHNs). TEM analysis of SLNs and SLPHNs revealed the spherical shape with no aggregation while SLPHNs showed higher % EE. SLPHNs exhibited limited burst release of gemcitabine compared to SLNs as well as lower overall % release. All the formulations showed good cytocompatibility against MDA-MB-231 cell lines and folic acid-tagged hybrid particles (F-SLPHNs) showed remarkably higher cellular uptake.

A hydrophilic polymer, poly(N-vinylcaprolactam), incorporated into solid lipid nanoparticles (SLNs) imparts better encapsulation and controlled release of gemcitabine.     

Polymer grafted magnetic graphene oxide as a potential nanocarrier for pH-responsive delivery of sparingly soluble quercetin against breast cancer cells

In this work, polymer grafted magnetic graphene oxide (GO–PVP–Fe₃O₄) was successfully synthesized for efficient delivery of anticancer drug. Firstly, GO was functionalized with the hydrophilic and biocompatible polymer polyvinylpyrrolidone (PVP) and then grafted with magnetic nanoparticles (Fe₃O₄) through an easy and effective chemical co-precipitation method. Quercetin (QSR) as an anticancer drug was loaded onto the surface of GO–PVP–Fe₃O₄via non-covalent interactions. The drug loading capacity was as high as 1.69 mg mg⁻¹ and the synthesized magnetic nanocarrier shows pH-responsive controlled release of QSR. The cellular cytotoxicity of the synthesized nanocarrier with and without drugs was investigated in human breast cancer MDA MB 231 cells and their effects compared on non-tumorigenic epithelial HEK 293T cells. These results reveal that the drug loaded GO–PVP–Fe₃O₄ nanohybrid was found to be more toxic than the free drug towards MDA MB 231 cells and exhibits biocompatibility towards HEK 293T cells. Overall, a smart drug delivery system including polymer grafted magnetic graphene oxide as a pH-responsive potential nanocarrier could be beneficial for targeted drug delivery, controlled by an external magnetic field as an advancement in chemotherapy against cancer.

Polymer grafted magnetic graphene oxide (GO–PVP–Fe₃O₄) as an efficient nanocarrier for the delivery of anticancer drug quercetin.     

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.

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.     

Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration.

Clozapine, a lipophilic effective atypical antipsychotic drug, has very poor oral bioavailability (<27%) due to first pass effect. Clozapine solid lipid nanoparticles have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soylecithin 95%, poloxamer 188 and stearylamine as a positive charge inducer by hot homogenization followed by ultrasonication method. Particle size and charge measurements were made with Malvern Zetasizer. Pharmacokinetics of clozapine incorporated in solid lipid nanoparticles (SLNs), after intravenous (i.v.) administration to conscious male Wistar rats were studied. The aim of this research was to find out whether the bioavailability of clozapine can be improved by administering clozapine SLN duodenally to rats. Tissue distribution studies of clozapine SLN and suspension were carried out in Swiss albino mice. Average size and zeta potential of SLNs of different lipids with stearylamine ranged from 96.7+/-3.8 to 163.3+/-0.7 nm and 21.3+/-1.3 to 33.2+/-0.6 mV, respectively. AUC((0-infinity)) was increased (up to 2.91-fold) and clearance was decreased (up to 2.93-fold) when clozapine entrapped in SLNs with stearylamine were administered intravenously. Bioavailability of clozapine SLNs were 2.45- to 4.51-fold after intraduodenal administration compared with that of clozapine suspension. In tested organs, the AUC and MRT of clozapine SLNs were higher than those of clozapine suspension especially in brain and reticuloendothelial cell-containing organs. These results indicate that SLN are suitable drug delivery system for the improvement of bioavailability of lipophilic drugs such as clozapine.     

Biodistribution and targeting potential assessment of mucoadhesive chitosan nanoparticles designed for ulcerative colitis via scintigraphy

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis. Methods: CS-NPs were prepared by ionic gelation using tripolyphosphate. To specify pH sensitive delivery, CS–CN-NPs were coated with Eudragit FS 30D by using a solvent evaporation method. Different process parameters were evaluated, and the optimized formulation was characterized by particle size, size distribution, zeta potential and encapsulation efficiency before lyophilization. The lyophilized product was further subjected to Fourier-transform infrared spectroscopy, and particle morphology and in vitro drug release in different media were studied. Results: the kinetics of in vitro drug release from the CS–CN-NPs revealed sustained release behaviour of the developed carriers. In vivo biodistribution study by gamma-scintigraphy showed good accumulation of the developed nanocarriers in the colonic region. Conclusion: sustained and pH stimulated delivery of CN to the colon was successfully attained via coating of CS-NPs with Eudragit FS 30D to circumvent poor absorption and availability of CN.

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis.     

Diastereoselective synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives following hetero-Diels–Alder reaction and in vitro anticancer studies

The development of concise methods for the synthesis of small functionalised spirocyclic molecules is important in the search of new bioactive molecules. To contribute this, here we represent a diastereoselective oxa-hetero-Diels–Alder reaction for the synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives and studied their in vitro anticancer activities. Using previously less explored cyclic ketone i.e. indane-1,3-dione and 3-vinyl-2H-chromene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between “drug-like” molecules and natural products. Various spiro indanone fused pyrano[3,2-c]chromene derivatives were synthesized regiospecifically bearing a quaternary stereocenter in high yields (up to 85%) with excellent diastereoselectivity in toluene using 4 Å MS as additive under reflux condition at 120 °C. In vitro cytotoxic studies of these compounds against MCF-7 (breast cancer), HCT-116 (colon cancer), H-357 (oral cancer), MD-MB-231(Breast cancer) cell lines were evaluated by MTT {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide} assay in vitro. The screening results revealed that many of the compounds are showing moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed potent inhibitory activities in comparison to the commercial anticancer drug 5-fluorouracil (5-FU). Among the series, compound 3′c showed most potent cytotoxicity (15.0–27.5 μM) in three cancer cell lines (MCF-7, HCT-116 and MD-MB-231).

Synthesis of novel spiro indanone fused pyrano[3,2-c]chromene derivatives following hetero-Diels–Alder reaction has been demonstrated and evaluated for their in vitro anticancer activity.     

Indocyanine green conjugated lipid microbubbles as an ultrasound-responsive drug delivery system for dual-imaging guided tumor-targeted therapy

Herein, a multifunctional traceable and ultrasound-responsive drug targeted delivery system based on indocyanine green (ICG) and folic acid (FA) covalently conjugated lipid microbubbles (ILMBs–FA) is proposed. After encapsulation of the anticancer drug resveratrol (RV), the composite (RILMBs–FA) with fluorescence and ultrasound imaging capacity was studied for highly sensitive dual-imaging guided tumor targeted therapy. The resulting RILMBs–FA with an average particle size of 1.32 ± 0.14 μm exhibited good stability and biocompatibility characteristics. The RILMBs–FA featured a high RV loading ratio and the encapsulated RV has been demonstrated to be released from the microbubbles triggered by ultrasound (US) waves. In addition, it was found that the linked FA could facilitate a high cellular uptake of RILMBs–FA via the FA receptor-mediated endocytosis pathway. Compared to free RV and RILMBs, RILMBs–FA with US irradiation demonstrated a more significant tumor cell-killing efficacy mediated by apoptosis in vitro. Eight hours post intravenous injection of RILMBs–FA, the composites showed maximum accumulation in tumorous tissues according to in vivo fluorescence and US images. This ultimately led to the best tumor inhibition effect among all tested drugs under US irradiation. In vivo biosafety evaluations showed that RILMBs–FA featured high biocompatibility characteristics and no significant systemic toxicity over the course of one month. Taken in concert, these results demonstrate the versatility of this drug delivery system with dual-imaging and ultrasound-triggered drug release characteristics for potential future applications in cancer theranostics.

Schematic representation of the synthesis of RILMBs–FA and application in tumor therapy.     

Fabrication of green poly(vinyl alcohol) nanofibers using natural deep eutectic solvent for fast-dissolving drug delivery

Fast-dissolving drug delivery systems are essential to drug delivery owing to the enhanced drug solubility, controlled drug concentration, target and rapid drug delivery. In this study, we developed fast-dissolving drug delivery systems using honey and acetylsalicylic acid-embedded poly(vinyl alcohol) (PVA) nanofibers based on natural deep eutectic solvent (DES). The efficacy of our fast-dissolving drug delivery system was tested by incorporating honey and acetylsalicylic acid in the PVA nanofibers. Firstly, the morphology and structure of the functional PVA–DES nanofibers (PVA–DES–honey and PVA–DES–ASA) were observed and analyzed, which proved the successful preparation of functional PVA–DES nanofibers. NIH/3T3 and HepG2 cells incubated on the nanofiber had more than 90% of cell viability, suggesting our materials were biocompatible and non-toxic. The nanofiber materials dissolved rapidly in artificial saliva solutions, suggesting potential use of our materials for fast dissolving drug delivery in oral cavities. The honey incorporated PVA nanofiber (PVA–DES–honey) showed a total bacterial reduction of 37.0% and 37.9% against E. coli and S. aureus, respectively, after 6 hour incubation in bacterial cultures. Furthermore, in vivo study proved that the PVA–DES–honey nanofibers accelerated the wound healing process, and they improved the wound healing rate on rat skin to 85.2% after 6 days of surgery, when compared to the control PVA (68.2%) and PVA–DES (76.3%) nanofibers. Overall, the nanofiber materials reported in our study showed potential as a green and biocompatible fast-dissolving drug delivery system and can be used for pharmaceutical fields, such as antibacterial wound dressing and oral ulcer stickers.

We report an environmental friendly method to construct honey/ASA embedded poly(vinyl alcohol) nanofibers based on natural deep eutectic solvent for fast-dissolving drug delivery firstly.     

Molecular targets and anticancer activity of quinoline–chalcone hybrids: literature review

α,β-Unsaturated chalcone moieties and quinoline scaffolds play an important role in medicinal chemistry, especially in the identification and development of potential anticancer agents. The multi-target approach or hybridization is considered as a promising strategy in drug design and discovery. Hybridization may improve the affinity and potency while simultaneously decreasing the resistance and/or side effects. The conjugation of quinolines with chalcones has been a promising approach to the identification of potential anticancer agents. Most of these hybrids showed anticancer activities through the inhibition of tubulin polymerization, different kinases, topoisomerases, or by affecting DNA cleavage activity. Accordingly, this class of compounds can be classified based on their molecular modes of action. In this article, the quinolone–chalcone hybrids with potential anticancer activity have been reviewed. This class of compounds might be helpful for the design, discovery and development of new and potential multi-target anticancer agents or drugs.

α,β-Unsaturated chalcone moieties and quinoline scaffolds play an important role in medicinal chemistry, especially in the identification and development of potential anticancer agents.     

pH and redox dual-sensitive drug delivery system constructed based on fluorescent carbon dots

Herein, a pH and redox dual-responsive drug delivery system (CDs–Pt(iv)–PEG) was developed based on fluorescence carbon dots (CDs). In this system, cisplatin(iv) prodrug (Pt(iv)) was selected as a model drug to reduce toxic side effects. The aldehyde-functionalized monomethoxy polyethylene glycol (mPEG-CHO) was conjugated to CDs–Pt(iv) to form pH sensitive benzoic imine bond. Owing to the slightly acidic tumor extracellular microenvironment (pH 6.8), the benzoic imine bond was then hydrolyzed, leading to charge reversal and decrease in the hydration radius of the drug-carrying, which facilitated in vivo circulation and tumor targeting. Notably, the cytotoxicity of the drug delivery system on cancer cells was comparable to that of cisplatin, while the side effects on normal cells were significantly reduced. In addition, the system realized recognition of cancer cells by the high-contrast fluorescent imaging. In conclusion, the CDs–Pt(iv)–PEG system provided a promising potential for effective delivery of anticancer drugs and cancer cells screening.

The system is pH-responsive and redox-controlled release. And the charge reversal and size transitions of the system can enhance the targeted ability. Moreover, the system can recognize the cancer cells by the fluorescence imaging.     

Polymeric nanoparticles based on carboxymethyl chitosan in combination with painless microneedle therapy systems for enhancing transdermal insulin delivery

Biodegradable nanoparticles (NPs) have been frequently used as insulin transdermal delivery vehicles due to their grand bioavailability, better encapsulation, controlled release and less toxic properties. However, the skin''s barrier properties prevent insulin-loaded NP permeation at useful levels. Nowadays, microneedles have been spotlighted as novel transdermal delivery systems due to their advantages such as painlessness, efficient penetration and no hazardous residues. Herein, we introduce polymeric nanocarriers based on carboxymethyl chitosan (CMCS) for insulin delivery, combining with microneedle therapy systems, which can rapidly deliver insulin (INS) into the skin. The resulting CMCS-based nanocarriers are spherical nanoparticles with a mean size around 200 nm, which could generate supramolecular micelles to effectively encapsulate insulin (EE% = 83.78 ± 3.73%). A nanocrystalline microneedle array (6 × 6, 75/150 μm) was used to penetrate the stratum corneum (SC) for enhancing transdermal insulin delivery, while minimizing the pain sensation caused by intravenous injection. Compared with the transdermal rate of passive diffusion [2.77 ± 0.64 μg (cm⁻² h⁻¹)], the transdermal rate of the insulin-loaded NP combined with microneedle penetration shows a 4.2-fold increase [10.24 ± 1.06 μg (cm⁻² h⁻¹)] from permeation experiment in vitro. In vivo hypoglycemic experiments demonstrate the potential of using nanocarrier combination with microneedle arrays for painless insulin delivery through the skin in a clinical setting. Thus, the developed combination scheme of nanoparticles and microneedle arrays offers an effective, user-friendly, and low-toxicity option for diabetes patients requiring long-term and multiple treatments.

Biodegradable nanoparticles (NPs) have been frequently used as insulin transdermal delivery vehicles due to their grand bioavailability, better encapsulation, controlled release and less toxic properties.     

Novel non-mulberry silk fibroin nanoparticles with enhanced activity as potential candidate in nanocarrier mediated delivery system

Silk fibroin (SF) is well known for its excellent biocompatible properties facilitating its application in the field of biomedical engineering through different biomaterial fabrications in the recent era. Here in this study, novel nanoparticles from non-mulberry SF of Antheraea assamensis were fabricated, characterized and evaluated for its applicability as nanocarrier. Fabricated nanoparticles were initially compared with prevailing SF nanoparticles from Bombyx mori. Fabricated A. assamensis silk fibroin nanoparticles (AA-SFNps) were found to be lesser in size (80–300 nm in diameter) than B. mori silk fibroin nanoparticles (BM-SFNps) (120–500 nm in diameter). When checked for stability, AA-SFNps were found to be more stable than BM-SFNps in biological media. FTIR and XRD studies revealed persistence of structural properties even after fabrication. TGA and DSC studies showed AA-SFNps to be thermally more stable than BM-SFNps without any cytotoxicity (MTT assay). On loading with model drug Doxorubicin hydrochloride (DOX), AA-SFNps exhibited an encapsulation efficiency of 94.47% with 11.81% loading of the anticancer drug. Cumulative release study revealed highest percentage release of DOX (42.1 ± 0.4%) at pH 5.2 on day 7 in comparison to pH 7.4 and 8.0. Sustained release profile of the DOX loaded AA-SFNps (AA-SFNps-DOX) was clearly reflected and it was found to be highly cytotoxic against triple negative MDA-MB-231 cells in comparison to free DOX at different time points. Overall, this study showed the efficacy of the AA-SFNps as a nanocarrier for future drug delivery applications.

Novel Antheraea assamensis silk fibroin nanoparticles (AA-SFNps) exhibiting enhanced activity as doxorubicin hydrochloride (DOX) loaded nanocarriers for future drug delivery applications.     

Naproxen release aspect from boron-doped carbon nanodots as a bifunctional agent in cancer therapy

In this present study, boron–carbon nanodots were synthesized by the hydrothermal method. Boron–carbon nanodots were prepared by varying the concentration ratios of boronic acid and citric acid: 1 : 25, 2 : 1, and 25 : 1, respectively. The precursors were then poured into a Teflon autoclave and heated at 240° for 4 h. This research aims to synthesise and evaluate the potential of boron–carbon nanodots as a bioimaging agent and naproxen delivery carrier. An X-ray diffractogram showed that the boron–carbon nanodots were amorphous. To analyse the functional groups, FTIR and XPS analysis was carried out. Spectrofluorometric analysis (λ_ex 320 nm) showed that the formulation of boron–carbon nanodots 2 : 1 (BCD 2 : 1) has the most ideal fluorescent properties at λ_em 453 nm, whereas UV-vis analysis showed λ_max at 223 nm, with a quantum yield of 52.29%. A confocal laser scanning micrograph and toxicity test (MTT assays) showed that boron–carbon nanodots delivered naproxen efficiently with loading amount and loading efficiency of naproxen 28% and 65%, respectively. Furthermore, it induced an anticancer effect in HeLa cells. This result indicated that boron–carbon nanodots can be used as a bioimaging agent and naproxen delivery carrier.

In this present study, boron–carbon nanodots were synthesized by the hydrothermal method.     

Controlled delivery of a protein tyrosine phosphatase inhibitor,SHP099, using cyclodextrin-mediated host–guest interactions in polyelectrolyte multilayer films for cancer therapy

The Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) is a key enzyme in pathways regulating tumor growth signaling, and recently gained interest as a promising anticancer drug target. Many SHP2 inhibitors are currently under development, including SHP099, which has shown potent anticancer activity at low concentrations in vivo. In this work, we developed multilayer coatings for localized delivery of SHP099 to improve upon current cancer therapies. Layer-by-layer self-assembly was used to develop films composed of chitosan and poly-carboxymethyl-β-cyclodextrin (PβCD) for the delivery of SHP099. SHP099 was successfully loaded into multilayer films via host–guest interactions with PβCD. Nuclear magnetic resonance spectroscopy confirmed the occurrence of this supramolecular assembly by identifying the interaction of specific terminal SHP099 protons with the protons of the CD. SHP099 release from assembled films was detected over 96 hours, and was found to inhibit colony formation of human breast adenocarcinoma cells in vitro. These multilayer films have the potential to be used in a range of anticancer applications and overcome common complications of systemic chemotherapeutic administration, while maximizing SHP099 efficacy.

Controlled delivery of a potent anticancer drug, SHP099, after supramolecular complexation into a versatile multilayer film.