Sustained Release Of Doxorubicin Research Articles

Polydopamine-functionalized calcium-deficient hydroxyapatite 3D-printed scaffold with sustained doxorubicin release for synergistic chemo-photothermal therapy of osteosarcoma and accelerated bone regeneration

Interior bone-tissue regeneration and rapid tumor recurrence post-resection are critical challenges in osteosarcoma and other bone cancers. Conventional bone tissue engineering scaffolds lack inhibitory effects on bone tumor recurrence. Herein, multifunctional scaffolds (named DOX/PDA@CDHA) were designed through the spontaneous polymerization of Dopamine (PDA) on the surface of Calcium Deficient Hydroxyapatite (CDHA) scaffolds, followed by in situ loading of the chemotherapeutic drug Doxorubicin (DOX). The PDA coating endowed the scaffolds with significant photothermal properties, while the gradual release of DOX provided an effective chemotherapeutic effect. The on-demand release of DOX at tumor sites, triggered by dual stimulation (near-infrared (NIR) light and the acidic pH typical of tumor microenvironments), specifically targets cancer cells, thereby mitigating systemic side effects. These unique characteristics facilitated effective osteosarcoma eradication both in vitro and in vivo. Moreover, the scaffold's composition, which mimics the mineral phase of natural bone and is enhanced by PDA's biocompatibility, promotes critical osteogenic and angiogenic processes. This facilitates not only tumor eradication but also the regeneration of healthy bone tissue. Collectively, this study presents a potent candidate for the regeneration of bone defects induced by osteosarcoma.

Enhanced Drug Delivery with Oil-in-Water Nanoemulsions: Stability and Sustained Release of Doxorubicin.

In this study, oil-in-water nanoemulsions are prepared, an isotropic mixture of oil, surfactant, and cosurfactants. The nanoemulsions exhibit stable structures and are capable of efficiently encapsulating hydrophobic drugs such as doxorubicin (Dox). Compared to polymeric micelles, nanoemulsions demonstrate enhanced stability and loading capacity for Dox. Furthermore, nanoemulsions release Dox steadily over 14 days, with 51.6% released within the initial 24h and up to 80% over the subsequent period. These properties suggest that nanoemulsions can mitigate the side effects related to the burst release of Dox, thereby improving therapeutic efficacy and safety. Additionally, nanoemulsion-treated cardiomyocytes show increased viability compared to those treated with free Dox, indicating the potential of nanoemulsions to alleviate Dox-induced cardiotoxicity. Overall, nanoemulsions hold promise as versatile and efficient drug carriers for improving cancer treatment outcomes.

Biodegradable chitin nanofiber-alginate dialdehyde hydrogel: An injectable, self-healing scaffold for anti-tumor drug delivery

Injectable hydrogels fabricated from natural polymers have attracted increasing attentions for their potential in biomedical application owing to the biocompatibility and biodegradability. A new class of natural polymer based self-healing hydrogel is constructed through dynamic covalent bonds. The injectable self-healing hydrogels are fabricated by introducing alginate aldehyde to form Schiff base bonds with the chitin nanofibers. These hydrogels demonstrate excellent self-healing properties, injectability, and pH-responsive sol-gel transition behaviors. As a result, they can serve as carriers to allow an effective encapsulation of doxorubicin (DOX) for drug delivery. Furthermore, these hydrogels exhibit excellent biocompatibility and degradability in vitro and in vivo. The sustained release of DOX from the hydrogels effectively suppresses tumor growth in animal models without causing significant systemic toxicity, suggesting their potential application in anti-tumor therapies.

Nanoparticle-functionalized acrylic bone cement for local therapeutic delivery to spine metastases

Aim: Polymethylmethacrylate bone cement is often used to reconstruct critical-sized defects generated by the surgical resection of spinal metastases. Residual tumor cells after a resection can drive recurrence and destabilization. Doxorubicin (DOX) is a common chemotherapeutic drug with unwanted side-effects when administered systemically. Mesoporous silica nanoparticles (NPs) are gaining attention for targeted drug delivery to bypass the negative side effects associated with systemic drug administration. An NP-functionalized cement was developed for the local release of DOX and its ability to suppress cancer cells was tested. Methods: DOX was loaded onto NPs which were then mixed into the cement. Static contact angles were measured. Drug release profiles were obtained over a period of 4 weeks. Cement constructs were incubated with two-dimensional (2D) cultures of human bone-marrow derived mesenchymal stem cells and human osteoblasts, as well as 2D and three-dimensional (3D) cultures of breast and prostate cancer cell lines. Cell metabolic activity and viability were evaluated. Cell migration and spheroid growth of cancer cell lines were assessed in collagen-coated spheroid cultures. Results: NPs were homogenously dispersed and did not alter the mechanical strength nor the wettability of the cement. A sustained DOX release profile was achieved with the addition of NPs to the bone cement. The release profile of DOX from NP cement may be modified by varying the amount of the drug loaded onto the NPs and the proportion of NPs in the cement. Cancer cells treated with the cement constructs showed a dose- and time-dependent inhibition, with minimal toxicity against healthy cells. Cancer cell migration and spheroid growth were impaired in 3D culture. Conclusions: NPs were shown to be essential for sustained DOX release from bone cement. DOX-loaded NP cement can inhibit cancer cells and impair their migration, with strong potential for in vivo translation studies.

Coiled-Coil Protein Hydrogels Engineered with Minimized Fiber Diameters for Sustained Release of Doxorubicin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks expressed protein targets, making therapy development challenging. Hydrogels offer a promising new route in this regard by improving the chemotherapeutic efficacy through increased solubility and sustained release. Moreover, subcutaneous hydrogel administration reduces patient burden by requiring less therapy and shorter treatment times. We recently established the design principles for the supramolecular assembly of single-domain coiled-coils into hydrogels. Using a modified computational design algorithm, we designed Q8, a hydrogel with rapid assembly for faster therapeutic hydrogel preparation. Q8 encapsulates and releases doxorubicin (Dox), enabling localized sustained release via subcutaneous injection. Remarkably, a single subcutaneous injection of Dox-laden Q8 (Q8•Dox) significantly suppresses tumors within just 1 week. This work showcases the bottom-up engineering of a fully protein-based drug delivery vehicle for improved TBNC treatment via noninvasive localized therapy.

Zwitterionic functionalization of polysaccharide gum by graft copolymerization to develop 3-D network materials for anticancer drug delivery applications

Herein, functionalization of polysaccharide gum has been carried out to develop network copolymeric materials for use in sustained anticancer drug delivery. Grafting reaction of poly[2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSAH) onto sterculia gum has been done in the presence of crosslinker. Copolymeric materials were characterized by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 13C-nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). SEM, AFM and XRD displayed heterogeneous morphology with a rough surfaces of amorphous copolymeric materials. Peaks at 173.822 ppm (carbonyl carbon) and at 60.653 ppm (methylene carbon attached to a quaternary ammonium group) confirmed the addition of poly(MEDSAH) during the grafting reaction. Mesh size in network hydrogel was found between 14.54 nm to 36.32 nm. Sustained release of doxorubicin was found with non-Fickian diffusion and was best demonstrated by the kinetic model Hixson Crowell. The biocompatibility of material was revealed in a haemolytic index (1.74 ± 0.26%) less than two percent during the copolymer-blood interaction. The material exhibited antioxidant and mucoadhesion properties. Free radical scavenging ability of copolymers was 49.41 ± 0.97% in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay of the antioxidant test. These properties of copolymeric hydrogels demonstrated their suitability for use in sustained drug delivery systems for cancer chemotherapy.

A co-assembly process for high strength and injectable dual network gels with sustained doxorubicin release performance.

Adopting a non-covalent co-assembly strategy shows great potential in loading drugs efficiently and safely in drug delivery systems. However, finding an efficient method for developing high strength gels with thixotropic characteristics is still challenging. In this work, by hybridizing the low molecular weight gelator fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-F) (first single network, 1st SN) and alginate (second single network, 2nd SN) into a dual network (DN) gel, gels with high strength as well as thixotropy were prepared efficiently. The DN gels showed high strength (103 Pa in SN gels and 105 Pa in DN gels) and thixotropic characteristics (yield strain <25%; recovery ratio >85% within 100 seconds). The application performance was verified by loading doxorubicin (DOX), showing better encapsulation capacity (77.06% in 1st SN, 59.11% in 2nd SN and 96.71% in DN) and sustained release performance (lasting one week under physiological conditions) than single network gels. Experimental and DFT results allowed the elaboration of the specific non-covalent co-assembly mechanism for DN gel formation and DOX loading. The DN gels were formed by co-assembly driven by H-bond and π-π stacking interactions and then strengthened by Ca2+-coupling. Most DOX molecules co-assembled with Fmoc-F and alginate through π-π stacking and H-bond interactions (DOX-I), with a few free DOX molecules (DOX-II) left. Proven by the release dynamics test, DOX was released through a diffusion-erosion process, in an order of DOX-I first and then DOX-II. This work suggests that non-covalent co-assembly is a useful technique for effective material strengthening and drug delivery.

Incorporation of doxorubicin and CoFe2O4 nanoparticles into the cellulose acetate phthalate / polyvinyl alcohol (core)/ polyurethane (shell) nanofibers against A549 human lung cancer during chemotherapy/hyperthermia combined method

Cellulose acetate phthalate (CAP)/polyvinyl alcohol (PVA)/polyurethane (PU) nanofibers were synthesized by simple and coaxial electrospinning (ES) processes. Doxorubicin (DOX) and the CoFe2O4 nanoparticles were loaded into the nanofibers. The performance of the prepared nanofibers was investigated for the sustained release of DOX against A541 lung cancer cells under chemotherapy/external magnetic field (EMF) and alternating magnetic field (AMF, hyperthermia treatment) combined methods in both the in vitro and in vivo conditions. The sustained release of DOX from core-shell nanofibers containing 5 wt% cobalt ferrite was obtained within 300, 600 h, at pH of 5.5 and 7.4 without AMF and 168, 360 h, under an alternating magnetic field (AMF). More than 98.3 ± 0.2 % of A549 cancer cells were killed in the presence of core–shell nanofibers containing 100 μg DOX and 5 % cobalt ferrite nanoparticles in the presence of AMF. The flowcytometric results indicated that only 19.1 and 8.85 % cancer cells remained alive under EMF and AMF, respectively. The in vivo results revealed in stopping the growth of tumor volume and decrease in the relative tumor volume up to 0.5 were obtained using magnetic core–shell nanofibers containing 100 μg DOX and 5 % cobalt ferrite nanoparticles in the presence of EMF and AMF, respectively.

Development of a Cu/ZnO@ZIF-8 nanocomposite as a pH-responsive drug delivery vehicle for the sustained release of doxorubicin in human lung cancer cell lines

Nowadays the targeted drug release from a stable and non-toxic drug delivery vehicle is an onerous task. In this work, we developed a ZIF-8 based nanocomposite by the incorporation of copper doped zinc oxide nanoparticles onto the ZIF-8 frameworks. The formation of the composite was confirmed with the help of various spectral analyses such as FTIR, UV–visible, PXRD, XPS, TEM, SEM-EDS, TG/DTG, BET, and photoluminescent spectroscopy. The feasibility of the material as a drug delivery vehicle was analyzed by loading doxorubicin (DOX) and monitoring its release in human lung cancer cell line A549 under different pH conditions such as 1.2, 5.5, and 7.4. The release kinetics is in good agreement with the Higuchi model with a regression coefficient of 0.9999. The composite possesses a better drug loading capacity of 43.2 % and follows a sustained release kinetics at pH 5.5. The biocompatibility of the material is also noticed by monitoring the in vitro cytotoxicity and anticancer activity through MTT assay. The composite material shows a cytotoxicity of 71.99 % against human lung cancer cell line A549 and cell viability of 37 % towards the normal fibroblast cell line L929 at 100 μg/mL. The anticancer activity of the composite loaded with DOX was compared with the pure DOX. The results showed that the composite loaded with DOX shows better anticancer activity than that of pure DOX with an IC50 of 69.89 μg/mL, lower than that of pure DOX (85.52 μg/mL). The combined effect such as better drug loading, sustained and pH-responsive release and potential anticancer activity leads to the conclusion that the ZIF-8 based nanocomposite can be used as a better therapeutic agent against human lung cancer cell line A549.

Flower-shaped covalent organic framework synthesis and its anticancer drug delivery application

Fabrication of covalent organic frameworks (COFs) at room temperature is necessary due to their easy preparation, practical scale-up, and low cost to overcome the limitations of solvothermal and high-temperature synthesis. Herein, we fabricated flower-shaped COFs (FSCOFs) that were synthesized in various ratios of ortho-xylene and butanol mixture solvents. The FSCOFs exhibited excellent crystallinity with a pore size of approximately 10 nm, which was confirmed by PXRD and BET measurements. To utilize the FSCOFs as a drug carrier, doxorubicin (DOX) was loaded, followed by encapsulation of hyaluronic acid to increase the colloidal stability of FSCOFs in a physiological environment (FSCOFs-DOX-HA). The encapsulation efficiency and the drug loading capacity of FSCOFs-DOX-HA were 21.23 % and 29.82 %, respectively. Moreover, 92 % and 59 % of DOX is released in acidic environments and elevated GSH environments, proving the sensitivity of the FSCOFs as carriers. The excellent drug release mechanism of FSCOFs-HA-DOX is demonstrated by FSCOFs imine nitrogen protonation under acidic environment confirmed by its zeta potential changes under various physiological environments. The designed FSCOFs-DOX-HA was demonstrated to be a pH-sensitive drug carrier to deliver anticancer drugs into cancer cells. The MTT and drug internalization data demonstrated sustained DOX release from FSCOFs-DOX-HA. Finally, the real-time fluorescence demonstrates the effectiveness of the FSCOFs-DOX-HA upon cellular uptake and release of the anticancer drug. Thus, the FSCOFs system reported here opens a new path in COF research for drug carrier systems.

CD44 tagged hyaluronic acid - chitosan liposome carrier for the delivery of berberine and doxorubicin into lung cancer cells

Liposomes are unique biomolecular, capable of loading both hydrophilic and hydrophobic molecules and delivered into the biological system. Liposomes (L) coated with hyaluronic acid (HA) and chitosan (CS) carrier system was fabricated. Berberine (BER) and doxorubicin (DOX) were encapsulated to enhance drug proliferation and therapeutic effect in lung cancer cells. The FTIR, XRD, SEM, and TEM techniques were carried out for functional group identification, crystallinity, and surface morphology analysis, respectively. In-vitro drug release confirms the sustained release of BER and DOX in various physiological environments. HA-CS@BER&DOX-L has good penetration ability and higher cytotoxicity effect in the A549 cells, and the IC50 value of HA-CS@BER&DOX-L is 89.19 μg/300 μL. The pure liposome showed a negligible cytotoxicity effect, and the HA-CS@BER&DOX-L could efficiently induce the apoptosis of A549 cells. The cellular uptake analysis of the HA-CS@BER&DOX-L effectively targeted and entered the A549 cells and clearly observed C. elegans images. Hence, the proposed system will be a potential treatment methodology to enhance the cytotoxicity of the A549 cancer cells and be useful to future drug administration methodology development.

Sustained Release of Doxorubicin through Semi-Interpenetrating Polymer Network-Stabilized Micelles

Sustained Release of Doxorubicin through Semi-Interpenetrating Polymer Network-Stabilized Micelles

Temperature and pH-responsive PNIPAM@PAA Nanospheres with a Core-Shell Structure for Controlled Release of Doxorubicin in Breast Cancer Treatment

Stimuli-responsive polymers have been of great interest in the fabrication of advanced drug delivery systems. In this study, a facile approach was developed to synthesize a dually temperature/pH-responsive drug delivery system with a core-shell structure to control the release of doxorubicin (DOX) at the target site. For this purpose, poly(acrylic acid) (PAA) nanospheres were first synthesized using the precipitation polymerization technique and were used as pH-responsive polymeric cores. Then, poly(N-isopropylacrylamide) (PNIPAM) with thermo-responsivity properties was coated on the outer surface of PAA cores via seed emulsion polymerization technique to render monodisperse PNIPAM-coated PAA (PNIPAM@PAA) nanospheres. The optimized PNIPAM@PAA nanospheres with an average particle size of 116.8 nm (PDI= 0.243), had a high negative surface charge (zeta potential= -47.6 mV). Then, DOX was loaded on PNIPAM@PAA nanospheres and the entrapment efficiency (EE) and drug loading (DL) capacity were measured to be 92.7% and 18.5%, respectively. The drug-loaded nanospheres exhibited a low leakage at neutral pH and physiological temperature, but drug release significantly enhanced at acidic pH (pH= 5.5), indicating the tumor-environment responsive drug release behavior of the prepared nanospheres. Also, kinetics studies showed that, the sustained release of DOX from PNIPAM@PAA nanospheres was consistent with the Fickian diffusion mechanism. Moreover, the anticancer efficacy of DOX-loaded nanospheres was evaluated in vitro against MCF-7 breast cancer cells. The obtained results revealed that, the incorporation of DOX into PNIPAM@PAA nanospheres increases its cytotoxicity against cancer cells compared to the free DOX. Our results suggest that, PNIPAM@PAA nanospheres can be considered as a promising vector to release anticancer drugs with dual-stimuli responsivity to pH and temperature.

Construction of cyclodextrin microporous organic network based drug delivery platform for controllable release and targeting delivery of doxorubicin

Rational design and fabrication of effective drug delivery systems (DDS) are crucial for improving the therapeutic effectiveness and overcoming the shortcomings of chemotherapy. Herein, we report the construction of a novel cyclodextrin microporous organic network (CD-MON)-based DDS via a convenient thiol‑yne click reaction and dehydration condensation modification for the controllable release and targeted delivery of doxorubicin (DOX), a typical chemotherapy drug. The constructed DDS afforded multiple hydrophobic, hydrogen-bonding, and host-guest interaction sites, allowing for the efficient loading of DOX. The obtained DDS also exhibited good sustained and long-term release of DOX. Additionally, the proposed DDS offers good biocompatibility and exhibits an obvious aggregation-induced emission. Furthermore, the introduction of folic acid (FA) into the CD-MON-based DDS provided excellent targeting capacity for FA receptor-positive NCI-H226 cells. This study proved the universality of the design, synthesis, and application of CD-MON-based DDS, revealing the great potential of CD-MONs in drug delivery.

Unimolecular Micelles from Randomly Grafted Arborescent Copolymers with Different Core Branching Densities: Encapsulation of Doxorubicin and In Vitro Release Study

A series of amphiphilic arborescent copolymers of generations G1 and G2 with an arborescent poly(γ-benzyl L-glutamate) (PBG) core and poly(ethylene oxide) (PEO) chain segments in the shell, PBG-g-PEO, were synthesized and evaluated as drug delivery nanocarriers. The PBG building blocks were generated by ring-opening polymerization of γ-benzyl L-glutamic acid N-carboxyanhydride (Glu-NCA) initiated with n-hexylamine. Partial or full deprotection of the benzyl ester groups followed by coupling with PBG chains yielded a comb-branched (arborescent polymer generation zero or G0) PBG structure. Additional cycles of deprotection and grafting provided G1 and G2 arborescent polypeptides. Side chains of poly(ethylene oxide) were then randomly grafted onto the arborescent PBG substrates to produce amphiphilic arborescent copolymers. Control over the branching density of G0PBG was investigated by varying the length and the deprotection level of the linear PBG substrates used in their synthesis. Three G0PBG cores with different branching densities, varying from a compact and dense to a loose and more porous structure, were thus synthesized. These amphiphilic copolymers behaved similar to unimolecular micelles in aqueous solutions, with a unimodal number- and volume-weighted size distributions in dynamic light scattering measurements. It was demonstrated that these biocompatible copolymers can encapsulate hydrophobic drugs such as doxorubicin (DOX) within their hydrophobic core with drug loading efficiencies of 42-65%. Sustained and pH-responsive DOX release was observed from the unimolecular micelles, which suggests that they could be useful as drug nanocarriers for cancer therapy.

Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs

In this study, novel Trojan particles were engineered for direct delivery of doxorubicin (DOX) and miR-34a as model drugs to the lungs to raise local drug concentration, decrease pulmonary clearance, increase lung drug deposition, reduce systemic side effects, and overcome multi-drug resistance. For this purpose, targeted polyelectrolyte nanoparticles (tPENs) developed with layer-by-layer polymers (i.e., chitosan, dextran sulfate, and mannose-g-polyethyleneimine) were spray dried into a multiple-excipient (i.e., chitosan, leucine, and mannitol). The resulting nanoparticles were first characterized in terms of size, morphology, in vitro DOX release, cellular internalization, and in vitro cytotoxicity. tPENs showed comparable cellular uptake levels to PENs in A549 cells and no significant cytotoxicity on their metabolic activity. Co-loaded DOX/miR-34a showed a greater cytotoxicity effect than DOX-loaded tPENs and free drugs, which was confirmed by Actin staining. Thereafter, nano-in-microparticles were studied through size, morphology, aerosolization efficiency, residual moisture content, and in vitro DOX release. It was demonstrated that tPENs were successfully incorporated into microspheres with adequate emitted dose and fine particle fraction but low mass median aerodynamic diameter for deposition into the deep lung. The dry powder formulations also demonstrated a sustained DOX release at both pH values of 6.8 and 7.4.

Nanocomplexes of doxorubicin and DNA fragments for efficient and safe cancer chemotherapy.

Cancer-targeted therapy by a chemotherapeutic agent formulated in a nanoscale platform has been challenged by complex and inefficient manufacturing, low drug loading, difficult characterization, and marginally improved therapeutic efficacy. This study investigated facile-to-produce nanocomplexes of doxorubicin (DOX), a widely used cancer drug, and clinically approved DNA fragments that are extracted from a natural source. DOX was found to self-assemble DNA fragments into relatively monodispersed nanocomplexes with a diameter of ∼70nm at 14.3% (w/w) drug loading by simple and scalable mixing. The resulting DOX/DNA nanocomplexes showed sustained DOX release, unlike overly stable Doxil®, cellular uptake via multiple endocytosis pathways, and high hematological and immunological compatibility. DOX/DNA nanocomplexes eradicated EL4 T lymphoma cells in a time-dependent manner, eventually surpassing free DOX. Extended circulation of DOX/DNA nanocomplexes, while avoiding off-target accumulation in the lung and being cleared from the liver, resulted in rapid accumulation in tumor and lowered cardio toxicity. Finally, tumor growth of EL4-challenged C57BL/6 mice (syngeneic model) and OPM2-challenged NSG mice (human xenograft model) were efficiently inhibited by DOX/DNA nanocomplexes with enhanced overall survival, in comparison with free DOX and Doxil®, especially upon repeated administrations. DOX/DNA nanocomplexes are a promising chemotherapeutics delivery platform for their ease of manufacturing, high biocompatibility, desired drug release and accumulation, efficient tumor eradication with improved safety, and further engineering versatility for extended therapeutic applications.

Metal-organic-framework-based pyroptosis nanotuner with long blood circulation for augmented chemotherapy.

Pyroptosis is a proinflammatory form of cell death mediated by members of the gasdermin family, and is a powerful tool against cancer. Herein, a pH-responsive doxorubicin (DOX)-encapsulating zeolitic imidazolate framework-8 (ZIF-8) nanoparticle coated with a carboxybetaine-based zwitterionic polymer (DOX@ZIF-8@PCBMA) was prepared. Furthermore, decitabine (DAC) was loaded to obtain a pyroptosis nanotuner (DOX@ZIF-8@PCBMA-DAC). This nanotuner displayed extended blood circulation and enhanced tumor accumulation. In addition, the ZIF-8 structure and disulfide-crosslinked PCBMA coating endowed DOX@ZIF-8@PCBMA-DAC with acidic-pH- and glutathione-responsive degradation. The nanotuner could robustly activate caspase-3 to induce gasdermin E (GSDME)-dependent pyroptosis via the sustained release of DAC and DOX, contributing to excellent tumor suppression with negligible side effects, which may provide novel insights into traditional chemotherapy.

Switching the Mode of Drug Release from a Reaction-Coupled Low-Molecular-Weight Gelator System by Altering Its Reaction Pathway.

Low-molecular-weight hydrogels are attractive scaffolds for drug delivery applications because of their modular and facile preparation starting from inexpensive molecular components. The molecular design of the hydrogelator results in a commitment to a particular release strategy, where either noncovalent or covalent bonding of the drug molecule dictates its rate and mechanism. Herein, we demonstrate an alternative approach using a reaction-coupled gelator to tune drug release in a facile and user-defined manner by altering the reaction pathway of the low-molecular-weight gelator (LMWG) and drug components through an acylhydrazone-bond-forming reaction. We show that an off-the-shelf drug with a reactive handle, doxorubicin, can be covalently bound to the gelator through its ketone moiety when the addition of the aldehyde component is delayed from 0 to 24 h, or noncovalently bound with its addition at 0 h. We also examine the use of an l-histidine methyl ester catalyst to prepare the drug-loaded hydrogels under physiological conditions. Fitting of the drug release profiles with the Korsmeyer-Peppas model corroborates a switch in the mode of release consistent with the reaction pathway taken: increased covalent ligation drives a transition from a Fickian to a semi-Fickian mode in the second stage of release with a decreased rate. Sustained release of doxorubicin from the reaction-coupled hydrogel is further confirmed in an MTT toxicity assay with MCF-7 breast cancer cells. We demonstrate the modularity and ease of the reaction-coupled approach to prepare drug-loaded self-assembled hydrogels in situ with tunable mechanics and drug release profiles that may find eventual applications in macroscale drug delivery.

Extended-release of doxorubicin through green surface modification of gold nanoparticles: in vitro and in ovo assessment

In the present study, a green surface modification of gold nanoparticles (GNPs) using chondroitin sulfate (CHS) and chitosan (CS) to deliver an extended-release of doxorubicin (DOX) was proposed. Following synthesis of each step of unconjugated counterpart, including CHS-GNPs, DOX–CHS–GNP, and conjugated construct DOX–CHS–GNP-CS, physicochemical properties of the nanoparticles (NPs) were characterized by FT-IR, DLS, and TEM analyses, and the release of DOX was determined by using UV–Vis spectrometry. Then, NPs were effectively taken up by MDA-MB-468, βTC-3, and human fibroblast (HFb) cell lines with high release percent and without significant cytotoxicity. The DOX–CHS–GNPs and DOX–CHS–GNP-CS NPs showed a mean size of 175.8 ± 1.94 and 208.9 ± 2.08 nm; furthermore, a zeta potential of − 34 ± 5.6 and − 25.7 ± 5.9 mV, respectively. The highest release of DOX was 73.37% after 45 h, while in the absence of CS, the release of DOX was 76.05% for 24 h. Compared to CHS-GNPs, the presence of CS decreased the rate of sustained release of DOX and improved the drug release efficiency. The results demonstrated an excellent release and negligible cytotoxicity at high concentrations of CHS-GNP-CS. Consequently, in ovo assessment corroborated the efficacy of the green fabricated NPs proposed effective targeted delivery of DOX for anti-tumor therapy in vitro.Graphical