Potential Sustained Release Research Articles

Sodium Alginate/Poly (Acrylicacid) Hydrogel Composite, Potential Carrier for Fibroblast Growth Factor1 (FGF1) Delivery.

Fibroblast growth factor1 is a powerful signaling molecule that plays a critical role in injury repair of diverse tissue by stimulating cell growth and angiogenesis. FGF1 has significant role in the cell fate and regulating inflammation with short half-life and poor in vivo stability. The encapsulation of the growth factor in the hydrogel led to peptide protect from the degradation and/or immune recognition and enable controlled drug delivery over a longer period of time. The aim of this study is to develop and evaluate a hydrogel carrier with adjustable release rate while maintaining bioactivity of FGF1. Here we describe an optimal ratio of sodium alginate and polyacrylic acid without additional cross linker containing optimum amount of FGF1 with the potential of sustained release to be used as a therapeutic agent. The carrier was characterized by FTIR, contact angle and swelling ratio. The activity of FGF1 after release from the hydrogel was confirmed by ELISA and Western blot. Further assessment of genes related to inflammation were evaluated by RTPCR. This hydrogel is able to deliver growth factors by restricting the essential proteins within the matrix to prevent rapid proteolysis and explosive release and is therefore widely applicable.

Molecularly Imprinted Polymeric Nanoparticles as Drug Delivery System for Tenofovir, an Acyclic Nucleoside Phosphonate Antiviral.

A molecularly imprinted polymer of Tenofovir (1), an FDA-approved acyclic nucleoside phosphonate with antiviral activity, was synthesized using a non-covalent approach. A pre-polymerization complex was formed between (1) and DMAEMA and in-house synthetic N1-[(2-methacryloyloxy)ethyl] thymine, with EGDMA as a cross-linker in an MeCN/H2O (9:1, 1:1) mixture as a porogen, giving an imprinting factor (IF) of 5.5 at 2.10-5 mol/L. Binding parameters were determined by the Freundlich-Langmuir model, Qmax and Ka, and well as the particle morphology for MIP and NIP. Finally, the release profiles, for MIP and NIP, were obtained at 25 °C and 37 °C, which is body temperature, in a phosphate buffer saline, pH 7.4, mimicking the blood pH value, to determine the potential sustained release of our polymeric materials.

PH responsive THPS crosslinked injectable hydrogel with Cu-metformin sustained-release for accelerating wound healing

The utilitarian capacity of hydrogels in fostering a conducive milieu for cellular viability renders them a compelling alternative to conventional wound dressings. Nonetheless, the uncontrolled drug release exhibited by numerous drug-loaded hydrogel dressings often undermines their capacity for sustaining therapeutic efficacy over prolonged periods, while certain hydrogel formulations prove inadequate for addressing deep-seated wounds with low pH caused by chronic bacterial infections. Within the scope of this investigation, a novel pH-responsive injectable sustained-release hydrogel is developed through the crosslinking of tetrakis (hydroxymethyl) phosphonium sulfate (THPS) with carboxymethyl chitosan (CMCS) and Ɛ-poly-L-lysine (EPL). This innovative hydrogel manifests rapid gelation within a span of 30 s sans the requirement of a catalyst, alongside demonstrating commendable antibacterial attributes facilitated by the incorporation of a Cu-metformin complex (CuMet). Furthermore, the lyophilized hydrogel exhibits exceptional water absorbency and hemostatic qualities, effectively addressing exudative concerns and mitigating blood loss. In vitro assessments ascertain the higher drug release under acidic conditions and sustained drug release potential of CMCS/EPL/CuMet for up to 120 h, concomitantly expediting wound healing processes through the attenuation of bacterial colonization and inflammatory responses. In summation, this investigation furnishes novel insights into the viability of the developed formulation as a sustained-release injectable wound dressing.

Design, fabrication, and evaluation of keratin and pectin incorporated supramolecular structured zero-oxidation state selenium nanogel blended 3D printed transdermal patch

This study investigates the synthesis of selenium nanoparticles (SeNPs), owing to the low cost and abundance of selenium. However, the toxicity of SeNP prompts the development of a selenium nanocomposite (SeNC) containing pectin, keratin, and ferulic acid to improve the bioactivity of Se[0]. Further, incorporating the SeNC in a suitable formulation for drug delivery as a transdermal patch was worth studying. Accordingly, various analytical techniques were used to characterize the SeNPs and the SeNC, confirming successful synthesis and encapsulation. The SeNC exhibited notable particle size of 448.2 ± 50.2 nm, high encapsulation efficiency (98.90 % ± 2.4 %), 28.1 ± 0.45 drug loading, and sustained drug release at pH 5.5. Zeta potential and XPS confirmed the zero-oxidation state. The supramolecular structure was evident from spectral analysis endorsing the semi-crystalline nature of the SeNC and SEM images showcasing flower-shaped structures. Further, the SeNC demonstrated sustained drug release (approx. 22 % at 48 h) and wound-healing potential in L929 fibroblast cells. Subsequently, the SeNC loaded into a gelling agent exhibited shear thinning properties and improved drug release by nearly 58 %. A 3D printed reservoir-type transdermal patch was developed utilizing the SeNC-loaded gel, surpassing commercially available patches in characteristics such as % moisture uptake, tensile strength, and hydrophobicity. The patch, evaluated through permeation studies and CAM assay, exhibited controlled drug release and angiogenic properties for enhanced wound healing. The study concludes that this patch can serve as a smart dressing with tailored functionality for different wound stages, offering a promising novel drug delivery system for wound healing.

Development and characterization of liposomal formulations containing sesquiterpene lactones for the treatment of chronic gout

Gout and hyperuricemia are characterized by high uric acid levels, and their treatment involves medications that have adverse effects. In this study, we evaluated oral liposomal formulations with eremantholide C and goyazensolide as a novel approach to reduce the toxicity associated with these substances while maintaining their anti-hyperuricemic activity. We characterized the formulations and evaluated them based on encapsulation efficiency and stability over 12 months and under simulated physiological environments. We determined the toxicity of the liposomal formulations in Caco-2 cells and the anti-hyperuricemic activity in rats. The formulations exhibited nanometric size, a narrow size distribution, and a negative zeta potential, indicating their stability and uniformity. The efficient encapsulation of the sesquiterpene lactones within the liposomes emphasizes their potential for sustained release and therapeutic efficacy. Stability evaluation revealed a small decrease in the eremantholide C concentration and a remarkable stability in the goyazensolide concentration. In Caco-2 cells, the liposomes did not exert toxicity, but did exhibit an antiproliferative effect. In vivo assays demonstrated that the liposomes reduced serum uric acid levels. Our study represents an advancement in gout and hyperuricemia treatment. The liposomal formulations effectively reduced the toxicity associated with the sesquiterpene lactones while maintaining their therapeutic effects.

Enhancing the solubility and dose delivery of drospirenone through oxidized regenerated cellulose hydrogel compound with liposome system

At present, contraceptive drugs such as Drospirenone (DROP) encounter challenges stemming from their abbreviated half-life and constrained efficacy. Therefore, the imperative arises to formulate innovative strategies that not only prolong the duration of action but also enhance the overall effectiveness of these drugs. This study introduces a two-step delivery system designed to overcome the limitations associated with DROP applications. Initially, a Drospirenone liposome (LIP/DROP) complex was meticulously prepared. Subsequently, this complex was immobilized within a cellulose-based hydrogel, constructed from aldehyde-replaced oxidized regenerated cellulose (AC) and chitosan (CS), employing Schiff base reaction crosslinking. The encapsulation efficiency achieved an impressive 84.9% (±0.73), accompanied by an 878-fold increase in solubility. Notably, each 0.35 g of the hydrogel demonstrated the capacity to load 96.48 mg of DROP. TEM was used to observe the particle size and morphology of LIP/DROP. SEM and FTIR were employed to investigate the structure and surface morphology of the prepared hydrogel and AC. The properties of the hydrogel related to the application of drug delivery, including swelling, mechanical, bacterial inhibition, and cytotoxicity were meticulously investigated. Moreover, the drug release rate of the prepared LIP hydrogel was assessed over 400 h (9%–40%), demonstrating its potential for sustained release of DROP. These improvements in solubility and stability offer promise for expanding the utilization of DROP in contraceptive applications.

Hydrolysis and Transport Characteristics of Phospholipid Complex of Alkyl Gallates: Potential Sustained Release of Alkyl Gallate and Gallic Acid.

Phospholipid complexes of alkyl gallates (A-GAs) including ethyl gallate (EG), propyl gallate (PG), and butyl gallate (BG) were successfully prepared by the thin film dispersion method. HPLC-UV analysis in an everted rat gut sac model indicated that A-GAs can be liberated from phospholipid complexes, which were further hydrolyzed by intestinal lipase to generate free gallic acid (GA). Both A-GAs and GA are able to cross the membrane, and the hydrolysis rate of A-GAs and the transport rate of GA are positively correlated with the alkyl chain length. Especially, compared with the corresponding physical mixtures, the phospholipid complexes exhibit slower sustained-release of A-GAs and GA. Therefore, the formation of phospholipid complexes is an effective approach to prolong the residence time in vivo and additionally enhance the bioactivities of A-GAs and GA. More importantly, through regulating the carbon skeleton lengths, controlled-release of alkyl gallates and gallic acid from phospholipid complexes will be achieved.

A superporous and pH-sensitive hydrogel from Salvia hispanica (chia) seeds: stimuli responsiveness, on-off switching, and pharmaceutical applications.

The use of plant seed-based hydrogels to design drug delivery systems (DDSs) has increased due to their swellable, pH-responsive, biocompatible, biodegradable, and non-toxic nature. Herein, the chia seeds hydrogel (CSH) was extracted through an aqueous extraction method to explore its pH and salt-responsive swelling behavior and sustained release potential. The CSH was characterized using Fourier transform infrared (FT-IR) and solid-state cross-polarization magic angle spinning carbon-13 nuclear magnetic resonance (solid/state CP-MAS 13C/NMR) spectra. Thermal analysis indicated that the CSH is a thermally stable material and decomposes in two steps. The scanning electron microscope (SEM) images of CSH witnessed the existence of microscopic channeling and a superporous nature with average pore sizes of 18 ± 11 μm (transverse cross-sections) and 23 ± 15 μm (longitudinal cross-sections). The CSH is a haemocompatible material. The CSH revealed pH and saline-responsive swelling in powder and compressed form (tablet) in the following order; distilled water (DW) > pH 7.4 > pH 6.8 > pH 1.2. Moreover, the swelling of CSH followed second-order kinetics. The swelling of CSH powder and tablets was decreased with increasing salt concentration. The pH, solvent, and saline responsive on/off switching (swelling/deswelling) results of the CSH and tablets disclosed its stimuli-responsive nature. The CSH prolonged the release of valsartan for 5 h at pH 7.4, whereas, negligible release (19.3%) was noted at pH 1.2. The valsartan release followed first-order kinetics and the non-Fickian diffusion. In conclusion, the CSH is a stimuli-responsive smart material with great potential to develop pH-sensitive and targeted DDSs.

Hydrogen therapy: recent advances and emerging materials.

Hydrogen therapy, leveraging its selective attenuation of hydroxyl radicals (˙OH) and ONOO-, has emerged as a pivotal pathophysiological modulator with antioxidant, anti-inflammatory, and antiapoptotic attributes. Hydrogen therapy has been extensively studied both preclinically and clinically, especially in diseases with an inflammatory nature. Despite the substantial progress, challenges persist in achieving high hydrogen concentrations in target lesions, especially in cancer treatment. A notable breakthrough lies in water/acid reactive materials, offering enhanced hydrogen generation and sustained release potential. However, limitations include hydrogen termination upon material depletion and reduced bioavailability at targeted lesions. To overcome these challenges, catalytic materials like photocatalytic and sonocatalytic materials have surfaced as promising solutions. With enhanced permeability and retention effects, these materials exhibit targeted delivery and sustained stimuli-reactive hydrogen release. The future of hydrogen therapy hinges on continuous exploration and modification of catalytic materials. Researchers are urged to prioritize improved catalytic efficiency, enhanced lesion targeting effects, and heightened biosafety and biocompatibility in future development.

A bio-ionic liquid based self-healable and adhesive ionic hydrogel for the on-demand transdermal delivery of a chemotherapeutic drug.

The non-invasive nature and potential for sustained release make transdermal drug administration an appealing treatment option for cancer therapy. However, the strong barrier of the stratum corneum (SC) poses a challenge for the penetration of hydrophilic chemotherapy drugs such as 5-fluorouracil (5-FU). Due to its biocompatibility and capacity to increase drug solubility and permeability, especially when paired with chemical enhancers, such as oleic acid (OA), which is used in this work, choline glycinate ([Cho][Gly]) has emerged as a potential substance for transdermal drug delivery. In this work, we examined the possibility of transdermal delivery of 5-FU for the treatment of breast cancer using an ionic hydrogel formulation consisting of [Cho][Gly] with OA. Small angle neutron scattering, rheological analysis, field emission scanning electron microscopy, and dynamic light scattering analysis were used to characterize the ionic hydrogel. The non-covalent interactions present between [Cho][Gly] and OA were investigated by computational simulations and FTIR spectroscopy methods. When subjected to in vitro drug permeation using goat skin in a Franz diffusion cell, the hydrogel demonstrated sustained release of 5-FU and effective permeability in the order: [Cho][Gly]-OA gel > [Cho][Gly] > PBS (control). The hydrogel also demonstrated 92% cell viability after 48 hours for the human keratinocyte cell line (HaCaT cells) as well as the normal human cell line L-132. The breast cancer cell line MCF-7 and the cervical cancer cell line HeLa were used to study in vitro cytotoxicity that was considerably affected by the 5-FU-loaded hydrogel. These results indicate the potential of the hydrogel as a transdermal drug delivery vehicle for the treatment of breast cancer.

Magnetic induction heating and drug release properties of magnetic carbon nanotubes

Aim The use of magnetic carbon nanotubes for multi-modal cancer treatment, incorporating both hyperthermia and drug delivery functions, has drawn substantial interest. Yet, the present method of regulating hyperthermia temperature involves manually adjusting the magnetic field intensity, adding to the complexity and difficulty of clinical applications. This study seeks to design novel magnetic carbon nanotubes capable of self-temperature regulation, and investigate their drug loading and release characteristics. Methods Using the co-precipitation method, we synthesized magnetic carbon nanotubes with a Curie temperature of 43 °C. A comprehensive investigation was conducted to analyze their morphology, crystal structure, and magnetic characteristics. To enhance their functionality, chitosan and sodium alginate modifications were introduced, enabling the loading of the antitumor drug doxorubicin hydrochloride (DOX) into these magnetic carbon nanotubes. Subsequently, the loading and release properties of DOX were investigated within the modified magnetic nanotubes. Results Under alternating magnetic field, magnetic carbon nanotubes exhibit self-regulating properties by undergoing a magnetic phase transition, maintaining temperatures around 43 °C as required for hyperthermia. On the other hand, during magnetic induction heating, the release percentage of DOX reached 23.5% within 2 h and 71.7% within 70 h at tumor pH conditions, indicating their potential for sustained drug release. Conclusions The prepared magnetic carbon nanotubes can effectively regulate the temperature during hyperthermia treatment while ensuring controlled drug release, which presents a promising method for preparing nanomaterials that synergistically enhance magnetic hyperthermia and chemotherapy drugs.

Development and Characterization of Terbinafine-Loaded Nanoemulgel for Effective Management of Dermatophytosis.

Dermatophytosis, the most prevalent fungal infection, is witnessing a rising incidence annually. To address this challenge, we developed a terbinafine-loaded oil-in-water nanoemulsion (TH-NE) through the aqueous microtitration method. The formulation comprised olive oil (oil phase), Span 80 (surfactant), and propylene glycol (co-surfactant). Pseudo-phase ternary diagrams and thermodynamic studies underscored the stability of TH-NE. Employing the Box-Behnken design (BBD), we optimized TH-NE, which resulted in a remarkable particle size of 28.07 nm ± 0.5, a low polydispersity index (PDI) of 0.1922 ± 0.1, and a substantial negative zeta potential of -41.87 mV ± 1. Subsequently, TH-NE was integrated into a 1.5% carbopol matrix, yielding a nanoemulgel (TH-NEG). Texture analysis of TH-NEG demonstrated a firmness of 168.00 g, a consistency of 229.81 g/s, negative cohesiveness (-83.36 g), and a work of cohesion at -107.02 g/s. In vitro drug release studies revealed an initial burst effect followed by sustained release, with TH-NEG achieving an impressive 88% release over 48 h, outperforming TH-NE (74%) and the marketed formulation (66%). Ex vivo release studies mirrored these results, with TH-NEG (86%) and TH-NE (71%) showcasing sustained drug release in comparison to the marketed formulation (67%). Confocal microscopy illustrated that TH-NEG and TH-NE penetrated to depths of 30 µm and 25 µm, respectively, into the epidermal layer. Furthermore, dermatokinetic studies highlighted the enhanced drug penetration of TH-NEG compared to TH-NE through mouse skin. In summary, our study establishes TH-NEG as a promising carrier for terbinafine in treating dermatophytosis, offering improved drug delivery and sustained release potential.

Chitosan-sodium percarbonate-based hydrogels with sustained oxygen release potential stimulated angiogenesis and accelerated wound healing.

The prolonged hypoxic conditions hinder chronic wounds from healing and lead to severe conditions such as delayed re-epithelialization and enhanced risk of infection. Multifunctional wound dressings are highly required to address the challenges of chronic wounds. Herein, we report polyurethane-coated sodium per carbonate-loaded chitosan hydrogel (CSPUO2 ) as a multifunctional dressing. The hydrogels (Control, CSPU, and CSPUO2 ) were prepared by freeze gelation method and the developed hydrogels showed high porosity, good absorption capacity, and adequate biodegradability. The release of oxygen from the CSPUO2 hydrogel was confirmed by the increase in pH and a sustained oxygen release was observed over the period of 21 days, due to polyurethane (CSPU) coating. The CSPUO2 hydrogel exhibited around 2-fold increased angiogenic potential in CAM assay when compared with Control and CSPU dressing. CSPUO2 also showed good level of antibacterial efficacy against E. coli and S. aureus. In a full-thickness rat wound model, CSPUO2 hydrogel considerably accelerated wound healing with exceptional re-epithelialization granulation tissue formation less inflammatory cells and improved skin architecture highlighting the tremendous therapeutic potential of this hydrogel when compared with control and CSPU to treat chronic diabetic and burn wounds.

PRO-DRUG NANOPARTICLES AS SYNERGISTIC DRUG COMBINATION CARRIERS FOR IDH1-WT GLIOBLASTOMA

Abstract AIMS Synergistic combinations of doxorubicin and gemcitabine have been assessed for post-surgical treatment of IDH1 wild-type glioblastoma (GBM). As a complementary drug carrier, hyperbranched and micellar nanoparticles are being investigated to enable enhanced drug loading and sustained drug release. METHOD 2D and 3D spheroid in vitro models have been generated from patient-derived glioblastoma cells resected from tumour core and invasive margin. Drug combinations were screened using synergy quantification from the Chou and Talalay method and synergy mechanisms investigated using measures of caspase 3/6-mediated apoptosis and γH2AX-mediated DNA damage. Polymeric nanoparticles (PEG-PCL) loaded with Cy5 were tested for internalisation and subsequent endocytosis pathway determination. Both single drug and drug combinations are currently being incorporated into PEG-PCL nanoparticles for in vitro assessment of biocompatibility, cellular uptake and cytotoxicity. RESULTS Data demonstrate synergism with doxorubicin and gemcitabine combinations is obtained in a molar ratio de- pendent manner. Consistent with this, enhanced apoptosis and DNA damage is observed in a synergistic manner. PEG-PCL nanoparticles demonstrate effcient cellular uptake and are internalised via dynamin-dependent caveolae and clathrin endocytotic pathways. Interestingly, nanoparticle internalisation is substantially in- creased (approx. 50%) in invasive GBM cells relative to proliferative core cells. CONCLUSIONS Doxorubicin and gemcitabine has been identified as a synergistic drug combination with the potential for sustained drug release when combined with PEG-PCL nanoparticle formulations. Together, the data has provided a platform of knowledge that will enable translation to pre-clinical in vivo models.

Isolation and Functioning Investigation of Salvia hispanica Seed Mucilage as A Potential Sustained Release Carrier for Water Soluble Drug

Isolation and Functioning Investigation of Salvia hispanica Seed Mucilage as A Potential Sustained Release Carrier for Water Soluble Drug

Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies

This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release agent for Verapamil HCl (BCS Class-I). Drug-loaded halloysite was prepared and tablet formulations were designed by varying amount of hydroxy propyl methyl cellulose (HPMC K4M). Physical characterization was carried out using SEM, FTIR, and DSC. Tabletability profiles were evaluated using USP1062 guidelines. Drug release kinetics were studied, and physiologically based pharmacokinetic (PBPK) modeling was performed. Compressed tablets possess satisfactory yield pressure of 625 MPa with adequate hardness and disintegration within 30 min. The initial release of the drug was due to surface drug on tablets, while the prolonged release at later time points (around 80 % drug release at 12 h) were due to halloysite loading. The FTIR spectra exhibited electrostatic attraction between the positively charged drug and the negatively charged Si-O-Si functional group of halloysite, while the thermogram showed Verapamil HCl melting point at ~146 °C with enthalpy change of −126.82 J/g. PBPK modeling exhibited PK parameters of optimized matrix formulation (VER-HNT3%) comparable to in vivo data. The study effectively demonstrated the potential of prepared biocomposite matrix as a commercially viable oral release modifying agent for highly soluble drugs.

Simvastatin-Loaded Nanostructured Lipid Carriers as Topical Drug Delivery System for Wound Healing Purposes: Preparation, Characterization, and In Vivo Histopathological Studies.

Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used drug to reduce total cholesterol and low-density lipoprotein (LDL) levels. Furthermore, several mechanisms showed the wound-healing potential of statins, especially simvastatin. Simvastatin is a lipophilic drug, therefore, it has low water solubility with limited skin permeability potential. In this regard, nanostructured lipid carriers (NLCs) were recruited as novel topical drug delivery systems to enhance skin adhesion and film formation, maintain skin integrity, sustain the release of simvastatin, and prolong simvastatin skin deposition to help pressure ulcers healing and regeneration. NLCs were fabricated using the solvent diffusion evaporation technique. Drug loading, in vitro drug release, and morphological assessment on the optimized formulation were considered. Furthermore, in vivo effect of simvastatin-loaded NLCs gel on pressure ulcer healing was assessed using a rat skin model. Histopathological assessments were compared with conventional simvastatin gel and drug-free NLCs gel. Simvastatin-loaded NLC with an average diameter of 100 nm was considered as the optimum formulation. According to the results entrapment efficiency of simvastatin within the NLCs was about 99.4%. Drug release studies revealed sustained drug release from NLCs in which about 87% of the drug was slowly released during 48 hours. Animal study results confirmed that simvastatin-loaded NLCs gel has better efficacy on pressure ulcers and could significantly reduce inflammation, and promote skin regeneration compared to both drug-free NLCs and conventional simvastatin gels. Simvastatin-loaded NLCs with an average particle size of 100 nm would be a promising novel topical drug delivery system with sustained drug release potential for pressure ulcer treatment.

Gastrointestinal Digestion and Microbial Hydrolysis of Alkyl Gallates: Potential Sustained Release of Gallic Acid

Phenolipids such as alkyl gallates (A-GAs) have been approved by the food industry as non-toxic antioxidant additives, which are also regarded as an emerging source of functional food ingredients. However, comprehensive understanding of their digestive absorption is needed. Thus, the models of live mice and anaerobic fermentation were used to clarify the distribution and microbial hydrolysis characteristics of A-GAs in the gastrointestinal tract. HPLC-UV results demonstrated that A-GAs could be hydrolyzed by intestinal lipases and gut microorganisms including Lactobacillus to produce free gallic acid (GA). Through regulating the chain length of the lipid part in A-GAs, the sustained and controllable release of the GA can be easily achieved. Furthermore, A-GAs were also able to reach the colon and the cecum, which would lead to potential gastrointestinal protective effects. Therefore, A-GAs may be applied as possible ingredient for functional foods.

ROS-Generating Poly(Ethylene Glycol)-Conjugated Fe3O4 Nanoparticles as Cancer-Targeting Sustained Release Carrier of Doxorubicin.

PurposeSite-specific drug delivery systems can contribute to the development and execution of effective cancer treatment. Due to its favorable features (including high biocompatibility, high hydrophilicity and ease of functionalization), poly(ethylene glycol) (PEG) has been widely adopted to design drug carriers. Generating carriers for delivery of hydrophobic anticancer agents, however, is still a challenge in carrier design.MethodsIn the first step, PEG is functionalized with dialdehyde to generate PEG-(CHO)2 using EDC/NHS chemistry. In the second step, Fe3O4 nanoparticles are functionalized with amino groups to generate Fe3O4-NH2. In the third step, PEG-(CHO)2, Fe3O4-NH2 and doxorubicin (DOX) react in an acidic environment to yield a drug conjugate (PEGDA-MN-DOX), which is subsequently characterized by FT-IR, 1H-NMR, SEM, TEM, DLS, TGA, and DSC.ResultsThe chemical functionalities of the drug conjugate are confirmed by FTIR, H-NMRand XRD analysis.The release pattern of PEGDA-MN-DOX is investigated at 25 and 37 °C at different pH values. The results indicate that the developed drug conjugate cannot only behave as a sustained-release carrier, but can also generate a significant level of reactive oxygen species (ROS), leading to a high level of toxicity against MCF-7 cells while still showing excellent biocompatibility in 3T3 cells.ConclusionThe reported conjugate shows anticancer potential, cancer-targeting ability, and ROS-generating capacity for effective drug encapsulation and sustained release in chemotherapy.

Osteogenic differentiation of adipose-derived stem cells on dihydroartemisinin electrospun nanofibers

BackgroundAdipose tissue-derived stem cells (ASCs) are promising candidate in stem cell therapies, and maintaining their stemness potential is vital to achieve effective treatment. Natural-based scaffolds have been recently attracted increasing attention in nanomedicine and drug delivery. In this study, Dihydroartemisinin (DHART)-loaded polycaprolactone collagen nanofibers (PCL/Col NFs) were constructed as effective biocompatible scaffolds through adjusting the proportions of hydrophobic/ hydrophilic polymers for enhanced osteoblastic differentiation of human adipose-derived stem cells (hADSCs).ResultsThe designed NFs were characterized through FTIR, XRD, TGA, FE-SEM, and tensile testing. DHART-loaded PCL/Col electrospun NFs provide an ideal solution, with the potential of sustained drug release as well as inhibition of drug re-crystallization. Interestingly, inhibiting DHART re-crystallization can improve its bioavailability and provide a more effective therapeutic efficacy. Besides, the data set found through FE-SEM, MTT, PicoGreen, qPCR, and alkaline phosphatase (ALP) assays revealed the improved adhesion and proliferation rate of hADSCs cultured on PCL/Col/DHART (5%) NFs after 14 and 21 days of incubation.ConclusionsThese findings confirmed the potential of the designed NF scaffolds for sustained/controlled release of DHART therapeutic molecules toward bone tissue regeneration and engineering.Graphical