Peppas-Sahlin Model Research Articles

Facile and green fabrication of algal protein/M(n+) hydrogel through coordination with cations for sustained release of vitamin B6

This study presents a facile method to prepare functional hydrogels based on spirulina algae protein/M(n+) and compares its properties with the conventional heat-induced method. Hence, algae protein isolate was extracted at the isoelectric point (pH 3.1) and hydrogels were synthesized through coordination with various cationic metals (Ca2+, Mg2+, Fe3+, Zn2+, and Cu2+) as a cross-linker. Morphological experiments (SEM) showed that the prepared hydrogels had a porous to dense and integrated structure depending on the type and concentration of metal cations. Fourier transform infrared (FTIR) spectra revealed the interaction of protein functional groups with coordinating metal ions. X-ray diffraction (XRD) patterns showed amorphous structures in algal protein/M(n+) hydrogels. The capacity of water absorption was strongly affected by pH and the type of metal cations and was much higher at pH 7.4 (490–801 %) than at acidic pH (pH 2.1, 212–419 %). The maximum release rate of vitamin B6 (83%) was obtained in Ca2+-hydrogels at pH 7.4 after 8 h. The Peppas-Sahlin model showed the best fit with the release profile of vitamin B6 (0.96–0.99), and it was also determined that the release process was based on Fickian diffusion (n ≤ 0.45) or anomalous transport (0.45 < n < 0.89). In conclusion, the study provided a new perspective on the fabrication of algal protein-based hydrogels, suggesting this matrix could be a novel delivery system for the controlled release of drugs/nutrients.

Microfiber-reinforced hydrogels prolong the release of human induced pluripotent stem cell-derived extracellular vesicles to promote endothelial migration

Extracellular vesicle (EV)-based approaches for promoting angiogenesis have shown promising results. Yet, further development is needed in vehicles that prolong EV exposure to target organs. Here, we hypothesized that microfiber-reinforced gelatin methacryloyl (GelMA) hydrogels could serve as sustained delivery platforms for human induced pluripotent stem cell (hiPSC)-derived EV. EV with 50–200 nm size and typical morphology were isolated from hiPSC-conditioned culture media and tested negative for common co-isolated contaminants. hiPSC-EV were then incorporated into GelMA hydrogels with or without a melt electrowritten reinforcing mesh. EV release was found to increase with GelMA concentration, as 12 % (w/v) GelMA hydrogels provided higher release rate and total release over 14 days in vitro, compared to lower hydrogel concentrations. Release profile modelling identified diffusion as a predominant release mechanism based on a Peppas-Sahlin model. To study the effect of reinforcement-dependent hydrogel mechanics on EV release, stress relaxation was assessed. Reinforcement with highly porous microfiber meshes delayed EV release by prolonging hydrogel stress relaxation and reducing the swelling ratio, thus decreasing the initial burst and overall extent of release. After release from photocrosslinked reinforced hydrogels, EV remained internalizable by human umbilical vein endothelial cells (HUVEC) over 14 days, and increased migration was observed in the first 4 h. EV and RNA cargo stability was investigated at physiological temperature in vitro, showing a sharp decrease in total RNA levels, but a stable level of endothelial migration-associated small noncoding RNAs over 14 days. Our data show that hydrogel formulation and microfiber reinforcement are superimposable approaches to modulate EV release from hydrogels, thus depicting fiber-reinforced GelMA hydrogels as tunable hiPSC-EV vehicles for controlled release systems that promote endothelial cell migration.

Folic acid conjugated poly (Amidoamine) dendrimer grafted magnetic chitosan as a smart drug delivery platform for doxorubicin: In-vitro drug release and cytotoxicity studies

This study reports the development of a magnetic and pH-responsive nanocarrier for targeted delivery and controlled release of doxorubicin (DOX). A multifunctional magnetic chitosan nanocomposite (FA–PAMAMG2–MCS) was fabricated by grafting poly(amidoamine) dendrimer and folic acid onto the MCS surface for active targeting. DOX was loaded into this core-shell bio-nanocomposite via adsorption. Structural and morphological characterization of the prepared nanomaterials was performed using XRD, FT-IR, VSM, TGA, BET, FE-SEM/EDX, and TEM techniques. Adsorption capacity of the FA–PAMAMG2–MCS was optimized by changing diverse parameters, such as pH, initial drug concentration, temperature, contact time, and adsorbent dosage. The maximum adsorption capacity for DOX was 102.85 mg g−1 at 298 K. The in-vitro drug release curve at pHs 5.6 and 7.4 manifested a faster drug release from the prepared nanocarrier in acidic environments and, conversely, a slower release in neutral environments over 48 h. The release kinetics followed Peppas-Sahlin models, showing non-Fickian behavior. Moreover, the in-vitro cytotoxicity studies against the human breast cancer (MDA-MB 231) cell line demonstrated the remarkable anticancer activity of the DOX@FA–PAMAMG2–MCS and declared its potency for nanomedicine applications. This multifunctional system could overcome limitations of conventional chemotherapeutic agents through pH-triggered drug release, enabling targeted cytotoxicity against cancer cells.

Kinetics Modelling of Vitamin B12 Release in an Agar/κ-Carrageenan Hydrogel Blend

A phycocolloidal hydrogel patch is studied as a potential material for the transdermal delivery device for vitamin B12. The vitamin release kinetics from an agar/κ-carrageenan hydrogel blend as a function of mass ratio and vitamin loading. Concentration measurements were done using a colorimetric method, and the experimental data were fitted into the Korsmeyer-Peppas model, Peppas-Sahlin model, and Berens-Hopfenberg model. From the curve fitting, parameters such as first-order polymer relaxation constant and diffusivity constant were obtained. The results showed that for the Korsmeyer-Peppas model and the Peppas-Sahlin model, the release mechanism followed Fickian diffusion predominantly. On the other hand, the Berens-Hopfenberg model fit shows that the release mechanism predominantly follows non-Fickian diffusion and may need to be modified.

Development of a potential carrageenan-based hard capsule as the alternative of conventional capsules by implementing the oligomerization reaction

Carrageenan-based (CRG) hard capsules have a slower disintegration rate compared to that of gelatin capsules. Therefore, there is an urgent need to optimize the performance of this material using the oligomerization process. The preparation was conducted by oligomerizing CRG, cross-linking it with maltodextrin (MD), and plasticizing it with sorbitol (SOR). Based on our research, we found that the capsule prepared with the code CRG(O)-MD/SOR had an ash content of 11.80% and a water content of 17.20 ± 1.20 %. No microbes or yeast were found in the capsule, and only negligible amounts of heavy metal traces were present. Scanning electron microscopy (SEM) morphology analysis of the capsule surface showed that no pores were observed, even at a magnification of 10,000 times. This result was supported by the BET-BJH analysis, which showed that the pores had an average diameter of 49.26 Ǻ. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the Tg of the prepared capsules was at 51.4 °C. Fourier-transform infrared spectroscopy (FTIR) analysis showed that the presence of citric acid as the oligomerization agent had changed the chain composition of the carrageenan. Acute toxicity analysis showed that the capsule was safe even at a dose of 3,000 mg/bw. The Young's modulus of CRG(O)-MD/SOR was determined to be 1.500 ± 0.52 MPa. In vitro disintegration testing of CRG(O)-MD/SOR showed that the capsule required 20.01 ± 1.13 mins, 23.13 ± 1.14 mins, and more than 120 mins to disintegrate at pH 1.2, 4.5, and 6.8, respectively. Release kinetics analyses showed that the drugs paracetamol (PCT) and salicylamide (SCA) followed the zeroth-order model at pH 1.2 and 4.5, while they were best described by the Peppas-Sahlin model at pH 6.8. Finally, the maximum swelling degree of the CRG(O)-MD/SOR hard capsule was determined to be 708.88%, which was reached in 15.22 mins. This capsule has the potential to be used as an alternative to conventional hard capsules on a broader scale. Furthermore, this work supports Sustainable Development Goals (SDGs) point 3, good health and well-being, by providing a capsule made from biomaterial.

Sodium alginate emulsion loaded with linalool: Preparation, characterization and antibacterial mechanism against Shigella sonnei

This study aimed to prepare sodium alginate-linalool emulsion (SA-LE) to overcome the low solubility of linalool and explore its inhibitory activity against Shigella sonnei. The results indicated that linalool significantly reduced the interfacial tension between SA and oil phase (p < 0.05). Droplet sizes of fresh emulsions were uniform with sizes from 2.54 to 2.58 μm. The ζ-potential was between −23.94 and -25.03 mV, and the viscosity distribution was 973.62 to 981.03 mPa·s at pH 5–8 (near neutral pH) without significant difference. In addition, linalool could be effectively released from SA-LE in accordance with the Peppas-Sahlin model, mainly described by Fickian diffusion. In particular, SA-LE can inhibit S. sonnei with a minimum inhibitory concentration of 3 mL/L, which was lower than free linalool. The mechanism can be described as damaging the membrane structure and inhibiting respiratory metabolism accompanied by oxidative stress based on FESEM, SDH activity, ATP and ROS content. These results suggest that SA is an effective encapsulation strategy to enhance the stability of linalool and its inhibitory effect on S. sonnei at near neutral pH. Moreover, the prepared SA-LE has the potential to be developed as a natural antibacterial agent to address the growing food safety challenges.

Construction of gastroretentive aminated chitosan coated (sunflower oil /alginate / i-carrageenan) floatable polymeric beads for prolonged release of Amoxicillin trihydrate

New gastroretentive floatable polymeric beads were developed for efficient encapsulation and prolonged release of amoxicillin trihydrate (AMT). Herein, sunflower oil (SFO) was entrapped into alginate (Alg)/iota carrageenan (i-CG) doubly networked polymeric beads, and followed by surface-coating with aminated chitosan (AmCs) layer. Diverse analysis tools were employed to investigate the chemical structure, thermal and morphological properties of the formulated [email protected] (SFO/Alg/i-CG) polymeric beads. The formulated polymeric beads exhibited exceptional floating ability exceeded 24 h without floating lag time. Additionally, approximately 93.29% of AMT-drug was successfully encapsulated into the floatable coated polymeric beads. The AMT-drug burst release at pH.1.2 was meaningfully dwindled with increasing AmCs concentration up to 4%., while a prolonged release manner took place up to 25 h. Kinetically, the release mechanism obeyed Peppas-Sahlin model, while the Fickian diffusion was the dominant. The in vitro bio-evaluation assessments revealed that coated polymeric beads possessed excellent mucoadhesion percent reached 93.333%, potent antimicrobial activity and respectable biodegradability under the physiological enzymatic conditions. The cytotoxicity assessment confirmed the safety of the formulated floatable polymeric beads with cell viability reached 96%, suggesting their potential applicability as effectual mucoadhesive carriers for the oral delivery of antibiotics.

Carrageenan/Chitin Nanowhiskers Cryogels for Vaginal Delivery of Metronidazole.

The development of polymeric carriers based on partially deacetylated chitin nanowhiskers (CNWs) and anionic sulfated polysaccharides is an attractive strategy for improved vaginal delivery with modified drug release profiles. This study focuses on the development of metronidazole (MET)-containing cryogels based on carrageenan (CRG) and CNWs. The desired cryogels were obtained by electrostatic interactions between the amino groups of CNWs and the sulfate groups of CRG and by the formation of additional hydrogen bonds, as well as by entanglement of carrageenan macrochains. It was shown that the introduction of 5% CNWs significantly increased the strength of the initial hydrogel and ensured the formation of a homogeneous cryogel structure, resulting in sustained MET release within 24 h. At the same time, when the CNW content was increased to 10%, the system collapsed with the formation of discrete cryogels, demonstrating MET release within 12 h. The mechanism of prolonged drug release was mediated by polymer swelling and chain relaxation in the polymer matrix and correlated well with the Korsmeyer-Peppas and Peppas-Sahlin models. In vitro tests showed that the developed cryogels had a prolonged (24 h) antiprotozoal effect against Trichomonas, including MET-resistant strains. Thus, the new cryogels with MET may be promising dosage forms for the treatment of vaginal infections.

Calcium phosphate incorporated in silk fibroin/methylcellulose based injectable hydrogel: Preparation, characterization, and in vitro biological evaluation for bone defect treatment.

Bone defect is still a challenging problem in orthopedic practice. Injectable bone substitutes that can fill different geometry of bone defect and improve biological environment for bone regeneration are attracting attention. Herein, silk fibroin (SF) is noticeable polymer regarding its biocompatible and biodegradable properties. Thus, the calcium phosphate particles incorporated in silk fibroin/methylcellulose (CAPs-SF/MC) and only methylcellulose (CAPs-MC) hydrogels are developed and compared their physicochemical properties. Both CAPs-hydrogels solutions can be administered with a low injectability force of ~6 N, and they require ~40-min to change to hydrogel at physiological temperature (37°C). The CAPs are evenly distributed throughout the hydrogel matrix and are capable transformed to bioactive hydroxyapatite at pH 7.4. The CAPs in CAPs-SF/MC have a smaller size than those in CAPs-MC. Moreover, CAPs-SF/MC exhibit gradual degradation, as prediction of the degradation mechanism by the Peppas-Sahlin model and show a greater ability to sustain CAPs release. CAPs-SF/MC has good biocompatibility with less cytotoxicity in a dose-dependent manner on mouse preosteoblast cell line (MC3T3-E1) when compared to CAPs-MC. CAPs-SF/MC hydrogels also have better possibility for promoting cell proliferation and differentiation. In conclusion SF incorporated into composite injectable hydrogel potentially improve biological characteristics and may provide clinical advantages.

Hot-melt extruded in situ gelling systems (MeltDrops Technology): Formulation development, in silico modelling and in vivo studies

In situ gelling systems (ISGS) can prolong retention time and bioavailability of ophthalmic solutions. The complexity and cost of ISGS avert their industrial scale-up and clinical implementation. In this study, we demonstrate novel application of hot-melt extrusion (HME) technology for continuous manufacturing of ISGS (MeltDrops Technology). Timolol maleate (TIM) and dorzolamide hydrochloride (DRZ) loaded MeltDrops were successfully developed using HME for glaucoma management, thereby resolving issues with batch manufacturing of ISGS, prolonging retention time thus improving bioavailability. The MeltDrops technology involves one-step, i.e., passing all the ingredients through an extruder at a screw speed between 20 and 50 rpm and barrel temperature of 80 °C. The comparative evaluation of MeltDrops and batch-processed ISGS demonstrated that MeltDrops exhibited better physical and chemical content uniformity. The extrusion temperature and screw speed were critical factors influencing content uniformity and properties of the MeltDrops. MeltDrops showed sustained drug release for > 12 h in vitro (TIM = 83.07%; DRZ = 60.43%, 12 h) versus marketed eyedrops. The developed MeltDrops followed Peppas-Sahlin model, combining Fickian diffusion and swelling processes. The in vivo study in New Zealand rabbits revealed superior effectiveness and safety of the MeltDrops as compared to the marketed eyedrops. Herein we conclude, MeltDrops would serve as a cutting-edge platform technology that can be used to manufacture various ISGS with one-step processability, cost-effectiveness, and improved product quality, which are otherwise processed by batch manufacturing that involves numerous complex processing steps.

Preparation, characterization and release kinetics of a multilayer encapsulated Perilla frutescens L. essential oil hydrogel bead

Encapsulation has been widely used as the protection of essential oils, which gives the possibility of their implementation as food preservatives. In this study, Perilla frutescens L. essential oil (PLEO) microcapsule powders were prepared firstly by spray drying method using octenyl succinic anhydride starch (OSAs) as wall material, and then they were further encapsulated by sodium alginate and chitosan via polyelectrolyte complex coacervates method. The best results were obtained by using 4 % of OSAs-PLEO microcapsule powders, 2 % of sodium alginate and 1.5 % of chitosan producing PLEO hydrogel beads with encapsulation efficiency of 61.29 % and loading degree of 41.11 %. Morphology observation showed PLEO hydrogel beads was a millimeter scale spherical particle. FTIR assay confirmed the physical embedding of OSAs on PLEO and the formation of complex coacervates between sodium alginate and chitosan. TG and DSC assay showed the chitosan/alginate/OSAs complex coacervates as wall materials substantially improved the thermal stability of PLEO. Besides, PLEO hydrogel beads had a better stability in aqueous and acidic food formulations, which achieved a complete and prolonged release of PLEO. The Peppas-Sahlin model was the best approach for PLEO release profile, and release phenomenon was mainly governed by Fickian diffusion.

Comparative Study of Cinnamon and Paprika Oleoresins Encapsulated by Spray Chilling and Particles from Gas Saturated Solutions Techniques: Evaluation of Physical Characteristics and Oleoresins Release in Food Simulated Media

In this study, cinnamon and paprika oleoresins were encapsulated by two technologies, respectively, spray chilling and particles from gas saturated solutions. Both technologies used palm oil as wall materials. The physical characteristics of the microparticles were compared as well as the oleoresins release behavior in high- and low-fat simulated food media. The spray chilling microparticles had an average diameter of 143.7 ± 1.5 µm, spherical shape, smooth surface, and passable flow property. In contrast, microparticles obtained by particles from gas saturated solutions (PGSS) showed an average diameter of 105.7 ± 0.6 µm, irregular shape, porous surface, poor flow property but higher encapsulation efficiency. In evaluating the compounds released in a simulated food medium, the spray chilling particles delivered 30.7%, while PGSS reached 23.1% after 1 h. Both microparticles well fitted the Kosmeyer-Peppas (R2 = 0.98 and 0.96 for spray chilling and PGSS) and Peppas-Sahlin models (R2 = 0.98 and 0.97 for spray chilling and PGSS). However, spray chilling microparticles showed a diffusion mechanism, while for PGSS ones erosion was the main mechanism. Despite the different physical characteristics, both microparticles proved to be possible facilitators in delivering oleoresins in food products.

β-Cyclodextrin inclusion complexes of combined Moroccan Rosmarinus officinalis, Lavandula angustifolia and Citrus aurantium volatile oil: production optimization and release kinetics in food models

ABSTRACT A combined volatile oil (VO) was extracted from Rosmarinus officinalis, Lavandula angustifolia and Citrus aurantium by simultaneous hydro- and steam-distillation, and encapsulated in β-cyclodextrin by co-precipitation. Response surface methodology (RSM) was used to optimize microencapsulation conditions. The variable recovered powder, VO retention degree, and inclusion efficiency were investigated based on two factors: solid-to-liquid and liquid-to-liquid (ethanol/water) ratios. The responses were influenced by the concentration of ethanol in the reaction mixture and the amount of VO used. VO release from the inclusion complexes was investigated in 10% ethanol and in 3% acetic acid. The obtained data were fitted to the first-order Korsmeyer-Peppas, Higuchi, and Peppas-Sahlin models. The Higuchi model gave the fittest approach for the VO release profile in both cases, showing that the release mechanism was controlled by Fickian diffusion.

Injectable hydrogels of enzyme-catalyzed cross-linked tyramine-modified gelatin for drug delivery

Enzymatically catalyzed cross-linking is a hydrogel fabrication method that generally is considered to have lower cytotoxicity than traditional chemical cross-linking methods. In order to optimize the properties of injectable hydrogels and expand their applications, an enzyme-catalyzed cross-linked injectable hydrogel was designed. The tyramine-modified gelatin (G-T) was formed into a stable injectable hydrogel by the combination of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) catalysis. 1H NMR spectroscopy was used to demonstrate the successful modification of gelatin by tyramine. The surface morphology of the prepared hydrogels was characterized jointly by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Rheological tests demonstrated the tunable mechanical strength, formation kinetics, shear thinning and good self-recovery properties of the hydrogels. In addition, the hydrogels can be formed into various shapes by injection. The hydrogel network structure is complex and interlaced, as such it is suitable to encapsulate drugs for controlled release. The drug release from the prepared hydrogels followed the Peppas–Sahlin model and belonged to Fickian diffusion. This study constructed injectable hydrogels through the enzyme-catalyzed cross-linking of modified gelatin and applied the hydrogels for drug release, which is expected to expand the application in biomedical fields.

Meropenem loaded 4-arm-polyethylene-succinimidyl-carboxymethyl ester and hyaluronic acid based bacterial resistant hydrogel

Developing an ideal vitreous substitute/implant is a current challenge. Moreover, implants (e.g., heart valves and vitreous substitutes), are associated with a high risk of bacterial infection when it comes in contact with cells at implant site. Due to infection, many implants fail, and the patient requires immediate surgery and suffers from post-operative problems. To overcome these problems in vitreous implants, we developed a bacterial resistant vitreous implant, where meropenem (Mer), an antibiotic, has been incorporated in a hydrogel prepared by crosslinking HA (deacetylated sodium hyaluronate) with 4-arm-polyethylene-succinimidyl-carboxymethyl-ester (PESCE). The HA-PESCE hydrogel may serve as a suitable artificial vitreous substitute (AVS). The pre-gel solutions of HA-PESCE without drug and with the drug are injectable through a 22 G needle, and the gel formation occurred in approx. 3 min: it indicates its suitability for in-situ gelation through vitrectomy surgery. The HA-PESCE hydrogel depicted desired biocompatibility, transparency (>90 %), water content (96 %) and sufficient viscoelasticity (G′ >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. The HA-Mer-PESCE hydrogel showed improved biocompatibility, suitable transparency (>90 %), high water content (96 %), and suitable viscoelasticity (G′ >100 Pa) calculated after 1 month in-vitro, which are suitable for vitreous substitute. Further, hydrogel strongly inhibits the growth of bacteria E.coli and S.aureus. The drug loaded hydrogel showed sustained in-vitro drug release by the Fickian diffusion-mediated process (by Korsmeyer-Peppas and Peppas Sahlin model). Thus, the developed hydrogel may be used as a potential bacterial resistant AVS.

Release kinetics of metronidazole from 3D printed silicone scaffolds for sustained application to the female reproductive tract

Sustained vaginal administration of antibiotics or probiotics has been proposed to improve treatment efficacy for bacterial vaginosis. 3D printing has shown promise for development of systems for local agent delivery. In contrast to oral ingestion, agent release kinetics can be fine-tuned by the 3D printing of specialized scaffold designs tailored for particular treatments while enhancing dosage effectiveness via localized sustained release. It has been challenging to establish scaffold properties as a function of fabrication parameters to obtain sustained release. In particular, the relationships between scaffold curing conditions, compressive strength, and drug release kinetics remain poorly understood. This study evaluates 3D printed scaffold formulation and feasibility to sustain the release of metronidazole, a commonly used antibiotic for BV. Cylindrical silicone scaffolds were printed and cured using three different conditions relevant to potential future incorporation of temperature-sensitive labile biologics. Compressive strength and drug release were monitored for 14d in simulated vaginal fluid to assess long-term effects of fabrication conditions on mechanical integrity and release kinetics. Scaffolds were mechanically evaluated to determine compressive and tensile strength, and elastic modulus. Release profiles were fitted to previous kinetic models to differentiate potential release mechanisms. The Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin models best described the release, indicating similarity to release from insoluble or polymeric matrices. This study shows the feasibility of 3D printed silicone scaffolds to provide sustained metronidazole release over 14d, with compressive strength and drug release kinetics tuned by the fabrication parameters.

Hybrid Hydrogels for Neomycin Delivery: Synergistic Effects of Natural/Synthetic Polymers and Proteins.

This paper reports new physical hydrogels obtained by the freezing/thawing method. They include pullulan (PULL) and poly(vinyl alcohol) (PVA) as polymers, bovine serum albumin (BSA) as protein, and a tripeptide, reduced glutathione (GSH). In addition, a sample containing PULL/PVA and lysozyme was obtained in similar conditions. SEM analysis evidenced the formation of networks with porous structure. The average pore size was found to be between 15.7 μm and 24.5 μm. All samples exhibited viscoelastic behavior typical to networks, the hydrogel strength being influenced by the protein content. Infrared spectroscopy analysis revealed the presence of intermolecular hydrogen bonds and hydrophobic interactions (more pronounced for BSA content between 30% and 70%). The swelling kinetics investigated in buffer solution (pH = 7.4) at 37 °C evidenced a quasi-Fickian diffusion for all samples. The hydrogels were loaded with neomycin trisulfate salt hydrate (taken as a model drug), and the optimum formulations (samples containing 10-30% BSA or 2% lysozyme) proved a sustained drug release over 480 min in simulated physiological conditions. The experimental data were analyzed using different kinetic models in order to investigate the drug release mechanism. Among them, the semi-empirical Korsmeyer-Peppas and Peppas-Sahlin models were suitable to describe in vitro drug release mechanism of neomycin sulfate from the investigated hybrid hydrogels. The structural, viscoelastic, and swelling properties of PULL/PVA/protein hybrid hydrogels are influenced by their composition and preparation conditions, and they represent important factors for in vitro drug release behavior.

Nanoparticles Obtained from Zein for Encapsulation of Mesalazine.

We encapsulated MSZ in zein nanoparticles (NP-ZN) using a desolvation method followed by drying in a mini spray dryer. These nanoparticles exhibited a size of 266.6 ± 52 nm, IPD of 0.14 ± 1.1 and zeta potential of -36.4 ± 1.5 mV, suggesting colloidal stability. Quantification using HPLC showed a drug-loaded of 43.8 µg/mg. SEM demonstrated a spherical morphology with a size variation from 220 to 400 nm. A FTIR analysis did not show drug spectra in the NPs in relation to the physical mixture, which suggests drug encapsulation without changing its chemical structure. A TGA analysis showed thermal stability up to 300 °C. In vitro release studies demonstrated gastroresistance and a sustained drug release at pH 7.4 (97.67 ± 0.32%) in 120 h. The kinetic model used for the release of MSZ from the NP-ZN in a pH 1.2 medium was the Fickian diffusion, in a pH 6.8 medium it was the Peppas-Sahlin model with the polymeric relaxation mechanism and in a pH 7.4 medium it was the Korsmeyer-Peppas model with the Fickian release mechanism, or "Case I". An in vitro cytotoxicity study in the CT26.WT cell line showed no basal cytotoxicity up to 500 μg/mL. The NP-ZN showed to be a promising vector for the sustained release of MSZ in the colon by oral route.

Orally administered docetaxel-loaded chitosan-decorated cationic PLGA nanoparticles for intestinal tumors: formulation, comprehensive in vitro characterization, and release kinetics.

Intestinal cancers are the third most lethal cancers globally, beginning as polyps in the intestine and spreading with a severe metastatic tendency. Chemotherapeutic drugs used in the treatment of intestinal tumors are usually formulated for parenteral administration due to poor solubility and bioavailability problems. Pharmaceutically, clinical failure due to a drug's wide biodistribution and non-selective toxicity is one of the major challenges of chemotherapy. In addition, parenteral drug administration in chronic diseases that require long-term drug use, such as intestinal tumors, is challenging in terms of patient compliance and poses a burden in terms of health economy. Especially in the field of chemotherapy research, oral chemotherapy is a subject that has been intensively researched in recent years, and developments in this field will provide serious breakthroughs both scientifically and socially. Development of orally applicable nanodrug formulations that can act against diseases seen in the distant region of the gastrointestinal tract (GIT), such as intestinal tumor, brings with it a series of difficulties depending on the drug and/or GIT physiology. The aim of this study is to develop an oral nanoparticle drug delivery system loaded with docetaxel (DCX) as an anticancer drug, using poly(lactic-co-glycolic acid) (PLGA) as nanoparticle material, and modified with chitosan (CS) to gain mucoadhesive properties. In this context, an innovative nanoparticle formulation that can protect orally administered DCX from GIT conditions and deliver the drug to the intestinal tumoral region by accumulating in mucus has been designed. For this purpose, DCX-PLGA nanoparticles (NPs) and CS/DCX-PLGA NPs were prepared, and their in vitro characteristics were elucidated. Nanoparticles around 250-300 nm were obtained. DCX-PLGA NPs had positive surface charge with CS coating. The formulations have the potential to deliver the encapsulated drug to the bowel according to the in vitro release studies in three different simulated GIT fluids for approximately 72 h. Mucin interaction and penetration into the artificial mucus layer were also investigated in detail, and the mucoadhesive and mucus-penetration characteristics of the formulations were examined. Furthermore, in vitro release kinetic studies of the NPs were elucidated. DCX-PLGA NPs were found to be compatible with the Weibull model, and CS/DCX-PLGA NPs were found to be compatible with the Peppas-Sahlin model. Within the scope of in vitro cytotoxicity studies, the drug-loaded NPs showed significantly higher cytotoxicity than a DCX solution on the HT-29 colon cell line, and CS/DCX-PLGA showed the highest cytotoxicity (p < 0.05). According to the permeability studies on the Caco-2 cell line, the CS/DCX-PLGA formulation increased permeability by 383% compared to free DCX (p < 0.05). In the light of all results, CS/DCX-PLGA NPs can offer a promising and innovative approach as an oral anticancer drug-loaded nanoformulation for intestinal tumors.

The Formation of Self-Assembled Nanoparticles Loaded with Doxorubicin and d-Limonene for Cancer Therapy.

Self-assembled nanoparticles present unique properties that have potential applications in the development of a successful drug delivery system. Doxorubicin (DOX) is an important anti-neoplastic anthracycline chemotherapeutic drug widely described. However, it suffers from serious dose-dependent cardiotoxicity. d-Limonene is a major constituent of numerous citrus oils that is considered a specific monoterpene against free radicals producing antioxidant activity. Herein, we aimed to design three types of self-assembled nanodelivery systems (nanoemulsion, niosomes, and polylactide nanoparticles) for loading both DOX and d-limonene to enhance the solubilization of d-limonene and provide antioxidant activity with excellent anticancer activity. As confirmed by dynamic light scattering and transmission electron microscopy, the nanoparticles were prepared successfully with diameter sizes of 52, 180, and 257 nm for the DOX-loaded nanoemulsion, niosomes, and polylactide nanoparticles, respectively. The zeta potential values were above -30 mV in all cases, which confirms the formation of stable nanoparticles. The loading efficiency of DOX was the highest in the case of the DOX-loaded nanoemulsion (75.8%), followed by niosomes (62.8%), and the least was in the case of polylactide nanoparticles with a percentage of 50.2%. The in vitro release study of the DOX-loaded nanoparticles showed a sustained release profile of doxorubicin with the highest release in the case of DOX-loaded PDLLA nanoparticles. The kinetic release model for all developed nanoparticles was the Peppas-Sahlin model, demonstrating DOX release through Fickian diffusion phenomena. Moreover, all developed nanoparticles maintain the antioxidant activity of d-limonene. The cytotoxicity study of the DOX-loaded nanoparticles showed concentration-dependent anticancer activity with excellent anticancer activity in the case of the DOX-loaded nanoemulsion and polylactide nanoparticles. These nanoparticles will be further studied in vivo to prove the cardioprotective effect of d-limonene in combination with DOX.