Highly Compressible, Superabsorbent, and Biocompatible Hybrid Cryogel Constructs Comprising Functionalized Chitosan and St. John's Wort Extract.

Biobased porous hydrogels enriched with phytocompounds-rich herbal extracts have aroused great interest in recent years, especially in healthcare. In this study, new macroporous hybrid cryogel constructs comprising thiourea-containing chitosan (CSTU) derivative and a Hypericum perforatum L. extract (HYPE), commonly known as St John's wort, were prepared by a facile one-pot ice-templating strategy. Benefiting from the strong interactions between the functional groups of the CSTU matrix and those of polyphenols in HYPE, the hybrid cryogels possess excellent liquid absorption capacity, mechanical resilience, antioxidant performance, and a broad spectrum of antibacterial activity simultaneously. Thus, owing to their design, the hybrid constructs exhibit an interconnected porous architecture with the ability to absorb over 33 and 136 times their dry weight, respectively, when contacted with a phosphate buffer solution (pH 7.4) and an acidic aqueous solution (pH 2). These cryogel constructs have extremely high compressive strengths ranging from 839 to 1045 kPa and withstand elevated strains of over 70% without developing fractures. Moreover, the water-swollen hybrid cryogels with the highest HYPE content revealed a complete and instant shape recovery after uniaxial compression. The incorporation of HYPE into CSTU cryogels enabled substantial improvement in scavenging reactive oxygen species and an expanded antibacterial spectrum toward multiple pathogens, including Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Candida albicans). Cell viability experiments demonstrated the cytocompatibility of the 3D cryogel constructs, which did not induce changes in the fibroblast morphology. This work showcases a simple and effective strategy to immobilize HYPE extracts on CSTU 3D networks, allowing the development of novel multifunctional platforms with promising potential in hemostasis, wound dressing, and dermal regeneration scaffolds.

Xanthan-Based Materials as a Platform for Heparin Delivery.

Heparin (Hep), with its anticoagulant activity, antiangiogenic and apoptotic effects, and growth factor binding, plays an important role in various biological processes. Formulations as drug delivery systems protect its biological activity, and limit the potential side effects of faulty administration. The objective of this study was to develop novel xanthan-based materials as a delivery carrier for heparin. The materials exhibited remarkable elastic behavior and toughness without any crack development within the network, which also support their application for tissue engineering. It was found that all materials possessed the ability to control the release of heparin, according to the Korsmeyer-Peppas release model. All Hep-containing materials caused significant exchanges of the activated partial thromboplastin time (aPTT) and prothrombin time (PT) parameters, indicating that formulated natural/natural synthetic polymeric networks conserved heparin's biological activity and its ability to interrupt the blood coagulation cascade. The obtained results confirmed that developed materials could be carriers for the controlled release of heparin, with potential applications in topical administration.

Advanced 3D Magnetic Scaffolds for Tumor-Related Bone Defects.

The need for bone substitutes is a major challenge as the incidence of serious bone disorders is massively increasing, mainly attributed to modern world problems, such as obesity, aging of the global population, and cancer incidence. Bone cancer represents one of the most significant causes of bone defects, with reserved prognosis regarding the effectiveness of treatments and survival rate. Modern therapies, such as hyperthermia, immunotherapy, targeted therapy, and magnetic therapy, seem to bring hope for cancer treatment in general, and bone cancer in particular. Mimicking the composition of bone to create advanced scaffolds, such as bone substitutes, proved to be insufficient for successful bone regeneration, and a special attention should be given to control the changes in the bone tissue micro-environment. The magnetic manipulation by an external field can be a promising technique to control this micro-environment, and to sustain the proliferation and differentiation of osteoblasts, promoting the expression of some growth factors, and, finally, accelerating new bone formation. By incorporating stimuli responsive nanocarriers in the scaffold's architecture, such as magnetic nanoparticles functionalized with bioactive molecules, their behavior can be rigorously controlled under external magnetic driving, and stimulates the bone tissue formation.

Drug-Loaded Polymeric Particulated Systems for Ophthalmic Drugs Release.

Drug delivery to the anterior or posterior segments of the eye is a major challenge due to the protection barriers and removal mechanisms associated with the unique anatomical and physiological nature of the ocular system. The paper presents the preparation and characterization of drug-loaded polymeric particulated systems based on pre-emulsion coated with biodegradable polymers. Low molecular weight biopolymers (chitosan, sodium hyaluronate and heparin sodium) were selected due to their ability to attach polymer chains to the surface of the growing system. The particulated systems with dimensions of 190-270 nm and a zeta potential varying from -37 mV to +24 mV depending on the biopolymer charges have been obtained. Current studies show that particles release drugs (dexamethasone/pilocarpine/bevacizumab) in a safe and effective manner, maintaining therapeutic concentration for a longer period of time. An extensive modeling study was performed in order to evaluate the drug release profile from the prepared systems. In a multifractal paradigm of motion, nonlinear behaviors of a drug delivery system are analyzed in the fractal theory of motion, in order to correlate the drug structure with polymer. Then, the functionality of a SL(2R) type "hidden symmetry" implies, through a Riccati type gauge, different "synchronization modes" (period doubling, damped oscillations, quasi-periodicity and intermittency) during the drug release process. Among these, a special mode of Kink type, better reflects the empirical data. The fractal study indicated more complex interactions between the angiogenesis inhibitor Bevacizumab and polymeric structure.

Paclitaxel-Loaded Magnetic Nanoparticles Based on Biotinylated N-Palmitoyl Chitosan: Synthesis, Characterization and Preliminary In Vitro Studies.

A considerable interest in cancer research is represented by the development of magnetic nanoparticles based on biofunctionalized polymers for controlled-release systems of hydrophobic chemotherapeutic drugs targeted only to the tumor sites, without affecting normal cells. The objective of the paper is to present the synthesis and in vitro evaluation of the nanocomposites that include a magnetic core able to direct the systems to the target, a polymeric surface shell that provides stabilization and multi-functionality, a chemotherapeutic agent, Paclitaxel (PTX), and a biotin tumor recognition layer. To our best knowledge, there are no studies concerning development of magnetic nanoparticles obtained by partial oxidation, based on biotinylated N-palmitoyl chitosan loaded with PTX. The structure, external morphology, size distribution, colloidal and magnetic properties analyses confirmed the formation of well-defined crystalline magnetite conjugates, with broad distribution, relatively high saturation magnetization and irregular shape. Even if the ability of the nanoparticles to release the drug in 72 h was demonstrated, further complex in vitro and in vivo studies will be performed in order to validate the magnetic nanoparticles as PTX delivery system.

In Vitro Antioxidant, Antitumor and Photocatalytic Activities of Silver Nanoparticles Synthesized Using Equisetum Species: A Green Approach.

The ethanolic extracts of three Equisetum species (E. pratense Ehrh., E. sylvaticum L. and E. telmateia Ehrh.) were used to reduce silver ions to silver nanoparticles (AgNPs). The synthesized AgNPs were characterized using UV-Vis spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), Energy Dispersive X-ray (EDX), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) measurements. FTIR data revealed the functional groups of biomolecules involved in AgNPs synthesis, such as O-H, C-H, C=O, C-O, and C-C. EDX spectroscopy was used to highlight the presence of silver, while DLS spectroscopy provided information on the mean diameter of AgNPs, that ranged from 74.4 to 314 nm. The negative Zeta potential values (-23.76 for Ep-AgNPs, -29.54 for Es-AgNPs and -20.72 for Et-AgNPs) indicate the stability of the obtained colloidal solution. The study also focused on establishing the photocatalytic activity of AgNPs, which is an important aspect in terms of removing organic dyes from the environment. The best photocatalytic activity was observed for AgNPs obtained from E. telmateia, which degraded malachite green in a proportion of 97.9%. The antioxidant action of the three AgNPs samples was highlighted comparatively through four tests, with the best overall antioxidant capacity being observed for AgNPs obtained using E. sylvaticum. Moreover, the biosynthesized AgNPs showed promising cytotoxic efficacy against cancerous cell line MG63, the AgNPs obtained from E. sylvaticum L. providing the best result, with a LD50 value around 1.5 mg/mL.

Magnetic Composite Scaffolds for Potential Applications in Radiochemotherapy of Malignant Bone Tumors.

Background and objectives: Cancer is the second leading cause of death globally, an alarming but expected increase. In comparison to other types of cancer, malignant bone tumors are unusual and their treatment is a real challenge. This paper's main purpose is the study of the potential application of composite scaffolds based on biopolymers and calcium phosphates with the inclusion of magnetic nanoparticles in combination therapy for malignant bone tumors. Materials and Methods: The first step was to investigate if X-rays could modify the scaffolds' properties. In vitro degradation of the scaffolds exposed to X-rays was analyzed, as well as their interaction with phosphate buffer solutions and cells. The second step was to load an anti-tumoral drug (doxorubicin) and to study in vitro drug release and its interaction with cells. The chemical structure of the scaffolds and their morphology were studied. Results: Analyses showed that X-ray irradiation did not influence the scaffolds' features. Doxorubicin release was gradual and its interaction with cells showed cytotoxic effects on cells after 72 h of direct contact. Conclusions: The obtained scaffolds could be considered in further studies regarding combination therapy for malignant bone tumors.

Scaffolds Based on Collagen, Hyaluronan and Sericin with Potential Applications as Controlled Drug Delivery System.

Natural proteins have been extensively studied as matrices for tissue engineering, due to their excellent biocompatibility and biological properties associated with increasing cell proliferation. By generating complex materials, cell and tissue functions can be tailored to obtain a specific direction, according to the medical needs. The aim of this paper was to obtain scaffolds based on collagen, hyaluronan and sericin, with morphology and physical-chemical properties adequate for controlled drug delivery systems. In this aim various tests were performed: in vitro swelling and degradation studies, Fourier Transform Infrared spectroscopy (FT-IR), Scanning Electronic Microscopy (SEM) and thermogravimetric analysis. Loading and releasing of ibuprofen is also discussed. The results indicate that scaffolds based on collagen, hyaluronan and sericin have a porous structure, strength and stability adequate for skin tissue engineering. The obtained scaffolds swell, degrade and have controlled drug release properties in simulated biological fluids.

Bacterial nanocellulose loaded with bromelain and nisin as a promising bioactive material for wound debridement.

The bacterial nanocellulose (BnC) membranes were produced extracellularly by a novel aerobic acetic acid bacterium Komagataeibacter melomenusus. The BnC was modified in situ by adding carboxymethyl cellulose (CMC) into the culture media, obtaining a BnC-CMC product with denser fibril arrangement, improved rehydration ratio and elasticity in comparison to BnC. The proteolytic enzyme bromelain (Br) and antimicrobial peptide nisin (N) were immobilized to BnC matrix by ex situ covalent binding and/or adsorption. The optimal Br immobilization conditions towards the maximized specific proteolytic activity were investigated by response surface methodology as factor variables. At optimal conditions, i.e., 8.8 mg/mL CMC and 10 mg/mL Br, hyperactivation of the enzyme was achieved, leading to the specific proteolytic activity of 2.3 U/mg and immobilization efficiency of 39.1 %. The antimicrobial activity was observed against Gram-positive bacteria (S. epidermidis, S. aureus and E. faecalis) for membranes with immobilized N and was superior when in situ modified BnC membranes were used. N immobilized on the BnC or BnC-CMC membranes was cytocompatible and did not cause changes in normal human dermal fibroblast cell morphology. BnC membranes perform as an efficient carrier for Br or N immobilization, holding promise in wound debridement and providing antimicrobial action against Gram-positive bacteria, respectively.

In Vitro Biological Evaluation of an Alginate-Based Hydrogel Loaded with Rifampicin for Wound Care.

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze-thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of hydrogen-bond-based interactions between alginate and Rifampicin were identified. A concentration of 0.69% Rifampicin was found in the polymeric matrix using HPLC analysis and spectrophotometric UV-Vis methods. The hydrogel's morphology was evaluated by scanning electron microscopy, and various sizes and shapes of pores, ranging from almost spherical geometries to irregular ones, with a smooth surface of the pore walls and high interconnectivity in the presence of the drug, were identified. The hydrogels are bioadhesive, and the adhesion strength increased after Rifampicin was encapsulated into the polymeric matrix, which suggests that these compositions are suitable for wound dressings. Antimicrobial activity against S. aureus and MRSA, with an increased effect in the presence of the drug, was also found in the newly prepared hydrogels. In vitro biological evaluation demonstrated the cytocompatibility of the hydrogels and their ability to stimulate cell multiplication and mutual cell communication. The in vitro scratch assay demonstrated the drug-loaded alginate-grafted poly(N-vinylcaprolactam) hydrogel's ability to stimulate cell migration and wound closure. All of these results suggest that the prepared hydrogels can be used as antimicrobial materials for wound healing and care applications.

Hydrogels with Antioxidant Microparticles Systems Based on Hyaluronic Acid for Regenerative Wound Healing.

This research focuses on the synthesis of hydrogels exhibiting enhanced antioxidant properties derived from hyaluronic acid (HA) and poly(ethylene brassylate-co-squaric acid) (PEBSA), a copolymacrolactone that have the ability to be used in drug delivery applications. Quercetin (Q), a bioflavonoid with strong antioxidant properties, is employed as a bioactive compound. The biomolecule is encapsulated in the polymeric network using different entrapment techniques, including the initial formation of a complex between PEBSA and Q, which is demonstrated through the dynamic light scattering technique. Fourier transform infrared spectroscopy (FT-IR) and rheological studies confirm the formation of the hydrogels, revealing the occurrence of physical interactions between the synthetic polymer and the polysaccharide. Moreover, the hydrogels demonstrate biocompatible properties after direct contact with the HDFa cell line and antioxidant properties, as revealed by DPPH tests.

Evaluation of hyaluronic acid-polymacrolactone hydrogels with 3D printing capacity.

The implementation of personalized patches, tailored to individual genetic profiles and containing specific amounts of bioactive substances, has the potential to produce a transformative impact within the medical sector. There are several methods of designing scaffolds in the context of personalized medicine, with three-dimensional (3D) printing emerging as a pivotal technique. This innovative approach can be used to construct a wide variety of pharmaceutical dosage forms, characterized by variations in shape, release profile, and drug combinations, allowing precise dose individualization and the incorporation of multiple therapeutic agents. To expand the potential and applicability of personalized medicine, particularly with regards to indomethacin (IND), a drug necessitating individualized dosing, this study proposes the development of new transdermal delivery systems for IND based on hyaluronic acid and a polylactone synthesized within our research group, namely poly(ethylene brasilate-co-squaric acid) (PEBSA). The obtained systems were characterized in terms of their swelling capacity, rheological behavior, and morphological characteristics that highlighted the formation of stable three-dimensional networks. To impart specific shape and geometry to the structures, multi-component systems based on PEBSA, HA, and methacrylate gelatin were obtained. The scaffolds were loaded with IND and subsequently 3D printed. The release capacity of IND and its dependence on the relative ratios of the components comprising the scaffold composition were highlighted. The cytocompatibility studies revealed the successful development of biocompatible and noncytotoxic systems.

In Vitro and In Vivo Analysis of the Mg-Ca-Zn Biodegradable Alloys.

The objective of this work was to analyze the in vitro and in vivo tests of a novel Mg-based biodegradable alloy-Mg-0.5%Ca-with various amounts of Zn (0.5, 1, 1.5, 2.0, and 3.0 wt.%). In terms of in vitro biocompatibility, MTT and Calcein-AM cell viability assays, performed on the MG-63 cell line through the extract method, revealed that all five alloy extracts are non-cytotoxic at an extraction ratio of 0.025 g alloy per mL of cell culture medium. In the in vivo histological analysis, Mg-0.5Ca-1.5Zn demonstrated exceptional potential for stimulating bone remodeling and showed excellent biocompatibility. It was observed that Mg-0.5Ca-0.5Zn, Mg-0.5Ca-1.5Zn, and Mg-0.5Ca-3Zn displayed good biocompatibility. Furthermore, the histological examination highlighted the differentiation of periosteal cells into chondrocytes and subsequent bone tissue replacement through endochondral ossification. This process highlighted the importance of the initial implant's integrity and the role of the periosteum. In summary, Mg-0.5Ca-1.5Zn stands out as a promising candidate for bone regeneration and osseointegration, supported by both in vitro and in vivo findings.

Can Combining Hyaluronic Acid and Physiotherapy in Knee Osteoarthritis Improve the Physicochemical Properties of Synovial Fluid?

Known as the degenerative disease of the knee with the highest prevalence, knee osteoarthritis (KOA) is characterized by a gradual destructive mechanism that, in severe cases, can provoke the need for total knee substitution. As the disease progresses, various enzymatic, immunological, and inflammatory processes abnormally degrade hyaluronic acid (HA), SF's main component, and affect the concentrations of specific proteins, with the final results seriously endangering synovial fluid (SF)'s rheological and tribological features and characteristics. No effective treatments have been found to stop the progression of KOA, but the injection of HA-based viscoelastic gels has been considered (alone or combined with physiotherapy (PT)) as an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the characteristics of SF, SF aspirated from groups treated for KOA (HA Kombihylan® and groups that received Kombihylan® and complex PT) was analyzed and compared from analytical, spectrophotometrical, and rheological perspectives. In the patients treated with PT, the SF extracted 6 weeks after viscosupplementation had a superior elastic modulus (G') and viscous moduli (G″), as well as a homogeneous distribution of proteins and polysaccharides. The viscosupplementation fluid improved the bioadhesive properties of the SF, and the use of the viscosupplementation fluid in conjunction with PT was found to be favorable for the distribution of macromolecules and phospholipids, contributing to the lubrication process and the treatment of OA-affected joints.

New Methacrylated Biopolymer-Based Hydrogels as Localized Drug Delivery Systems in Skin Cancer Therapy.

The aim of the present work was to obtain drug-loaded hydrogels based on combinations of dextran, chitosan/gelatin/xanthan, and poly (acrylamide) as a sustained and controlled release vehicle of Doxorubicin, a drug used in skin cancer therapy that is associated with severe side effects. Hydrogels for use as 3D hydrophilic networks with good manipulation characteristics were produced using methacrylated biopolymer derivatives and the methacrylate group's polymerization with synthetic monomers in the presence of a photo-initiator, under UV light stimulation (365 nm). Transformed infrared spectroscopy analysis (FT-IR) confirmed the hydrogels' network structure (natural-synthetic composition and photocrosslinking), while scanning electron microscopy (SEM) analysis confirmed the microporous morphology. The hydrogels are swellable in simulated biological fluids and the material's morphology regulates the swelling properties: the maximum swelling degree was obtained for dextran-chitosan-based hydrogels because of their higher porosity and pore distribution. The hydrogels are bioadhesive on a biological simulating membrane, and values for the force of detachment and work of adhesion are recommended for applications on skin tissue. The Doxorubicin was loaded into the hydrogels and the drug was released by diffusion for all the resulting hydrogels, with small contributions from the hydrogel networks' relaxation. Doxorubicin-loaded hydrogels are efficient on keratinocytes tumor cells, the sustained released drug interrupting the cells' division and inducing cell apoptosis; we recommend the obtained materials for the topical treatment of cutaneous squamous cell carcinoma.

Polysaccharides-Calcium Phosphates Composite Beads as Bone Substitutes for Fractures Repair and Regeneration.

The tendency of population aging is continuously increasing, which is directly correlated with a significative number of associated pathologies. Several metabolic bone diseases such as osteoporosis or chronic kidney disease-mineral and bone disorders involve a high risk of fractures. Due to the specific fragility, bones will not self-heal and supportive treatments are necessary. Implantable bone substitutes, a component of bone tissue engineering (BTE) strategy, proved to be an efficient solution for this issue. The aim of this study was to develop composites beads (CBs) with application in the complex field of BTE, by assembling the features of both biomaterials' classes: biopolymers (more specific, polysaccharides: alginate and two different concentrations of guar gum/carboxymethyl guar gum) and ceramics (more specific, calcium phosphates), in a combination described for the first time in the literature. The CBs prepared by double crosslinking (ionic and physically) showed adequate physico-chemical characteristics and capabilities (morphology, chemical structure and composition, mechanical strength, and in vitro behaviour in four different acellular simulated body fluids) for bone tissue repair. Moreover, preliminary in vitro studies on cell cultures highlighted that the CBs were free of cytotoxicity and did not affect the morphology and density of cells. The results indicated that the beads based on a higher concentration of guar gum have superior properties than those with carboxymetilated guar, especially in terms of mechanical properties and behaviour in simulated body fluids.

Effect of Filler Types on Cellulose-Acetate-Based Composite Used as Coatings for Biodegradable Magnesium Implants for Trauma.

Magnesium alloys are considered one of the most promising materials for biodegradable trauma implants because they promote bone healing and exhibit adequate mechanical strength during their biodegradation in relation to the bone healing process. Surface modification of biodegradable magnesium alloys is an important research field that is analyzed in many publications as the biodegradation due to the corrosion process and the interface with human tissue is improved. The aim of the current preliminary study is to develop a polymeric-based composite coating on biodegradable magnesium alloys by the solvent evaporation method to reduce the biodegradation rate much more than in the case of simple polymeric coatings by involving some bioactive filler in the form of particles consisting of hydroxyapatite and magnesium. Various techniques such as SEM coupled with EDS, FTIR, and RAMAN spectroscopy, and contact angle were used for the structural and morphological characterization of the coatings. In addition, thermogravimetric analysis (TGA) was used to study the effect of filler particles on polymer thermostability. In vitro cytotoxicity assays were performed on MG-63 cells (human osteosarcomas). The experimental analysis highlights the positive effect of magnesium and hydroxyapatite particles as filler for cellulose acetate when they are used alone from biocompatibility and surface analysis points of view, and it is not recommended to use both types of particles (hydroxyapatite and magnesium) as hybrid filling. In future studies focused on implantation testing, we will use only CA-based composite coatings with one filler on magnesium alloys because these composite coatings have shown better results from the in vitro testing point of view for future potential orthopedic biodegradable implants for trauma.

Assessing the Antioxidant Properties, In Vitro Cytotoxicity and Antitumoral Effects of Polyphenol-Rich Perilla leaves Extracts.

(1) Background: This study aimed to outline the antioxidant, antitumoral, and cytotoxic proprieties of various types of Perilla frutescens extracts obtained from the leaves of the species. (2) Methods: We determined total polyphenols, flavonoids and anthocyanins contents, as well as the in vitro antioxidant, antitumoral, and cytotoxic actions in three types of ethanolic extracts (E1, E2, E3) and in three types of acetone: ethanol extracts (A1, A2, A3) of Perilla frutescens according to standardized procedures. (3) Results: We found that Perilla frutescens ethanolic extracts had the highest total phenol and anthocyanins concentrations. The flavonoids concentration was not statistically different between the extracts. The iron chelating capacity, hydroxyl radical scavenging capacity, superoxide anion radical scavenging capacity, and lipoxygenase inhibition capacity showed a significant increase with higher concentrations of Perilla frutescens extracts, particularly the ethanolic extracts. Perillyl alcohol had greater cytotoxic capacity in the MG-63 cell line and E1 extract showed similar significant cytotoxic effects in the A431 cell line. (4) Conclusions: Both ethanolic and acetone-ethanol extracts from Perilla frutescens exhibited important antioxidant and antitumoral actions in vitro, which proportionally increased with concentration. The cytotoxic threshold determined in this study for various types of extracts could help determine the best dosage with the maximum antioxidant and antitumoral potential. Our results could serve as a basis for further studies that will investigate the cytotoxic effects of Perilla frutescens variants on various types of cancer cell lines.

Development of Vaginal Carriers Based on Chitosan-Grafted-PNIPAAm for Progesterone Administration.

Chitosan-based hydrogels possess numerous advantages, such as biocompatibility and non-toxicity, and it is considered a proper material to be used in biomedical and pharmaceutical applications. Vaginal administration of progesterone represents a viable alternative for maintaining pregnancy and reducing the risk of miscarriage and in supporting the corpus luteum during fertilization cycles. This study aimed to develop new formulations for vaginal administration of progesterone (PGT). A previously synthesized responsive chitosan-grafted-poly (N-isopropylacrylamide) (CS-g-PNIPAAm) was formulated in various compositions with polyvinyl alcohol (PVA) as external crosslinking agent to obtain pH- and temperature-dependent hydrogels; the hydrogels had the capacity to withstand shear forces encountered in the vagina due to its mechanism of swelling once in contact with vaginal fluids. Three different hydrogels based on grafted chitosan were analyzed via Fourier-transform infrared spectroscopy (FTIR), swelling tests, in vitro drug release, and bioadhesion properties by TA.XTplus texture analysis. A higher amount of PVA decreased the swelling and the bioadhesion capacities of the hydrogel. All hydrogels showed sensitivity to temperature and pH in terms of swelling and in vitro delivery characteristics. By loading progesterone, the studied hydrogels seemed to possess even higher sensitivity than drug-free matrices. The release profile of the active substance and the bioadhesion characteristics recommended the CS-g-PNIPAAm/PVA 80/20 +PGT (P1) hydrogel as a proper constituent for the vaginal formulation for progesterone administration.

Antihyperglycemic effect of Vernonia amygdalina and in vitro evaluation of its antiproliferative activity on human osteosarcoma MG-63.

Introduction: the leaves of Vernonia amygdalina (V. amygdalina) are consumed as food in sub-Saharan Africa (SSA). In traditional medicine, this plant is widely used in the treatment of cancer and diabetes mellitus. In the present study, we evaluated the antihyperglycemic and the antiproliferative activities of the hydroalcoholic extract of V. amygdalina leaves (HAEVa). Methods: we conducted an experimental descriptive and analytical study with a prospective data collection from May 2019 to July 2020. For the in vivo study, the experiments were carried out on albino male rats of Wistar strain (Rattus norvegicus). Antihyperglycemic activity was performed in vivo in dexamethasone-induced insulin-resistant rats using the oral glucose tolerance test (OGTT). The biocompatibility and the antiproliferative activity of extract were performed in vitro respectively on rabbit primary dermal fibroblasts (RPDF) and human osteosarcoma MG-63 cells using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The data were analyzed with the GraphPad Prism software version 5.0.3. The statistical analyses were obtained by the analysis of variance (ANOVA), followed by Bonferroni´s post-test. P<0.05 was considered as the minimal level of statistical significance. Results: regarding to the antiproliferative investigation, extract at 125, 250 µg/mL exhibited a significant cytotoxic effect on human osteosarcoma MG-63 compared to the vehicle (p<0.001) in a dose-response manner after 24h, 48h of exposure to HAEVa. Interestingly, HAEVa in concentrations of 125 and 250µg/ml showed no cytotoxicity (p>0.05) on RPDF after the different times of exposure. However, HAEVa in a high concentration of 500 µg/mL wasn´t biocompatible with RPDF. HAEVa also prevented postprandial blood glucose level in dexamethasone-induced insulin-resistant rats at both doses tested (p>0.05 and p<0.01 at doses of 50 and 100 mg/kg respectively). Conclusion: the results of this study suggest that HAEVa has antiproliferative properties on MG-63 osteosarcoma in vitro and also inhibits in vivo the postprandial blood glucose level in dexamethasone-induced insulin-resistant rats.