Candida auris Infection, a Rapidly Emerging Threat in the Neonatal Intensive Care Units: A Systematic Review.

(1) Background: In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. Candida auris, in particular, has become a significant global concern, causing infections in both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is a limited understanding of the clinical course and transmission dynamics of neonatal systemic Candida auris infections, hindering effective prevention and management. This study focused on the epidemiologic data, the clinical presentation, risk factors, and outcome of C. auris infection in neonatal population. (2) Methods: A systematic review of the literature using PubMed and Scopus databases until December 2023 was conducted. (3) Results: A total of 24 relevant studies were identified, encompassing 476 documented cases of Candida auris infection in neonates. Prematurity emerged as a primary risk factor, alongside total parenteral nutrition, central line insertion, mechanical ventilation, and prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported in 12% of cases. Treatment strategies varied, with amphotericin B predominantly used as monotherapy, while combination antifungal agents were used in 44% of cases. Notably, 97.4% of cases exhibited fluconazole resistance, and 67.1% showed resistance to amphotericin B. Limited data were available on resistance to other antifungal agents. (4) Conclusions: Despite the rarity of neonatal Candida auris infections, their global occurrence necessitates comprehensive preparedness in patient care. A deeper understanding of Candida auris pathogenesis is crucial for developing effective strategies to control and prevent neonatal infections caused by this pathogen.

A well child with prolonged oral thrush: an unexpected diagnostic journey.

Oral thrush is a familiar presentation in both general practice and paediatrics, and is usually responsive to treatment in the community. Here, we present the diagnostic journey of a previously well boy aged 3 years who presented with treatment-resistant thrush and describe how 'unexpected' results led to eventual diagnosis and management. This intriguing case was managed jointly by district hospital general paediatric team and tertiary hospital specialist teams.

Extrauterine Growth Restriction and Optimal Growth of Very Preterm Neonates: State of the Art.

Over the last few decades, there has been an ongoing debate over both the optimal feeding mode for very premature neonates (VPN) as well as what their optimal growth should be. Despite the American Academy of Pediatric declaring since 1997 that the growth of VPN should follow the trajectory of intrauterine fetal growth, differences of opinion persist, feeding policies keep changing, and the growth and development of VPN remains extremely variable not only between countries, but even between neighboring neonatal units. Even the appropriate terminology to express poor postnatal growth (extrauterine growth restriction (EGR) and postnatal growth failure (PGF)) remains a subject of ongoing discussion. A number of recent publications have shown that by implementing breast milk fortification and closely following growth and adjusting nutrition accordingly, as per the consensus guidelines of the major Neonatal Societies, we could achieve growth that closely follows birth centiles. A recent position paper from EPSGAN recommending targeted nutritional support to cover the energy and protein deficits sustained by VPN during periods of critical illness further strengthens the above findings. Conclusion: We can promote better growth of VPN by ensuring a stable administration of sufficient calories and protein, especially in the first 2 weeks of life, implementing breast milk fortification, covering energy and protein deficits due to critical illness, and increasing feeding volumes as per the latest guidelines. The adoption of universal protocol for nutrition and growth of VPN is essential and will enable better monitoring of long-term outcomes for this population.

Pegylated-polycaprolactone nano-sized drug delivery platforms loaded with biocompatible silver(i) complexes for anticancer therapeutics.

Cytotoxic potential of Ag(i) coordination compounds against cancer cells is widely recognized, but their frequently low water solubility and potential adverse interactions of Ag(i) ions in biological media require their incorporation into suitable platforms to ensure effective transport and delivery at target sites. Herein, we developed and evaluated the in vitro cytotoxic activity of a biodegradable copolymer-based nano-sized drug delivery system for three cytotoxically active and lipophillic Ag(i) compounds. In particular, polymer-based nanoparticles of the newly synthesized amphiphilic methoxy-poly(ethylene glycol)-poly(caprolactone) (mPEG-PCL) copolymer were prepared as carriers for [Ag(dmp2SH)(PPh3)2]NO3 (1), [Ag(dmp2SH)(xantphos)]NO3 (2) and [Ag(dmp2S)(xantphos)] (3) (dmP2SH = 4,6-dimethylpyrimidine-2-thiol, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene) which exhibit high cytotoxicity against HeLa cancer cells, while they maintain low toxicity against HDFa normal cells. Taking advantage of the favorable donor-acceptor Lewis acid-base and electrostatic interactions between functional groups of 1-3 and mPEG-PCL copolymer, the formation of [X]@mPEG-PCL (X = 1,2,3) nanoparticles with nearly spherical shape was achieved. Satisfactory loading capacities and encapsulation efficiencies were obtained (13-15% and 80-88%, respectively). Differences in their mean size diameters were observed, revealing a dependence on the individual structural characteristics of the Ag(i) compounds. In vitro release profiles of the nanoparticles showed an initial burst stage, followed by a prolonged release stage extending over 15 days, with their release rates being determined by the mean size of the nanoparticles, as well as the type and crystallinity of the encapsulated Ag(i) compounds. In vitro cytotoxicity studies revealed an increased cytotoxic activity of compounds 1-3 after their encapsulation in mPEG-PCL copolymer against HeLa cells, with the actual concentrations of the loaded compounds responsible for the inhibition of cell viability being reduced by 8 times compared to the compounds in free form. Therefore, the current drug delivery system improves the pharmacokinetic properties of the three cytotoxic and biocompatible Ag(i) compounds, and may be beneficial for future in vivo anticancer treatment.

Induced differentiation and molecular characterization of monocytes-derived multipotential cells generated from commonly discarded leukapheresis filters.

Monocyte-derived multipotential cells (MOMCs) are a subpopulation of monocytes that appear to be capable of differentiating into many cell populations, thus MOMCs can be an ideal autologous transplantable cell source for regenerative medicine. In this study, we generated MOMCs from leukapheresis filters, evaluated their ability to differentiate to endothelium and osteocytes and performed their molecular characterization. For this purpose, leukapheresis filters were collected from a hospital blood donation department and used for leukocytes isolation. The isolated leukocytes were cultured in a medium supplemented with SDF-1a for MOMCs generation. We evaluated the expression of the multipotency genes ZNF217, ZNF878, ESRRB, SALL4, KLF4, SOX2, NANOG, OCT4, GAPDH, CD34 and c- MYC in MOMCs with real-time reverse transcription PCR (qRT-PCR) and the differentiation capacity of MOMCs to osteocytes and endothelium with qRT-PCR. The results suggest that MOMCs can be generated using leukocytes isolated from leukapheresis filters in the presence of SDF-1a. Furthermore, MOMCs expressed all the tested factors responsible to activate the networks of pluripotency of cells and can differentiate into endothelium and osteocytes. Therefore, the blood donors could benefit and be rewarded with the potential use of their own immune system cells for future treatment in the frame of personalized regenerative medicine.

Αn optimized, simplified and clinically approved culture system to produce, in large scale, dendritic cells capable of priming specific T cells.

Cancer immunotherapy using dendritic cells (DCs) able to induce specific immune responses to naïve T lymphocytes raises great research interest. However, the extremely complex and expensive methods used to produce DCs, combined with the limited number of autologous DCs in the circulation make any application almost impossible. Aim of the study is the development of an optimized and simplified system to easily produce in large scale cord blood-derived DCs, loaded with common tumor antigens, capable of promoting controlled Th1 immunoresponses following clinically approved maturation with vaccines. CD34+cells cultured in the presence of a cytokine cocktail in miniPERM® bioreactors and the generated DCs were matured using anti-flu vaccines. Autologous T cells plated with DCs pulsed with overlapping peptides CEA and WT1 for multiple stimulations. 200 billion of myeloid DCs were produced and matured in just 8 h in bioreactors, presenting an increased expression of the co-stimulatory molecules and also high levels of Th1 related cytokines. Upon just the 2nd stimulation, the T cells exhibited specificity following stimulation with the CEA/WT1 peptides and strong cytotoxic capacity in co-culture with a colorectal cancer (CRC)-cell line. The high produced doses of DCs, easily maturated with clinically approved agents, and capable of priming specific T cells, could potentially strengthen the further progress in DCs-mediated cancer immunotherapy field.

Intravitreal Administration Effect of Adipose-Derived Mesenchymal Stromal Cells Combined with Anti-VEGF Nanocarriers, in a Pharmaceutically Induced Animal Model of Retinal Vein Occlusion.

Antiangiogenic therapeutic agents (anti-VEGF) have contributed to the treatment of retinal vein occlusion (RVO) while mesenchymal stromal cell- (MSCs-) mediated therapies limit eye degeneration. The aim of the present study is to determine the effect of adipose-derived MSCs (ASCs) combination with nanocarriers of anti-VEGF in a pharmaceutically induced animal model of RVO. Nanoparticles (NPs) of thiolated chitosan (ThioCHI) with encapsulated anti-VEGF antibody were prepared. ASCs were isolated and genetically modified to secrete the green fluorescence GFP. Twenty-four New Zealand rabbits were divided into the I-IV equal following groups: ASCs, ASCs + nanoThioCHI-anti-VEGF, RVO, and control. For the RVO induction, groups I-III received intravitreal (iv) injections of MEK kinase inhibitor, PD0325901. Twelve days later, therapeutic regiments were administered at groups I-II while groups III-IV received BSS. Two weeks later, the retinal damage evaluated via detailed ophthalmic examinations, histological analysis of fixed retinal sections, ELISA for secreted cytokines in peripheral blood or vitreous fluid, and Q-PCR for the expression of related to the occlusion and inflammatory genes. Mild retinal edema and hemorrhages, limited retinal detachment, and vasculature attenuation were observed in groups I and II compared with the pathological symptoms of group III which presented a totally disorganized retinal structure, following of positive immunostaining for neovascularization and related to RVO markers. Important reduction of the high secreted levels of inflammatory cytokines was quantified in groups I and II vitreous fluid, while the expression of the RVO-related and inflammatory genes has been significantly decreased especially in group II. GFP+ ASCs, capable of being differentiated towards neural progenitors, detected in dissociated retina tissues of group II presenting their attachment to damaged area. Conclusively, a stem cell-based therapy for RVO is proposed, accompanied by sustained release of anti-VEGF, in order to combine the paracrine action of ASCs and the progressive reduction of neovascularization.

Effect of Long-Term Cryopreservation on the Stemness of Stem Cells of Apical Papilla.

Stem cells of apical papilla (SCAPs) are considered a subpopulation of dental stem cells with unique properties. They originate from a developing tissue, the apical papilla of developing teeth, a characteristic that enhances their stemness. Banking of these stem cells can offer a source of dental stem cells for future regenerative therapies. Until now, only the effect of six months' cryopreservation on SCAPs has been studied. In this study, the long-term (19 months) effect of cryopreservation on SCAPs was examined by means of estimation of their differentiation's capacity, flow cytometry immunophenotypical characterization, and molecular characterization of the main transcriptional factors that coincide with pluripotency. As was indicated from our results, 19-month cryopreservation of SCAPs did not affect negatively their stemness; since no significant difference was observed on their typical fibroblast-like morphology, they retained their differentiation capacity, and no discrepancies were found either on immunophenotypical level or molecular level.

Poly(l-Lactic Acid)-co-poly(Butylene Adipate) New Block Copolymers for the Preparation of Drug-Loaded Long Acting Injectable Microparticles.

The present study evaluates the use of newly synthesized poly(l-lactic acid)-co-poly(butylene adipate) (PLA/PBAd) block copolymers as microcarriers for the preparation of aripiprazole (ARI)-loaded long acting injectable (LAI) formulations. The effect of various PLA to PBAd ratios (95/5, 90/10, 75/25 and 50/50 w/w) on the enzymatic hydrolysis of the copolymers showed increasing erosion rates by increasing the PBAd content, while cytotoxicity studies revealed non-toxicity for all prepared biomaterials. SEM images showed the formation of well-shaped, spherical MPs with a smooth exterior surface and no particle's agglomeration, while DSC and pXRD data revealed that the presence of PBAd in the copolymers favors the amorphization of ARI. FTIR spectroscopy showed the formation of new ester bonds between the PLA and PBAd parts, while analysis of the MP formulations showed no molecular drug-polyester matrix interactions. In vitro dissolution studies suggested a highly tunable biphasic extended release, for up to 30 days, indicating the potential of the synthesized copolymers to act as promising LAI formulations, which will maintain a continuous therapeutic level for an extended time period. Lastly, several empirical and mechanistic models were also tested, with respect to their ability to fit the experimental release data.

"Aggressive" Feeding of Very Preterm Neonates and Body Mass Index at School Age.

INTRODUCTION: The effects of "aggressive" neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our "aggressive" nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. MATERIALS AND METHODS: Eighty four VPN, who received "aggressive" nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180-210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. RESULTS: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. CONCLUSIONS: "Aggressive" and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.

Gastric Volume Changes in Preterm Neonates during Intermittent and Continuous Feeding-GRV and Feeding Mode in Preterm Neonates.

Background: We aimed to evaluate gastric volume changes during intermittent milk feeds (IMF) and continuous milk feeds (CMF) in very premature neonates (VPN), with gastric residual volume (GRV) based on antral cross-sectional area (ACSA) measurements and to examine if there were differences in GRV between the two feeding methods. Methods: A randomized prospective clinical trial with crossover design was conducted in 31 preterm neonates (gestational age < 30 weeks). Gastric volume was assessed twice in each neonate (during IMF and CMF feeding), at 7 specific time points during a 2-h observation period by measuring ACSA changes via the ultrasound (U/S) method. Results: There was a significantly different pattern of gastric volume changes between the two feeding methods. GRV, expressed as the median percentage of ACSA measurement at 120 min relative to the higher ACSA measurement during IMF, was found to be 3% (range 0-25%) for IMF and 50% (range 15-80%) for CMF. Neonates fed with IMF had a shorter mean gastric emptying time compared to those fed with CMF (p = 0.0032). No signs of feeding intolerance were recorded in either group during the period of observation. Conclusions: Our results showed that gastric volume changes and gastric emptying time in VPN, based on ACSA measurement changes, depend on the milk feeding method. No gastrointestinal complications/adverse events were noted with GRV up to 80% with CMF.

Evaluation of Clinical and Histological Outcomes of Adipose-Derived Mesenchymal Stem Cells in a Rabbit Corneal Alkali Burn Model.

To assess effects of adipose-derived mesenchymal stem cells (AMSCs) in corneal alkali injuries in an experimental animal model. Twenty white New Zealand rabbits were included in the study. The animal models were randomly divided into 2 groups. Rabbits in the AMSC group (n = 10) received an intrastromal, a subconjunctival injection, and topical instillation of 0.5 ml totally of phosphate-buffered saline (PBS) containing 2 × 106 AMSCs. In the control group (n = 10), rabbits received only 0.5 ml of PBS using the same methods. A masked investigator measured the corneal sensation, anterior chamber Inflammation (ACI), and conjunctival congestion. Additionally, a blind histological and immunohistochemical evaluation was made. In the AMSC group, the central corneal sensation was increased whereas ACI and conjunctival congestion were reduced compared to the control group in the 28 days of follow-up (p < 0.05). A statistically significant difference (p < 0.05) was noted between the two groups as recorded in the above parameters. Histological analysis showed that pathological vascularization was markedly reduced in the AMSC group which was consistent with the absence of factor VIII in the immunohistochemistry sections. There is a trend towards improved clinical outcomes including corneal sensation as well as acceleration in the restoration of normal corneal architecture in corneal alkali burns treated with AMSCs, results that support the need for further research in the field.

Innovative Skin Product Emulsions with Enhanced Antioxidant, Antimicrobial and UV Protection Properties Containing Nanoparticles of Pure and Modified Chitosan with Encapsulated Fresh Pomegranate Juice.

In the present study, a chitosan (CS) derivative with the 2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SDAEM) zwitterionic monomer was prepared through chemical modification. The successful synthesis of CS-SDAEM was confirmed by Fourier-transform Infrared (FTIR) and Nuclear Magnetic Resonance (1H-NMR) spectroscopies. Its crystallinity was studied by X-ray Diffraction (XRD), while in vitro cytotoxicity and cell viability assays established its biocompatibility. Filtered fresh pomegranate juice (PJ) was loaded in nanoparticles of neat CS and its derivative via ionic gelation method. Dynamic Light Scattering (DLS) revealed nanoparticles sizes varying between 426 nm and 4.5 µm, indicating a size-dependence on the polymer concentration used during encapsulation. High-performance liquid chromatography coupled with photodiode array and electrospray ionization mass spectrometry detection (LC-PDA-ESI/MS) revealed that PJ active compounds were successfully and in sufficient amounts encapsulated in the nanoparticles interior, whereas XRD indicated a crystalline structure alteration after nanoencapsulation. The resulted PJ-loaded nanoparticles were further utilized for the preparation of innovative O/W cosmetic emulsions. All produced emulsions exhibited good pH and viscosity stability for up to 90 days, while the sun protection factor (SPF) was enhanced due to the presence of the PJ. Enhanced antioxidant and antimicrobial properties due to the phenolic compounds of PJ were also observed.

Caffeine and Gastric Emptying Time in Very Preterm Neonates.

BACKGROUND: Caffeine has been commonly used for prevention and treatment of apnea-related symptoms in premature infants. However, its side effects have not been thoroughly studied. We investigated whether caffeine affects gastric motility in very-preterm (VP) neonates. METHODS: The study is a randomized crossover clinical trial. Twenty-two neonates with mean birth weight (BW) (standard deviation-SD) 1077 (229) g and mean gestational age (GA) (SD) 28.6 (2.1) weeks were recruited. Each neonate had its gastric emptying time checked twice with ultrasound assessment of changes in antral cross sectional area (ACSA). All neonates were sequentially allocated to the caffeine group (A) and the control group (B). Complications from the gastrointestinal tract were documented throughout the study. RESULTS: Statistically significant difference was found with regards to the gastric emptying time [median, (range)] between caffeine and control group (p = 0.040). Additionally, in the neonates with BW 1000-1500 g and GA ≥ 28 weeks, the gastric emptying time (minutes) was significantly longer during caffeine treatment [44.5 (36-68.2)] and [40 (34.5-66.5)] respectively, as compared to the gastric emptying time during no caffeine treatment [27 (24.2-30)] (p = 0.002) and [27 (24.5-30)] (p = 0.001). The incidence of gastrointestinal (GI) complications was significantly greater in neonates receiving caffeine [6 (27.%)] as compared with those without caffeine treatment [1 (4.6%)] (p = 0.039). CONCLUSIONS: During caffeine treatment, a significantly delayed gastric emptying time was noted in all study neonates, especially in these with BW 1000-1500 g and those with GA ≥ 28 weeks. Further larger studies are necessary in order to confirm this interesting finding.

The Antiangiogenic Properties of Adipose-Derived Mesenchymal Stem/Stromal Cells in Corneal Neovascularization in a Rabbit Model.

The purpose was to study the anti-angiogenic effect of adipose-derived mesenchymal stem/stromal cells (ADMSCs) on experimentally induced corneal injuries. Corneal neovascularization (NV) was induced by incising and subsequently suturing the corneal surface in 32 New Zealand rabbits. Following suturing, the rabbits were randomly allocated into 2 groups, and received either phosphate-buffered saline (PBS) (control) or ADMSCs, both administered via three different routes. Digital images of the cornea were obtained two weeks post-incision to measure the area of neovascularized cornea. Tumor necrosis factor (TNF) was immunohistochemically assessed in the both groups. The corneal tissue was evaluated for vascular endothelial growth factor (VEGF). The extent of corneal NV in all eyes was assessed photographically by an independent observer. Fourteen days after the incisions, the degree of corneal NV was substantially decreased in the ADMSC-treated group (1.87 ± 0.9 mm2, 1.4 % ± 0.67 % of corneal surface) compared to the control and PBS-treated group (4.66 ± 1.74 mm2, 3.51 % ± 1.31 %, p < 0.001). ADMSCs significantly decreased injury-induced corneal NV in New Zealand rabbits two weeks post-treatment. This strategy has potential for use in the control of corneal NV in vivo.

Very preterm neonates receiving "aggressive" nutrition and early nCPAP had similar long-term respiratory outcomes as term neonates.

BACKROUND: The impact of the consistent implementation of "aggressive" nutrition by means of intensive early neonatal nutritional support up to 40-44 weeks postmenstrual age and the use of nasal continuous positive airway pressure (nCPAP) within the first hour of life on the respiratory function of very premature neonates (VPN) at school age is unclear. METHOD: Respiratory function was evaluated in 108 VPN and 70 term controls. Growth, frequency of lower respiratory tract infections, re-hospitalization, and spirometry were recorded up to 8-10 years of age. Comparison was carried out between the two study groups. RESULTS: There was no significant difference in forced expiratory volume in 1 s and forced vital capacity at 8 years of age, and also in lower respiratory tract infections and re-hospitalization due to them, up to 8 years of age between preterm and term neonates. No significant difference was found in spirometry measurements neither between premature neonates with and without BPD nor between the two subgroups of preterms and term neonates. CONCLUSION: "Aggressive" nutrition, persistent nCPAP use, and their impact on early postnatal growth probably positively affect the respiratory function of our study population. These very encouraging results need to be confirmed by larger studies.

Umbilical Venous Catheters and Peripherally Inserted Central Catheters: Are They Equally Safe in VLBW Infants? A Non-Randomized Single Center Study.

Background and Objective: Peripherally inserted central catheters (PICC) and umbilical venous catheters (UVC) are frequently used for vascular access in neonatal intensive care units (NICUs). While there is a significant need for these devices for critically ill neonates, there are many complications associated with their use. We aimed at investigating the incidence of UVC and PICC complications in very low birth weight (VLBW) infants. Materials and Methods: This is an observational study performed with neonates of the tertiary General Hospital of Piraeus, Greece, during an 18 month-period. Seventy-one neonates were recruited and divided into two groups: 34 neonates with PICC and 37 neonates with UVC. We recorded: Catheter dwell time, the causes of catheter removal, other complications, infections, and catheter tip colonization rates. Results: No significant statistical differences were noticed between the 2 study groups with regards to demographic characteristics, causes for catheter removal, catheter indwelling time or the incidence of nosocomial infection. Eleven UVC tips and no PICC tips were proved colonized (p = 0.001) following catheter removal. Conclusions: The incidence of complications associated with the use of UVCs and PICCs in VLBW infants did not significantly differ in our study. Their use seems to be equally safe. Further studies, with larger samples, are necessary to confirm our results.

Composite Membranes of Poly(ε-caprolactone) with Bisphosphonate-Loaded Bioactive Glasses for Potential Bone Tissue Engineering Applications.

Poly(ε-caprolactone) (PCL) is a bioresorbable synthetic polyester with numerous biomedical applications. PCL membranes show great potential in guided tissue regeneration because they are biocompatible, occlusive and space maintaining, but lack osteoconductivity. Therefore, two different types of mesoporous bioactive glasses (SiO2-CaO-P2O5 and SiO2-SrO-P2O5) were synthesized and incorporated in PCL thin membranes by spin coating. To enhance the osteogenic effect of resulting membranes, the bioglasses were loaded with the bisphosphonate drug ibandronate prior to their incorporation in the polymeric matrix. The effect of the composition of the bioglasses as well as the presence of absorbed ibandronate on the physicochemical, cell attachment and differentiation properties of the PCL membranes was evaluated. Both fillers led to a decrease of the crystallinity of PCL, along with an increase in its hydrophilicity and a noticeable increase in its bioactivity. Bioactivity was further increased in the presence of a Sr substituted bioglass loaded with ibandronate. The membranes exhibited excellent biocompatibility upon estimation of their cytotoxicity on Wharton's Jelly Mesenchymal Stromal Cells (WJ-SCs), while they presented higher osteogenic potential in comparison with neat PCL after WJ-SCs induced differentiation towards bone cells, which was enhanced by a possible synergistic effect of Sr and ibandronate.

Paclitaxel Magnetic Core⁻Shell Nanoparticles Based on Poly(lactic acid) Semitelechelic Novel Block Copolymers for Combined Hyperthermia and Chemotherapy Treatment of Cancer.

Magnetic hybrid inorganic/organic nanocarriers are promising alternatives for targeted cancer treatment. The present study evaluates the preparation of manganese ferrite magnetic nanoparticles (MnFe2O4 MNPs) encapsulated within Paclitaxel (PTX) loaded thioether-containing ω-hydroxyacid-co-poly(d,l-lactic acid) (TEHA-co-PDLLA) polymeric nanoparticles, for the combined hyperthermia and chemotherapy treatment of cancer. Initially, TEHA-co-PDLLA semitelechelic block copolymers were synthesized and characterized by 1H-NMR, FTIR, DSC, and XRD. FTIR analysis showed the formation of an ester bond between the two compounds, while DSC and XRD analysis showed that the prepared copolymers were amorphous. MnFe2O4 MNPs of relatively small crystallite size (12 nm) and moderate saturation magnetization (64 emu·g-1) were solvothermally synthesized in the sole presence of octadecylamine (ODA). PTX was amorphously dispersed within the polymeric matrix using emulsification/solvent evaporation method. Scanning electron microscopy along with energy-dispersive X-ray spectroscopy and transmission electron microscopy showed that the MnFe2O4 nanoparticles were effectively encapsulated within the drug-loaded polymeric nanoparticles. Dynamic light scattering measurements showed that the prepared nanoparticles had an average particle size of less than 160 nm with satisfactory yield and encapsulation efficiency. Diphasic PTX in vitro release over 18 days was observed while PTX dissolution rate was mainly controlled by the TEHA content. Finally, hyperthermia measurements and cytotoxicity studies were performed to evaluate the magnetic response, as well as the anticancer activity and the biocompatibility of the prepared nanocarriers.