Search Results (69)

Tissue-engineered biocompatible scaffolds could mimic the extracellular matrix structure for cell adhesion and proliferation; however, patients suffer from large volume implantation. In this study, a thermal sensitive shape memory polyurethane porous 3D scaffold based on poly(ε-caprolactone) and poly(ethylene glycol adipate) was developed, utilizing the water-splitting property of aliphatic hexamethylene diisocyanate (HDI) to crosslink rigid segments during the polymerization process. The chemical structure, microstructure, and morphology, as well as mechanical strength, of the scaffolds were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), a scanning electron microscope (SEM), and tensile tests. The results show that gas foaming action caused by the release of CO₂ occurred simultaneously in the reactive process, resulting in the interconnective porous structure of the PU scaffolds with a porosity of over 70% and pore sizes from 100 μm to 800 μm. Additionally, after programming to a temporary shape, the scaffolds could recover to their initial shapes and could be programmed into various shapes according to different defects. These smart shape-changeable scaffolds with high porosity and good physio-chemical properties are a promising material for minimally invasive tissue engineering. Full article

Nanocomposites prepared with a terpolymer of poly(L–lactide) (PLLA)–poly(ε–caprolactone) (PCL)–poly(ethylene glycol) (PEG) and partially oxidized carbon nanotubes (CNTs_po) were synthesized and characterized to evaluate their ability to act as an effective nanocarrier of the anticancer drug methotrexate. The homopolymers of PLLA and PCL were synthesized through ring-opening polymerization (ROP) and characterized through gel permeation chromatography (GPC). The PLLA–PCL–PEG terpolymers were synthesized through a four-step chemical route using oxalyl chloride as a linker agent and analyzed with ¹H–NMR, ¹³C–NMR, and FTIR spectroscopies. Additionally, the nanocomposites were characterized through FTIR, and X-ray photoelectron spectroscopy (XPS), as well as the differential scanning calorimetry (DSC) technique. XPS analysis revealed that PLLA–PCL–PEG terpolymer chains are grafted onto CNTs_po. Moreover, evaluations through FTIR and DSC strongly suggest that the PCL-rich domains are preferentially oriented toward CNTs_po. The release tests exhibited a “burst effect” profile, which was more evident in the terpolymers than in the nanocomposites. Five models were used to assess methotrexate’s in vitro release. For the nanocomposites, the best fit to the experimental data was obtained using the first-order model, whereas the results obtained from the Korsmeyer–Peppas model indicated that Fickian diffusion drives methotrexate’s release. Full article

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy. Full article

Bone tissue exhibits self-healing properties; however, not all defects can be repaired without surgical intervention. Bone tissue engineering offers artificial scaffolds, which can act as a temporary matrix for bone regeneration. The aim of this study was to manufacture scaffolds made of poly(lactic acid), poly(ε-caprolactone), poly(propylene fumarate), and poly(ethylene glycol) modified with bioglass, beta tricalcium phosphate (TCP), and/or wollastonite (W) particles. The scaffolds were fabricated using a gel-casting method and observed with optical and scanning electron microscopes. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), wettability, and degradation tests were conducted. The highest content of TCP without W in the composition caused the highest hydrophilicity (water contact angle of 61.9 ± 6.3°), the fastest degradation rate (7% mass loss within 28 days), moderate ability to precipitate CaP after incubation in PBS, and no cytotoxicity for L929 cells. The highest content of W without TCP caused the highest hydrophobicity (water contact angle of 83.4 ± 1.7°), the lowest thermal stability, slower degradation (3% mass loss within 28 days), and did not evoke CaP precipitation. Moreover, some signs of cytotoxicity on day 1 were observed. The samples with both TCP and W showed moderate properties and the best cytocompatibility on day 4. Interestingly, they were covered with typical cauliflower-like hydroxyapatite deposits after incubation in phosphate-buffered saline (PBS), which might be a sign of their excellent bioactivity. Full article

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a “burst release”. The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists. Full article

Bone tissue is one of the most transplanted tissues. The ageing population and bone diseases are the main causes of the growing need for novel treatments offered by bone tissue engineering. Three-dimensional (3D) scaffolds, as artificial structures that fulfil certain characteristics, can be used as a temporary matrix for bone regeneration. In this study, we aimed to fabricate 3D porous polymer scaffolds functionalized with tricalcium phosphate (TCP) particles for applications in bone tissue regeneration. Different combinations of poly(lactic acid) (PLA), poly(ethylene glycol) (PEG with molecular weight of 600 or 2000 Da) and poly(ε-caprolactone) (PCL) with TCP were blended by a gel-casting method combined with rapid heating. Porous composite scaffolds with pore sizes from 100 to 1500 µm were obtained. ATR-FTIR, DSC, and wettability tests were performed to study scaffold composition, thermal properties, and hydrophilicity, respectively. The samples were observed with the use of optical and scanning electron microscopes. The addition of PCL to PLA increased the hydrophobicity of the composite scaffolds and reduced their susceptibility to degradation, whereas the addition of PEG increased the hydrophilicity and degradation rates but concomitantly resulted in enhanced creation of rounded mineral deposits. The scaffolds were not cytotoxic according to an indirect test in L929 fibroblasts, and they supported adhesion and growth of MG-63 cells when cultured in direct contact. Full article

Glioblastoma (GBM) is the most common and deadly primary malignant brain tumor. Current therapies are insufficient, and survival for individuals diagnosed with GBM is limited to a few months. New GBM treatments are urgent. Polymeric nanoparticles (PNs) can increase the circulation time of a drug in the brain capillaries. Polymersomes (PMs) are PNs that have been described as having attractive characteristics, mainly due to their stability, prolonged circulation period, biodegradability, their ability to sustain the release of drugs, and the possibility of surface functionalization. In this work, a poly(ethylene glycol)-ε-caprolactone (PEG-PCL) copolymer was synthesized and PMs were prepared and loaded with an hydrolytic instable compound, previously synthesized by our research team, the 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (XGAc), with promising cytotoxicity on glioblastoma cells (U-373 MG) but also on healthy cerebral endothelial cells (hCMEC/D3). The prepared PMs were spherical particles with uniform morphology and similar sizes (mean diameter of 200 nm) and were stable in aqueous suspension. The encapsulation of XGAc in PMs (80% encapsulation efficacy) protected the healthy endothelial cells from the cytotoxic effects of this compound, while maintaining cytotoxicity for the glioblastoma cell line U-373 MG. Our studies also showed that the prepared PMs can efficiently release XGAc at intratumoral pHs. Full article

Novel polyurethane-based materials have been synthesized by a two-step process using poly(ε–caprolactone) diol (PCL) and 1,3–propanediol/starch (PDO/ST) systems as chain extenders/cross-linkers and 1,6–hexamethylane diisocyante (HDI) as a potential material for bone tissue replacement or bone cements. A poly(ethylene glycol)/starch (PEG/ST) system has been applied as a form-stable phase change material (PCM) to decrease the maximum setting temperature, while hydroxyapatite (HAp) has been used as a bioactive nanofiller. FTIR and SEM-EDX analyses were performed to investigate the structure, surface morphology, and thermal properties of the obtained polyurethanes. FTIR spectroscopy confirmed the chemical structure of the synthesized polyurethanes. SEM-EDX analysis confirmed the incorporation of starch/hydroxyapatite into the polyurethane matrix. Modification with PCMs based on PEG or PEG/starch systems allowed for a decrease in the maximum setting temperature of PUs from 6 to 7.6 °C, depending on the type of PCM used. Thus, the obtained polyurethanes show a good energy storage effect and a good application potential for the synthesis of multifunctional bioactive materials for future use as bone cements. Full article

This study investigated the effect of the Joncryl concentration on the properties of polylactide/poly(ε-caprolactone) (PLA/PCL) and PLA/poly(ethylene glycol) (PEG) blends. The addition of Joncryl influenced the properties of both PLA-based blends. In the blend of PLA/PCL blends, the addition of Joncryl reduced the size of PCL droplets, which implies the compatibility of the two phases, while PLA/PEG blends showed a co-continuous type of morphology at 0.1% and 0.3 wt.% of Joncryl loading. The crystallinity of PCL and PEG was studied on both PLA/PCL and PLA/PEG blend systems. In both scenarios, the crystallinity of the blends decreased upon the addition of Joncryl. Thermal stabilities were shown to depend on the addition of Joncryl. The toughness increased when 0.5 wt.% of Joncryl was added to both systems. However, the stiffness of PLA/PCL decreased, while the stiffness of PLA/PEG increased with the increasing concentration of Joncryl. This study provides new insight into the effect of chain extenders on the compatibility of PLA-based blends. Full article

Polymeric micelles are promising carriers for the delivery of poorly water-soluble drugs, providing enhanced drug solubility, blood circulation times, and bioavailability. Nevertheless, the storage and long-term stability of micelles in solution present challenges requiring the lyophilization and storage of formulations in the solid state, with reconstitution immediately prior to application. Therefore, it is important to understand the effects of lyophilization/reconstitution on micelles, particularly their drug-loaded counterparts. Herein, we investigated the use of β-cyclodextrin (β-CD) as a cryoprotectant for the lyophilization/reconstitution of a library of poly(ethylene glycol-b-ε-caprolactone) (PEG-b-PCL) copolymer micelles and their drug-loaded counterparts, as well as the effect of the physiochemical properties of different drugs (phloretin and gossypol). The critical aggregation concentration (CAC) of the copolymers decreased with increasing weight fraction of the PCL block (f_PCL), plateauing at ~1 mg/L when the f_PCL was >0.45. The blank (empty) and drug-loaded micelles were lyophilized/reconstituted in the absence and presence of β-CD (9% w/w) and analyzed via dynamic light scattering (DLS) and synchrotron small-angle X-ray scattering (SAXS) to assess for changes in aggregate size (hydrodynamic diameter, D_h) and morphology, respectively. Regardless of the PEG-b-PCL copolymer or the use of β-CD, the blank micelles displayed poor redispersibility (<10% relative to the initial concentration), while the fraction that redispersed displayed similar D_h to the as-prepared micelles, increasing in D_h as the f_PCL of the PEG-b-PCL copolymer increased. While most blank micelles displayed discrete morphologies, the addition of β-CD or lyophilization/reconstitution generally resulted in the formation of poorly defined aggregates. Similar results were also obtained for drug-loaded micelles, with the exception of several that retained their primary morphology following lyophilization/reconstitution, although no obvious trends were noted between the microstructure of the copolymers or the physicochemical properties of the drugs and their successful redispersion. Full article

Aliphatic and aromatic polyesters of hydroxycarboxylic acids are characterized not only by biodegradability, but also by biocompatibility and inertness, which makes them suitable for use in different applications. Polyesters with high enzymatic hydrolysis capacity include poly(lactic acid), poly(ε-caprolactone), poly(butylene succinate) and poly(butylene adipate-co-terephthalate), poly(butylene succinate-co-adipate). At the same time, poly(lactic acid) is the most durable, widespread, and cheap polyester from this series. However, it has a number of drawbacks, such as high brittleness, narrow temperature-viscosity processing range, and limited biodegradability. Three main approaches are known for poly(lactic acid) modification: incorporation of dispersed particles or low molecular weight and oligomeric substances, copolymerization with other polymers, and blending with other polymers. The review includes an analysis of experimental works devoted to developing mixtures based on poly(lactic acid) and other polymers. Regularities in the formation of the structure of such systems and the possibility of controlling the properties of poly(lactic acid) are considered. Full article

The aim of this study was to develop an innovative, dual-stimuli-responsive smart hydrogel local drug delivery system (LDDS), potentially useful as an injectable simultaneous chemotherapy and magnetic hyperthermia (MHT) antitumor treatment device. The hydrogels were based on a biocompatible and biodegradable poly(ε-caprolactone-co-rac-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-rac-lactide) (PCLA-PEG-PCLA, PCLA) triblock copolymer, synthesized via ring-opening polymerization (ROP) in the presence of a zirconium(IV) acetylacetonate (Zr(acac)₄) catalyst. The PCLA copolymers were successfully synthesized and characterized using NMR and GPC techniques. Furthermore, the gel-forming and rheological properties of the resulting hydrogels were thoroughly investigated, and the optimal synthesis conditions were determined. The coprecipitation method was applied to create magnetic iron oxide nanoparticles (MIONs) with a low diameter and a narrow size distribution. The magnetic properties of the MIONs were close to superparamagnetic upon TEM, DLS, and VSM analysis. The particle suspension placed in an alternating magnetic field (AMF) of the appropriate parameters showed a rapid increase in temperature to the values desired for hyperthermia. The MIONs/hydrogel matrices were evaluated for paclitaxel (PTX) release in vitro. The release was prolonged and well controlled, displaying close to zero-order kinetics; the drug release mechanism was found to be anomalous. Furthermore, it was found that the simulated hyperthermia conditions had no effect on the release kinetics. As a result, the synthesized smart hydrogels were discovered to be a promising antitumor LDDS, allowing simultaneous chemotherapy and hyperthermia treatment. Full article

Quercetin is a hydrophobic molecule with short blood circulation times and instability. The development of a nano-delivery system formulation of quercetin may increase its bioavailability, resulting in greater tumor suppressing effects. Triblock ABA type polycaprolactone-polyethylenglycol- polycaprolactone (PCL-PEG-PCL) copolymers have been synthetized using ring-opening polymerization of caprolactone from PEG diol. The copolymers were characterized by nuclear magnetic resonance (NMR), diffusion-ordered NMR spectroscopy (DOSY), and gel permeation chromatography (GPC). The triblock copolymers self-assembled in water forming micelles consisting of a core of biodegradable polycaprolactone (PCL) and a corona of polyethylenglycol (PEG). The core-shell PCL-PEG-PCL nanoparticles were able to incorporate quercetin into the core. They were characterized by dynamic light scattering (DLS) and NMR. The cellular uptake efficiency of human colorectal carcinoma cells was quantitatively determined by flow cytometry using nanoparticles loaded with Nile Red as hydrophobic model drug. The cytotoxic effect of quercetin-loaded nanoparticles was evaluated on HCT 116 cells, showing promising results. Full article

Although vaccination is still considered to be the cornerstone of public health care, the increase in vaccination coverage has stagnated for many diseases. Most of these vaccines require two or three doses to be administered across several months or years. Single-injection vaccine formulations are an effective method to overcome the logistical barrier to immunization that is posed by these multiple-injection schedules. Here, we developed subcutaneously (s.c.) injectable microspheres with a sustained release of the model antigen bovine serum albumin (BSA). The microspheres were composed of blends of two novel biodegradable multi-block copolymers consisting of amorphous, hydrophilic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) blocks and semi-crystalline poly(dioxanone) (PDO) blocks of different block sizes. In vitro studies demonstrated that the release of BSA could be tailored over a period of approximately four to nine weeks by changing the blend ratio of both polymers. Moreover, it was found that BSA remained structurally intact during release. Microspheres exhibiting sustained release of BSA for six weeks were selected for the in vivo study in mice. The induced BSA-specific IgG antibody titers increased up to four weeks after administration and were of the same magnitude as found in mice that received a priming and a booster dose of BSA in phosphate-buffered saline (PBS). Determination of the BSA concentration in plasma showed that in vivo release probably took place up to at least four weeks, although plasma concentrations peaked already one week after administration. The sustained-release microspheres might be a viable alternative to the conventional prime-boost immunization schedule, but a clinically relevant antigen should be incorporated to assess the full potential of these microspheres in practice. Full article

Cancer is still one of the major diseases worldwide. The discovery of new drugs and the improvement of existing ones is one of the areas of priority in the fight against cancer. Dioxadet ([5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol) represents one of the promising 1,3,5-triazine derivatives and has cytostatic activity towards ovarian cancer. In this study, we first report the development of dioxadet-bearing nanomedicines based on block-copolymers of poly(ethylene glycol) monomethyl ether (mPEG) and poly(D,L-lactic acid) (PLA)/poly(ε-caprolactone) (PCL) and then conduct an investigation into their characteristics and properties. The preparation of narrow-sized nanoparticles with a hydrodynamic diameter of 100–120 nm was optimized using a nanoprecipitation approach. Thoughtful optimization of the preparation of nanomedicines was carried out through adjustments to the polymer’s molecular weight, the pH of the aqueous medium used for nanoprecipitation, the initial drug amount in respect to the polymer, and polymer concentration in the organic phase. Under optimized conditions, spherical-shaped nanomedicines with a hydrodynamic diameter of up to 230 nm (PDI < 0.2) containing up to 592 ± 22 μg of dioxadet per mg of polymer nanoparticles were prepared. Study of the drug’s release in a model medium revealed the release up to 64% and 46% of the drug after 8 days for mPEG-b-PLA and mPEG-b-PCL, respectively. Deep analysis of the release mechanisms was carried out with the use of a number of mathematical models. The developed nanoparticles were non-toxic towards both normal (CHO-K1) and cancer (A2780 and SK-OV-3) ovarian cells. A cell cycle study revealed lesser toxicity of nanomedicines towards normal cells and increased toxicity towards cancer cells. The IC₅₀ values determined for dioxadet nanoformulations were in the range of 0.47–4.98 μg/mL for cancer cells, which is close to the free drug’s efficacy (2.60–4.14 μg/mL). The highest cytotoxic effect was found for dioxadet loaded to mPEG-b-PCL nanoparticles. Full article