Bioresorbable Nonwoven Patches as Taxane Delivery Systems for Prostate Cancer Treatment.

Prostate cancer is the second most common cancer in males. In the case of locally advanced prostate cancer radical prostatectomy is one of the first-line therapy. However, recurrence after resection of the tumor can appear. Drug-eluting bioresorbable implants acting locally in the area of the tumor or the resection margins, that reduce the risk of recurrence would be advantageous. Electrospinning offers many benefits in terms of local delivery so fiber-forming polyesters and polyestercarbonates which are suitable to be drug-loaded were used in the study to obtain CTX or DTX-loaded electrospun patches for local delivery. After a fast verification step, patches based on the blend of poly(glycolide-ε-caprolactone) and poly(lactide-glycolide) as well as patches obtained with poly(lactide-glycolide- ε-caprolactone) were chosen for long-term study. After three months, 60% of the drug was released from (PGCL/PLGA) + CTX and it was selected for final, anticancer activity analysis with the use of PC-3 and DU145 cells to establish its therapeutic potential. CTX-loaded patches reduced cell growth to 53% and 31% respectively, as compared to drug-free patches. Extracts from drug-free patches showed excellent biocompatibility with the PC-3 cell line. Cabazitaxel-loaded bioresorbable patches are a promising drug delivery system for prostate cancer therapy.

Dual-jet electrospun PDLGA/PCU nonwovens as promising mesh implant materials with controlled release of sirolimus and diclofenac.

Dual-jet electrospinning was employed to produce two-component, partially degradable drug releasing nonwovens with interlacing of poly(D,L-lactide-co-glycolide) (PDLGA) and different poly(carbonate urethanes) (PCUs). Diclofenac sodium and sirolimus were released simultaneously from the copolyester carrier. The research focused on determining of release profiles of drugs, depending on the hydrophilicity of introduced PCU nanofibers. The influence of drugs incorporation on the hydrolytic degradation of the PDLGA and mechanical properties of nonwovens was also studied. Evaluation for interaction with cells in vitro was investigated on a fibroblast cell line in cytotoxicity and surface adhesion tests. Significant changes in drugs release rate, depending on the applied PCU were observed. It was also noticed, that hydrophilicity of drugs significantly influenced the hydrolytic degradation mechanism and surface erosion of the PDLGA, as well as the tensile strength of nonwovens. Tests carried out on cells in an in vitro experiment showed that introduction of sirolimus caused a slight reduction in the viability of fibroblasts as well as a strong limitation in their capability to colonize the surface of fibers. Due to improvement of mechanical strength and the ability to controlled drugs release, the obtained material may be considered as prospect surgical mesh implant in the treatment of hernia.

Two-Step Geometry Design Method, Numerical Simulations and Experimental Studies of Bioresorbable Stents.

The stent-implantation process during angioplasty procedures usually involves clamping the stent onto a catheter to a size that allows delivery to the place inside the artery. Finding the right geometrical form of the stent to ensure good functionality in the open form and to enable the clamping process is one of the key elements in the stent-design process. In the first part of the work, an original two-step procedure for stent-geometry design was proposed. This was due to the necessary selection of a geometry that would provide adequate support to the blood-vessel wall without causing damage to the vessel. Numerical simulations of the crimping and deployment processes were performed to verify the method. At the end of this stage, the optimal stent was selected for further testing. In addition, numerical simulations of selected experimental tests (catheter-crimping process, compression process) were used to verify the obtained geometrical forms. The results of experimental tests on stents produced by the microinjection method are presented. The digital image correlation (DIC) method was used to compare the results of numerical simulation and experimental tests. The two-step modeling approach was found to help select the appropriate geometry of the expanded stent, which is an extremely important step in the design of the crimping process. In the part of the paper where the results obtained by numerical simulation were compared with those gained by experiment and using the DIC method, a good compatibility of the displacement results can be observed. For both longitudinal and transverse (pinch) stent compression, the results practically coincide. The paper presents also the application of the DIC method which significantly expands the research possibilities, allowing for a detailed inspection of the deformation state and, above all, verification of local dangerous areas. This approach significantly increases the possibility of assessing the quality of the stents.

Temporal, biomechanical evaluation of a novel, transcatheter polymeric aortic valve in ovine aortic banding model.

Objectives: The aim of the study is to evaluate the functionality, durability, and temporal biocompatibility of a novel, balloon-expandable polymeric transcatheter heart valve (ATHV) system (InFlow, CardValve Consortium, Poland). Along with expanding TAVI indications, the demand for new transcatheter valves is increasing. Methods: A surgical ascending aortic banding model was created in 20 sheep. Two weeks later, 16 sheep were implanted with ATHV systems (15-16F). Three animals were euthanized after a 30-day follow-up, four animals after a 90-day follow-up, and six animals after a 180-day follow-up. A follow-up transthoracic echocardiography (TTE) was performed. Results: There was one procedure-related (6,25%) and two model-related deaths (12,5%; banding site calcification with subsequent infection originating externally from banding). TTE revealed the flow gradients (max/average) of 30,75/17,91; 32,57/19,21; and 21,34/10,63 mmHg at 30, 90, and 180 days, respectively. There were two cases of low-degree regurgitation after 180 days with no perivalvular leak observed. Histopathological analysis showed no valve degeneration at terminal follow-up with optimal healing. Small thrombi were present at the aortic wall adjacent to the base of the leaflets, and between the aortic wall and the stent in most of the valves; however, leaflets remained free from thrombi in all cases. Scanty calcifications of leaflets were reported in three animals evaluated 180 days after implantation. Conclusion: This preclinical study in the aortic banding model showed good hemodynamic performance, durability, and biocompatibility of the novel ATHV. Furthermore, regulatory studies with longer follow-ups are warranted.

Dual-jet electrospun PDLGA/PCU nonwovens and their mechanical and hydrolytic degradation properties.

A dual-jet electrospinning was used to mix a different hydrophilicity poly(carbonate urethanes) (PCUs) nanofibers with a biodegradable poly(D,L-lactide-co-glycolide) (PDLGA) copolyester microfibers. As a result, PDLGA/PCU partially degradable nonwovens consisting of an interlaced of both components fibers were obtained. In order to examine the hydrolytic degradation process of polyester fraction, as well as changes that occurred in the mechanical properties of the whole nonwovens, gel permeation chromatography, proton nuclear magnetic resonance spectroscopy, differential scanning calorimetry and scanning electron microscopy as well as static tensile test were performed. Obtained results showed that for the introduction of more hydrophobic PCU nanofibers (ChronoSil), the process of copolyester chain scission slowed down and the erosion mechanism proceeded in bulk. Unexpectedly, even greater deceleration of PDLGA fibers degradation was observed in case of more hydrophilic PCU (HydroThane), and erosion mechanism changed to surface. Enhancement the affinity of the whole nonwoven to the water, manifested by strong water uptake, facilitated the diffusion processes of both: water and acid degradation by-products, which limited autocatalysis reactions of the hydrolysis of ester bonds. On the other hand, strength tests showed the synergy in the mechanical characteristics of both components. Presented method allows influencing the mechanism and rate of polyester degradation without changing its chemical composition and physical properties, affecting only the physical interactions between the nonwoven and the degradation environment, and thus, on diffusion processes. Obtained partially degradable materials possessed also time prolonged functional properties, compared to the copolyester-only nonwoven itself, thus could be considered as promising for biomedical applications e.g. in drug release systems, implants or surgical meshes for supporting soft tissues.

Nonwoven Releasing Propolis as a Potential New Wound Healing Method-A Review.

Wound healing poses a serious therapeutic problem. Methods which accelerate tissue regeneration and minimize or eliminate complications are constantly being sought. This paper is aimed at evaluation of the potential use of biodegradable polymer nonwovens releasing propolis as wound healing dressings, based on the literature data. Propolis is honeybee product with antioxidant, antibacterial, antifungal, anticancer, anti-inflammatory, analgesic, and regenerative properties. Controlled release of this substance throughout the healing should promote healing process, reduce the risk of wound infection, and improve aesthetic effect. The use of biodegradable aliphatic polyesters and polyester carbonates as a propolis carrier eliminates the problem of local drug administration and dressing changes. Well-known degradation processes and kinetics of the active substance release allows the selection of the material composition appropriate to the therapy. The electrospinning method allows the production of nonwovens that protect the wound against mechanical damage. Moreover, this processing technique enables adjusting product properties by modifying the production parameters. It can be concluded that biodegradable polymer dressings, releasing a propolis, may find potential application in the treatment of complicated wounds, as they may increase the effectiveness of treatment, as well as improve the patient's life quality.

The Composites of PCL and Tetranuclear Titanium(IV)-oxo Complexes as Materials Exhibiting the Photocatalytic and the Antimicrobial Activity.

Excessive misuse of antibiotics and antimicrobials has led to a spread of microorganisms resistant to most currently used agents. The resulting global threats has driven the search for new materials with optimal antimicrobial activity and their application in various areas of our lives. In our research, we focused on the formation of composite materials produced by the dispersion of titanium(IV)-oxo complexes (TOCs) in poly(ε-caprolactone) (PCL) matrix, which exhibit optimal antimicrobial activity. TOCs, of the general formula [Ti4O2(OiBu)10(O2CR')2] (R' = PhNH2 (1), C13H9 (2)) were synthesized as a result of the direct reaction of titanium(IV) isobutoxide and 4-aminobenzoic acid or 9-fluorenecarboxylic acid. The microcrystalline powders of (1) and (2), whose structures were confirmed by infrared (IR) and Raman spectroscopy, were dispersed in PCL matrixes. In this way, the composites PCL + nTOCs (n = 5 and 20 wt.%) were produced. The structure and physicochemical properties were determined on the basis of Raman microscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), electron paramagnetic resonance spectroscopy (EPR), and UV-Vis diffuse reflectance spectroscopy (DRS). The degree of TOCs distribution in the polymer matrix was monitored by scanning electron microscopy (SEM). The addition of TOCs micro grains into the PCL matrix only slightly changed the thermal and mechanical properties of the composite compared to the pure PCL. Among the investigated PCL + TOCs systems, promising antibacterial properties were confirmed for samples of PCL + n(2) (n = 5, 20 wt.%) composites, which simultaneously revealed the best photocatalytic activity in the visible range.

Electrospun paclitaxel delivery system based on PGCL/PLGA in local therapy combined with brachytherapy.

The local administration of different drugs in anticancer therapy continue to attract attention. Thus, the idea of local delivery of cytostatics from nonwoven-structured polyesters seems to be highly desirable. It could reduce systemic drug levels and provide high local concentration of the chemotherapeutics at the tumor site and contribute to enhance the efficiency of the anticancer therapy. Poly(glycolide-ɛ-caprolactone) (PGCL) and poly(D,L-lactide-co-glycolide) (PLGA) synthesized with zirconium-based initiator have been used to prepare electrospun, drug-eluting patches since they possess very good fiber-forming ability. Well-known chemotherapeutic drug-paclitaxel has been loaded into fibrous structure as a model anticancer agent in order to obtain drug delivery systems for local administration. The drug dose in obtained nonwovens might be regulated by the thickness and total area of the implanted patches. Electrospinning of PGCL/PLGA blend allowed to obtain soft and flexible implantable materials. Flexibility has been important factor since it ensures convenient use when covering a tumor or filling a resection cavity. The effectiveness of designed nonwovens presented in the study has been tested in vivo on mouse model of breast cancer. The growth of the tumors was slowed down during in vivo study in comparison with drug-free nonwovens- The volume of the tumor was 40% lower. Drug-loaded electrospun systems implanted locally to the tumor site was further combined with brachytherapy which improved the effectiveness of the therapy in about 18%. Detailed analysis of the nonwovens before and during degradation process has been performed by means of Scanning Electron Microscopy, Differential Scanning Calorimetry, Nuclear Magnetic Resonance, Gel Permeation Chromatography, X-ray Diffraction. The molar mass changes of the nonwoven were quite rapid contrary to changes of comonomer unit content, thermal properties and morphology of the fiber.

Bioresorbable, electrospun nonwoven for delayed and prolonged release of temozolomide and nimorazole.

Glioblastoma multiforme is the most aggressive and lethal form of brain tumour due to the high degree of cancer cells infiltration into surrounding brain tissue. No form of monotherapy can guarantee satisfactory patient outcomes and is only of palliative importance. To find a potential option of glioblastoma treatment the bioresorbable, layer nonwoven mats for controlled temozolomide and nimorazole release were obtained by classical and coaxial electrospinning. Optimization of fibre structure that enables delayed and controlled drug release was performed. The studied bioresorbable polymers were poly(L-lactide-co-ε-caprolactone) and poly(L-lactide-co-glycolide-co-trimethylene carbonate). The physicochemical properties of polymers were determined as well as drug release profiles of nonwoven mats. A combination of coaxial electrospinning and electrospray technique provided three-phased release profiles of temozolomide and nimorazole: the slow release of very low drug doses followed by accelerated release and saturation phase. Results form the basis for further investigation since both studied polymers possess a great potential as nimorazole and temozolomide delivery systems in the form of layered nonwoven implants.

Biodegradable Electrospun Nonwovens Releasing Propolis as a Promising Dressing Material for Burn Wound Treatment.

The selection of dressing is crucial for the wound healing process. Traditional dressings protect against contamination and mechanical damage of an injured tissue. Alternatives for standard dressings are regenerating systems containing a polymer with an incorporated active compound. The aim of this research was to obtain a biodegradable wound dressing releasing propolis in a controlled manner throughout the healing process. Dressings were obtained by electrospinning a poly(lactide-co-glycolide) copolymer (PLGA) and propolis solution. The experiment consisted of in vitro drug release studies and in vivo macroscopic treatment evaluation. In in vitro studies released active compounds, the morphology of nonwovens, chemical composition changes of polymeric material during degradation process, weight loss and water absorption were determined. For in vivo research, four domestic pigs, were used. The 21-day experiment consisted of observation of healing third-degree burn wounds supplied with PLGA 85/15 nonwovens without active compound, with 5 wt % and 10 wt % of propolis, and wounds rinsed with NaCl. The in vitro experiment showed that controlling the molar ratio of lactidyl to glycolidyl units in the PLGA copolymer gives the opportunity to change the release profile of propolis from the nonwoven. The in vivo research showed that PLGA nonwovens with propolis may be a promising dressing material in the treatment of severe burn wounds.

The Estimation of Blood Paramagnetic Center Changes during Burns Management with Biodegradable Propolis-Nanofiber Dressing.

The evolution of the paramagnetic center system in blood during the healing of skin burn wounds dressed with a biodegradable apitherapeutic nanofiber dressing was examined. The aim of this study was to determine the changes in paramagnetic centers in blood during the influence of apitherapeutic nanofiber dressings on the healing process. The blood samples were tested before burn infliction (day 0) and, respectively, on the 10th and 21st days of the experiment. Paramagnetic centers in the blood of the pig used as the model animal were examined with an X-band (9.3 GHz) electron paramagnetic resonance spectroscopy. The EPR spectra were measured with Bruker spectrometer at 230 K with a modulation frequency of 100 kHz. The EPR lines of the high spin Fe3+ in methemoglobin, high spin Fe3+ in transferrin, Cu2+ in ceruloplasmin, and free radicals were observed in the multicomponent spectra of blood. For the application of the apitherapeutic nanofiber dressing, the amplitudes of the EPR signals of Fe3+ in methemoglobin were similar up to 10 days. For the experiment with the apitherapeutic formulation, the heights of EPR signals of Fe3+ in transferrin were lower after 10 days and 21 days of therapy, compared to day 0. For the application of the apitherapeutic formulation the signals of Cu2+ in ceruloplasmin and free radicals, strongly decreased after 10 days of therapy, and after 21 days it increased to the initial values characteristic for day 0. The apitherapeutic formulation caused that after 21 days the EPR spectrum of Cu2+ in ceruloplasmin and free radicals was considerably high. The apitherapeutic formulation interaction after 10 days and after 21 days of therapy resulted in the low EPR lines of Fe3+ in methemoglobin. EPR spectra of blood may be useful for presentation of the changes in its paramagnetic centers during the healing process of the burn wounds.

EPR Spectroscopic Examination of Different Types of Paramagnetic Centers in the Blood in the Course of Burn Healing.

The multicomponent electron paramagnetic resonance spectra of the blood during healing of skin burned wounds treated with a new generation biodegradable dressings containing poly(lactide-co-glycolide) were analysed. The evolution of different types of paramagnetic centers in the blood with time of healing was determined. The EPR spectra of the blood samples at 230 K temperature were measured at 1, 10, and 21 days after burning of the pig skin. The EPR lines of the following paramagnetic centers: the high-spin Fe3+ in methemoglobin (line I), high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) were observed in the X-band (9.3 GHz) spectra of the blood. The multicomponent structure of the EPR spectra of the tested blood samples depended on the time of the healing of the burned wounds. The amount of the high-spin Fe3+ in methemoglobin (line I) in the blood decreased after 21 days of the healing of the burned wounds. The amount of the high-spin Fe3+ in transferrin (line II) slightly increased after 21 days of therapy with the basis. The amount of Cu2+ in ceruloplasmin and free radicals (line III) in the blood was very high after 10 days of therapy. At the first day of the healing of the burned wounds, the highest amount of the high-spin Fe3+ in methemoglobin (line I), the relatively lower amounts of the high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) existed in the blood. In the medium phase (after 10 days) of the healing of the burned wounds, the extremely higher amounts of Cu2+ in ceruloplasmin and free radicals (line III) appeared in the blood. In the last phase (after 21 days), only the low differences between the amounts of the high-spin Fe3+ in methemoglobin (line I), the high-spin Fe3+ in transferrin (line II), and Cu2+ in ceruloplasmin and free radicals (line III) were observed. The present study may serve as a starting point for the development of a new technique for monitoring molecular complexes containing iron Fe3+ (methemoglobin, transferrin) or copper Cu2+ ions (ceruloplasmin) and free radicals in the blood during wound healing.