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.

Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells.

Co-delivery of epothilone B (EpoB) and rapamycin (Rap) increases cytotoxicity against various kinds of cancers. However, the current challenge is to develop a drug delivery system (DDS) for the simultaneous delivery and release of these two drugs. Additionally, it is important to understand the release mechanism, as well as the factors that affect drug release, in order to tailor this process. The aim of this study was to analyze PLA-PEG micelles along with several types of microspheres obtained from PLA or a mixture of PLA and PLA-PEG as carriers of EpoB and Rap for their drug release properties and cytotoxicity against breast cancer cells. The study showed that the release process of EpoB and Rap from a PLA-based injectable delivery systems depends on the type of DDS, morphology, and polymeric composition (PLA to PLA-PEG ratio). These factors also affect the biological activity of the DDS, because the cytotoxic effect of the drugs against MDA-MB-231 cells depends on the release rate. The release process from all kinds of DDS was well-characterized by the Peppas-Sahlin model and was mainly controlled by Fickian diffusion. The conducted analysis allowed also for the selection of PLA 50/PLA-PEG 50 microspheres and PLA-PEG micelles as a promising co-delivery system of EpoB and Rap.

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.

Bioresorbable copolymer of L-lactide and ε-caprolactone for controlled paclitaxel delivery.

Bioresorbable, aliphatic polyesters are known in medicine where serve as orthopedic devices (e.g., rods, pins and screws) or sutures and staples in wound closure. Moreover, such materials are extensively stud- ied as scaffolds--three-dimensional structures for tissue engineering but also drug delivery systems (DDS). The aim of this study was to determine the release profile of paclitaxel, one of the anti-inflammatory, antiprolifera- tive and anti-restenotic agent, from biocompatible copolymer of L-lactide and ε-caprolactone that seems to be very attractive especially for minimally invasive surgery due to its potential shape-memory property. The influ- ence of drug on copolymer hydrolytic degradation was also analyzed. Three types of matrices (3%, 5% of PTX and without drug) were prepared by solvent-casting method and degraded in vitro. The physicochemical changes of copolymer were analyzed by means of nuclear magnetic resonance spectroscopy (NMR), gel per- meation chromatography (GPC) and differential scanning calorimetry (DSC). The amount of drug released into media was monitored with the use of high-pressure liquid chromatography (HPLC). Similar drug release pro- files were obtained for matrices with paclitaxel. The drug-containing matrices degraded slightly slower than drug free matrices, regardless PTX content. Results of this work may be helpful in designing new bioresorbable paclitaxel delivery system applied in anti-cancer therapy or drug-eluting stents technology.