Vaginal Delivery of Paclitaxel via Nanoparticles with Non-Mucoadhesive Surfaces Suppresses Cervical Tumor Growth

Local delivery of chemotherapeutics in the cervicovaginal tract using nanoparticles may reduce adverse side effects associated with systemic chemotherapy, while improving outcomes for early stage cervical cancer. We hypothesize drug-loaded nanoparticles must rapidly penetrate cervicovaginal mucus (CVM) lining the female reproductive tract to effectively deliver their payload to underlying diseased tissues in a uniform and sustained manner. We develop paclitaxel-loaded nanoparticles, composed entirely of polymers used in FDA-approved products, which rapidly penetrate human CVM and provide sustained drug release with minimal burst effect. We further employ a mouse model with aggressive cervical tumors established in the cervicovaginal tract to compare paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (conventional particles , or CP) and similar particles coated with Pluronic® F127 (mucus-penetrating particles , or MPP). CP are mucoadhesive and, thus, aggregated in mucus, while MPP achieve more uniform distribution and close proximity to cervical tumors. Paclitaxel-MPP suppress tumor growth more effectively and prolong median survival of mice compared to free paclitaxel or paclitaxel-CP. Histopathological studies demonstrate minimal toxicity to the cervicovaginal epithelia, suggesting paclitaxel-MPP may be safe for intravaginal use. These results demonstrate for the first time the in vivo advantages of polymer-based MPP for treatment of tumors localized to a mucosal surface

Isıya hassas biyobozunan mPEG-PLLA blok kopolimerleri : sentez, karakterizasyon ve ilaç salım sistemlerinde uygulamaları; yeni elektrokromik poli (tiyonil pirol) sentezi ve özellikleri.

Syntheses of biodegradable PLLA homopolymers and PLLA-mPEG diblock copolymers for the formation of thermo-sensitive gels were performed. The sol-gel transition temperature of the matrix was adjusted by altering the length of each PEG and LA component. PLLA-mPEG biocompatible copolymers, having appropriate length of each block component, showed sols at around 42-45 oC, suitable for the injection, then a gel with subsequent rapid cooling to body temperature. Topotecan and camptothecin were selected as anti-cancer drugs. Both drugs can easily hydrolyze at physiological conditions (pH=7.4). This causes the loss of its activity, and it turns into inactive toxic carboxylate form from active lactone state. To keep those anti cancer drugs in the lactone form, they were efficiently loaded into PLLA-mPEG gels in different loading ratios. Their stability in gel was fully examined with HPLC and fluorescence spectroscopy. It was found that both drugs were highly stable and in active form in the prepared gels (>95 %). Then, both release profile of drugs at different loading ratios showed prolonged release over weeks. Mechanistic studies on the stabilization of CPT anti cancer drug with PLLA-mPEG gels were carried out using ATR-FTIR, confocal and optic microscopes. The cytotoxic efficacy of TPT in the PLLA-mPEG platform (PLLA-mPEG-TPT) was evaluated on LLC-1 and 4T1 cancer cell lines by MTT assay. In vivo, the administration of PLLA-mPEG-TPT to the mice bearing breast tumours established with 4T1 cells resulted in a significant reduction in tumour size and better survival percentages. Additionally, stabilization of CPT and TPT with gels may find another application on solid tumors in brain via local injection. A novel conducting polymer was successfully synthesized via electropolymerization of 1-(1H-pyrrol-1-yl)-2,5-di(thiophen-2-yl)-1H-pyrrole. The electrochemical and electro-optical properties of the corresponding polymer, which was the first example of polymer containing 1,1’-bipyrrole units, were elaborated using electroanalytical and spectroscopic techniques. Cyclic voltammograms and electrooptical studies showed that the polymer has a stable and well-defined reversible redox process as well as electrochromic behavior. The processable polymer film also possessed a yellowish orange light emitter property.Ph.D. - Doctoral Progra

A novel electrochromic and fluorescent polythienylpyrrole bearing 1,1 '-bipyrrole

A novel conducting polymer was successfully synthesized via electropolymerization of 1-(1H-pyrrol-1-yl)-2,5-di(thiophen-2-yl)-1H-pyrrole. The electrochemical and electro-optical properties of the corresponding polymer, which was the first example of polymer containing 1,1'-bipyrrole units, were elaborated using electroanalytical and spectroscopic techniques. Cyclic voltammograms and electro-optical studies showed that the polymer has a stable and well-defined reversible redox process as well as electrochromic behavior. The processable polymer film also possessed a yellowish orange light emitter property

Diagnostic value of elastography in the diagnosis of ıntermetatarsal neuroma

WOS: 000378071300006PubMed ID: 26964696The objective of the present study was to characterize the ultrasound and elastographic properties of intermetatarsal neuroma (interdigital neuroma) and their contribution to diagnosis. Eighteen patients with metatarsalgia, who had presented to an orthopedic clinic from April 2013 to February 2015, were diagnosed with 25 intermetatarsal neuromas (11 unilateral [61.11%], 7 bilateral [38.89%]). These patients underwent evaluation with ultrasonography and simultaneous ultrasound strain elastography to assess the elastographic properties of the tissues in the intermetatarsal space. The intermetatarsal neuroma diagnosis was confirmed by histopathologic inspection. The lesion contours, localization, dimensions, and vascularization were evaluated before surgical excision. The elasticity and strain ratio values were compared between the neuroma and adjacent healthy intermetatarsal space. Of the 25 intermetatarsal neuromas, 1 (4%) was not detected by ultrasonography (incidence of detection of 96%). The mean neuroma width was 6.35 (range 3.7 to 13) mm in the coronal plane, and the mean elasticity and strain ratio values were 3.44 (range 1.1 to 5.1) and 9.47 (range 2.3 to 19.3), respectively. The elasticity and strain ratio values were significantly greater in the presence of an interdigital neuroma than in the adjacent healthy intermetatarsal spaces (Z = - 3.964, p = .0001 and Z = -3.927, p = .0001, respectively). The diagnostic cutoff values were calculated as 2.52 for elasticity and 6.1 for the strain ratio. Four neuromas (16%) were not demarcated, and the elasticity and strain ratio values for these were lower than those for neuromas with demarcated contours but were greater than those for healthy intermetatarsal spaces (p < .006 and p < .005, respectively). Patients with clinically suspected intermetatarsal neuromas that do not show demarcation and with smaller lesions might benefit from the use of ultrasound elastography for diagnosis

Novel and eco-friendly hydrophobic treatment of cotton and polyester fabrics based-on octavinyl and aminopropylisobutyl polyhedral oligomeric silsesquioxanes (OL-POSS and AM-POSS)

The hydrophobicity of cotton and polyester fabrics plays a significant role in various industrial applications. Anchoring hydrophobic chemicals onto the fabric surface is one of the major strategies. Fluorinated chemicals are widely employed to construct hydrophobic surfaces. However, alternative hydrophobic coatings are urgently sought by researchers due to the potential risks and hazards of fluorinated chemicals. Polyhedral oligomeric silsesquioxanes (POSS) are one of the most potential alternatives as they increase the roughness and lower the surface energy through chemical enhancement of the surface. In this work, hydrophobic cotton and polyester surfaces were fabricated anchoring Octavinyl POSS (OL-POSS) and Aminopropylisobutyl POSS (AM-POSS) onto the surface via one-step dip-coating technique. To enhance the surface roughness and the hydrophobicity, Ultraviolet (UV) radiation was employed with Benzoyl Peroxide (BPO) initiator. Water contact angle (WCA) of both fabrics increased from 0° to 136° using 5% POSS coatings with initiator and UV present. Water absorption duration (WAD) also increased from several seconds up to 310 min. Furthermore, 5% POSS modified fabrics gave similar or better WAD values when compared to coatings treated with fluorinated chemicals. The findings confirmed that OL-POSS and AM-POSS coatings are eligible environmentally friendly candidates for the replacement of fluorinated chemicals