Real-time in vivo imaging of surface-modified liposomes to evaluate their behavior after pulmonary administration

Our previous study demonstrated that surface modification of liposomes using polyvinyl alcohol with a hydrophobic anchor (PVA-R) achieved sustained absorption from the lung after pulmonary administration and prolonged the pharmacological effects of the model peptide drug. In the present study, the behavior of PVA-R-modified liposomes in the lung and whole body was monitored using a real-time in vivo imaging system. Subsequently, the influence of surface modification with PVA-R on liposomal behavior in lung tissue was examined. Indocyanine green (ICG) was used as a near-infrared label of PVA-R-modified liposomes and was used to observe their dynamic behavior using non-invasive in vivo imaging (IVIS® imaging system) after pulmonary administration to rats. PVA-R-modified submicron-sized liposomes (ssLips) induced long-term retention in the lung compared with unmodified liposomes. Moreover, liposome association with alveolar macrophages (NR8383) was decreased by PVA-R modification in vitro. Therefore, PVA-R modification may prevent rapid elimination of ssLips by macrophages, thereby increasing retention in the lung.     

Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells

PurposeIn present investigation, recombinant human interferon-α-2b (rhINF-α-2b) loaded aquasomes were prepared, optimized and overlaid with PEGylated phospholipid to offer prolong release and high therapeutic index against ovarian cancer, SKOV3 cells.Methods and resultsCentral Composite Design (CCD) and Response Surface Methodology (RSM) were employed to calculate the optimized conditions, 1:3 core to coat ratio, sonication power of 12.5 W and time of about 55 min for preparation of aquasomes. Consequently, rhINF-α-2b-Py-5-P-Aq.somes exhibited higher protein loading capacity and retained structural conformations of rhINF-α-2b, as compared to rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄). Further, optimized rhINF-α-2b-Py-5-P-Aq.somes was superimposed with phospholipid-PEG₂₀₀₀ to prolong the release pattern of rhINF-α-2b from aquasomes. The rhINF-α-2b-core (CaHPO₄) released 97.3% of protein in 1 h, while 95.3% of rhINF-α-2b was released by rhINF-α-2b-Tre-Aq.somes in 4 h. Concurrently, rhINF-α-2b-Cellob-Aq.somes and rhINF-α-2b-Py-5-P-Aq.somes released 96.2% and 97.8% of rhINF-α-2b respectively in 6 and 8 h. Ultimately, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ displayed evidence of its prolonged release pattern and released 98.1% of rhINF-α-2b in 336 h. FT–IR and XRD substantiated the involvement of vigorous intermolecular hydrogen bonding and amorphous geometry in rhINF-α-2b-Py-5-P-Aq.somes. In last, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ exhibited the ∼ 4.55, 1.92, 2.3, 2.8, and 3.84 fold reductions in IC₅₀ as compared to free rhINF-α-2b, rhINF-α-2b-Py-5-P-Aq.somes, rhINF-α-2b-Cellob-Aq.somes, rhINF-α-2b-Tre-Aq.somes and rhINF-α-2b-Core (CaHPO₄), respectively.ConclusionTherefore, rhINF-α-2b-Py-5-P-Aq.somes-P-PEG₂₀₀₀ warrant further in depth in vitro and in vivo antitumor study to scale up the technology for clinical intervention.     

Surface studies of coated polymer microspheres and protein release from tissue-engineered scaffolds

The controlled release of growth factors from porous, polymer scaffolds is being studied for potential use as tissue-engineered scaffolds. Biodegradable polymer microspheres were coated with a biocompatible polymer membrane to permit the incorporation of the microspheres into tissueengineered scaffolds. Surface studies with poly(D,L-lactic-co-glycolic acid) [PLGA], and poly(vinyl alcohol) [PVA] were conducted. Polymer films were dip-coated onto glass slides and water contact angles were measured. The contact angles revealed an initially hydrophobic PLGA film, which became hydrophilic after PVA coating. After immersion in water, the PVA coating was removed and a hydrophobic PLGA film remained. Following optimization using these 2D contact angle studies, biodegradable PLGA microspheres were prepared, characterized, and coated with PVA. X-ray photoelectron spectroscopy was used to further characterize coated slides and microspheres. The release of the model protein bovine serum albumin from PVA-coated PLGA microspheres was studied over 8 days. The release of BSA from PVA-coated PLGA microspheres embedded in porous PLGA scaffolds over 24 days was also examined. Coating of the PLGA microspheres with PVA permitted their incorporation into tissue-engineered scaffolds and resulted in a controlled release of BSA.     

Structural and permeability characterization of biosynthetic PVA hydrogels designed for cell-based therapy

Incorporation of extracellular matrix (ECM) components to synthetic hydrogels has been shown to be the key for successful cell encapsulation devices, by providing a biofunctional microenvironment for the encapsulated cells. However, the influence of adding ECM components into synthetic hydrogels on the permeability as well as the physical and mechanical properties of the hydrogel has had little attention. Therefore, the aim of this study was to investigate the effect of incorporated ECM analogues on the permeability performance of permselective synthetic poly(vinyl alcohol) (PVA) hydrogels in addition to examining the physico-mechanical characteristics. PVA was functionalized with a systematically increased number of methacrylate functional groups per chain (FG/c) to tailor the permselectivity of UV photopolymerized hydrogel network. Heparin and gelatin were successfully incorporated into PVA network at low percentage (1%), and co-hydrogels were characterized for network properties and permeability to bovine serum albumin (BSA) and immunoglobulin G (IgG) proteins. Incorporation of these ECM analogues did not interfere with the base PVA network characteristics, as the controlled hydrogel mesh sizes, swelling and compressive modulii remained unchanged. While the permeation profiles of both BSA and IgG were not affected by the addition of heparin and gelatin as compared with pure PVA, increasing the FG/c from 7 to 20 significantly limited the diffusion of the larger IgG. Consequently, biosynthetic hydrogels composed of PVA with high FG/c and low percent ECM analogues show promise in their ability to be permselective for various biomedical applications.     

三氯羟苯醚/共聚体牙膏与非共聚体牙膏对牙菌斑、牙龈炎的临床效果

目的 :比较市售三氯羟苯醚 /共聚体牙膏与非共聚体牙膏对减少成年人牙菌斑、牙龈炎的效果。方法 :采用双盲、分层、平行的临床研究 ,对 183名健康成年人 (试验组 89人、对照组 94人 )进行了为期 6个月的临床效果评价。按同一标准 (Quigley HeinPlI ,Loe SilnessGI)于试验前、试验后 3月、6月分 3次对受试对象的菌斑与牙龈炎状况进行了检查。试验对象每日使用分配的牙膏和软毛牙刷早晚刷牙各 1次。结果 :三氯羟苯醚共聚体与非共聚体牙膏均能有效地抑制菌斑与牙龈炎。试验 3月、6月 ,菌斑指数试验组与对照组比较差异无显著。牙龈炎指数三氯羟苯醚 /共聚体牙膏与非共聚体牙膏比较分别降低 13 .46% (P >0 .0 5 ) ,2 5 .86% (P <0 .0 5 )。结论 :每天两次使用三氯羟苯醚 /共聚体牙膏与不含共聚体的牙膏都能显著减少牙菌斑、改善牙龈健康。而含三氯羟苯醚 /共聚体牙膏在改善牙龈健康方面更优于不含共聚体的牙膏。     

The Effect of Uterine Artery Embolization on Premenstrual Symptoms in Patients with Symptomatic Fibroids or Adenomyosis

PurposeTo evaluate whether uterine artery embolization (UAE) can reduce the premenstrual symptoms in women undergoing UAE for fibroid tumors or adenomyosis.Materials and MethodsAmong 141 women who underwent UAE for symptomatic fibroid tumors or adenomyosis at a single institution between March 2011 and February 2013, 54 premenstrual symptoms in 39 patients were prospectively analyzed. Premenstrual symptoms were rated by the patient on a scale of 0 to 10, with 0 representing no symptom and 10 representing the baseline severity. The change in premenstrual symptom score was calculated by subtracting the baseline score from the post-UAE score. At 3–6 months after UAE, each woman also completed a symptom severity questionnaire to assess the severity of menstrual bleeding to compare the changes in premenstrual symptoms scores between women with and without menorrhagia.ResultsBack pain, headache, and gastrointestinal symptoms (eg, constipation, indigestion, lower abdominal pain) were significantly improved after UAE (P < .05). Muscle pain, fatigue, nervousness, breast tenderness, and systemic edema were also improved, but not significantly so. The mean premenstrual symptom score change in patients with menorrhagia was significantly greater than in those without menorrhagia (−6.4 vs −3.7; P = .044).There was no correlation between the degree of menorrhagia score change and the degree of premenstrual symptom score change (P = .186).ConclusionsUAE could be a method to alleviate some premenstrual symptoms in patients with uterine fibroid tumors or adenomyosis.     

Embolization of symptomatic renal angiomyolipoma with a mixture of lipiodol and PVA,a mid-term result

Objective： To evaluate the clinical effect of renal artery embolization with a mixture of lipiodol and polyvinyl alcohol （PVA） particles on symptomatic renal angiomyolipoma and to present the mid-term results from our single-center site. Methods： We performed a retrospective review of the seven patients who underwent embolization with a mixture of lipiodol and PVA particles to treat symptomatic renal angiomyolipoma in our center between February 2011 and December 2013. Medical records and follow-up results were reviewed and analyzed. Results： Seven patients underwent eight episodes of embolization using a mixture of lipiodol and PVA particles to treat symptomatic renal angiomyolipoma. One patient required a subsequent embolization of the right kidney 9 months after the initial embolization of the left kidney. No nephrectomy was required in any of these cases during follow-up. None had recurrence of tumor bleeding or rupture during follow-up. Decreased tumor size was achieved in six patients （85.7%） during the mid-term follow-up. Conclusions： Embolization with a mixture of lipiodol and PVA particles is an effective and safe treatment for symptomatic renal angiomyolipoma. Based on the durable mid-term results of the present study, a mixture of lipiodol and PVA particles is recommended for embolization.     

The Role of Accessory Obturator Arteries in Prostatic Arterial Embolization

In 9 of 491 patients (1.8%) who underwent prostatic arterial embolization (PAE) for benign prostatic hyperplasia from March 2009–November 2013, prostatic arteries arose from the external iliac artery via an accessory obturator artery (AOA). Computed tomography angiography performed before the procedure identified the variant and allowed planning before the procedure. The nine AOAs were catheterized from a contralateral femoral approach. Bilateral PAE was technically successful in the nine patients. There was a mean decrease in international prostate symptom score of 6.5 points and a mean prostate volume reduction of 15.1% (mean follow-up, 4.8 mo) in the nine patients.     

平阳霉素用于婴幼儿地中海贫血部分性脾动脉栓塞术的疗效

目的：评价平阳霉素用于婴幼儿地中海贫血部分性脾动脉栓塞的疗效。方法：对临床确诊的婴幼儿地中海贫血24例,分两组,A组（12例）采用平阳霉素（PYM）＋明胶海绵颗粒作为栓塞剂,B组（12例）采用PVA颗粒作栓塞剂。结果：术后随访6个月,两组病例术后2周内红细胞计数及血红蛋白含量均较术前明显提高。半年后,A组红细胞计数及血红蛋白含量均保持在较高的水平,B组红细胞计数及血红蛋白含量下降趋势明显。结论：PYM＋明胶海绵颗粒作栓塞剂近中期疗效满意,远期疗效还需进_步观察。     

Study on a novel copper-containing composite for contraception

Background

The copper-containing intrauterine devices (Cu-IUDs) are being increasingly used worldwide as an effective contraception for family planning. To avoid abnormal bleeding, pain, partial and complete expulsion, which are associated with the burst release of cupric ions during the first few days, a novel cross-linked composite based on polyvinyl alcohol (PVA) that contained cupric ions, but not metallic copper, was developed by our research team.

Study Design

As a logical extension of our previous work, the corrosion products and release behavior of this composite after immersing in simulated body fluid (SBF) for 1 year were studied by X-ray fluorescence spectroscopy (XRF), X-ray diffraction (XRD) and atomic absorption spectrophotometry (AAS).

Results

No other new elements, such as P, Cl and Ca, appeared on the surface of the composite, and no Cu₂O was formed after immersing in SBF for 1 year, indicating that the effectiveness of copper can be greatly improved. Furthermore, no significant change on time dependence was found for the release rates of cupric ions in the composite compared with that of metallic copper, suggesting the absent burst release of cupric ions in the composite.

Conclusion

The present in vitro long-term data suggest that this novel copper-containing composite has potential as a substitute for conventional materials used in the manufacture of IUDs.