Polyvinylpyrrolidone-Coated Cubic Hollow Nanocages of PdPt3 and PdIr3 as Highly Efficient Self-Cascade Uricase/Peroxidase Mimics.

Uricase-catalyzed uric acid (UA) degradation has been applied for hyperuricemia therapy, but this medication is limited by H2O2 accumulation, which can cause oxidative stress of cells, resulting in many other health issues. Herein, we report a robust cubic hollow nanocage (HNC) system based on polyvinylpyrrolidone-coated PdPt3 and PdIr3 to serve as highly efficient self-cascade uricase/peroxidase mimics to achieve the desired dual catalysis for both UA degradation and H2O2 elimination. These HNCs have hollow cubic shape with average wall thickness of 1.5 nm, providing desired synergy to enhance catalyst's activity and stability. Density functional theory calculations suggest the PdIr3 HNC surface tend to promote OH*/O* desorption for better peroxidase-like catalysis, while the PdPt3 HNC surface accelerates the UA oxidation by facilitating O2-to-H2O2 conversion. The dual catalysis power demonstrated by these HNCs in cell studies suggests their great potential as a new type of nanozyme for treating hyperuricemia.

Curcumin-PVP improves the in vitro efficacy of ivermectin against resistant and susceptible Haemonchus contortus.

Ivermectin (IVM) resistance in parasitic nematodes such as Haemonchus contortus has spurred a search for substances that help to recover its efficacy. One potential agent is the natural product curcumin (CUR). In this study, CUR was combined with polyvinylpyrrolidone (PVP) (CUR/PVP) to improve its solubility and biological applicability. This study determined the effect of CUR preincubation on the effective concentration 50% (EC50) of IVM in three H. contortus isolates with different susceptibilities to IVM. The IVM EC50 was determined for three H. contortus isolates with different IVM susceptibilities using the larval migration inhibition (LMI) test. The three isolates were (i) PARAISO (IVM resistant), (ii) FMVZ-UADY (IVM susceptible), and (iii) CENID-SAI INIFAP (reference IVM susceptible). The L3 of each isolate were preincubated for 3 h with one of three concentrations of CUR (µg curcumin/mL): CONC-1 (3.67), CONC-2 (5.67), or CONC-3 (8.48). Corresponding controls were performed without CUR. The EC50 of IVM was determined for each isolate after they were exposed to the different CUR concentrations. The EC50 of IVM differed between the isolates PARAISO > FMVZ-UADY > CENID-SAI INIFAP (P < 0.05). The CUR preincubation at CONC-1 did not decrease the EC50 of IVM for any of the three isolates, suggesting a hormetic effect. By contrast, CUR preincubation at CONC-2 or CONC-3 decreased the IVM EC50 for the PARAISO isolate (P < 0.05) compared with the reference isolate and reduced the EC50 of IVM for the FMVZ-UADY and CENID-SAI INIFAP isolates below the EC50 for the CENID-SAI INIFAP isolate without CUR preincubation. In conclusion, preincubation of H. contortus L3 with CUR reduced the EC50 of IVM for field isolates classified as resistant and susceptible to IVM. The CUR preincubation reduced the IVM resistance factor in the different isolates tested.

AgNP-PVP-meglumine antimoniate nanocomposite reduces Leishmania amazonensis infection in macrophages.

BACKGROUND: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations. The adverse effects, immunosuppression and resistant strains associated with this disease necessitate the development of new drugs. Nanoparticles have shown potential as alternative antileishmanial drugs. We showed in a previous study the biosynthesis, characterization and ideal concentration of a nanocomposite that promoted leishmanicidal activity. In the present study, we conducted a specific analysis to show the mechanism of action of AgNP-PVP-MA (silver nanoparticle-polyvinylpyrrolidone-[meglumine antimoniate (Glucantime®)]) nanocomposite during Leishmania amazonensis infection in vitro. RESULTS: Through ultrastructural analysis, we observed significant alterations, such as the presence of small vesicles in the flagellar pocket and in the extracellular membrane, myelin-like structure formation in the Golgi complex and mitochondria, flagellum and plasma membrane rupture, and electrodense material deposition at the edges of the parasite nucleus in both evolutive forms. Furthermore, the Leishmania parasite infection index in macrophages decreased significantly after treatment, and nitric oxide and reactive oxygen species production levels were determined. Additionally, inflammatory, and pro-inflammatory cytokine and chemokine production levels were evaluated. The IL-4, TNF-α and MIP-1α levels increased significantly, while the IL-17 A level decreased significantly after treatment. CONCLUSIONS: Thus, we demonstrate in this study that the AgNP-PVP-MA nanocomposite has leishmanial potential, and the mechanism of action was demonstrated for the first time, showing that this bioproduct seems to be a potential alternative treatment for leishmaniasis.

Combining Mechanochemistry and Spray Congealing for New Praziquantel Pediatric Formulations in Schistosomiasis Treatment.

Praziquantel (PZQ) is the first line drug for the treatment of schistosome infections and is included in the WHO Model List of Essential Medicines for Children. In this study, the association of mechanochemical activation (MA) and the spray congealing (SC) technology was evaluated for developing a child-friendly PZQ dosage form, with better product handling and biopharmaceutical properties, compared to MA materials. A 1:1 by wt PZQ-Povidone coground-was prepared in a vibrational mill under cryogenic conditions, for favoring amorphization. PZQ was neat ground to obtain its polymorphic form (Form B), which has an improved solubility and bioactivity. Then, activated PZQ powders were loaded into microparticles (MPs) by the SC technology, using the self-emulsifying agent Gelucire® 50/13 as a carrier. Both, the activated powders and the corresponding loaded MPs were characterized for morphology, wettability, solubility, dissolution behavior, drug content, and drug solid state (Hot Stage Microscopy (HSM), Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction Studies (PXRD), and FT-IR). Samples were also in vitro tested for a comparison with PZQ against Schistosoma mansoni newly transformed schistosomula (NTS) and adults. MPs containing both MA systems showed a further increase of biopharmaceutical properties, compared to the milled powders, while maintaining PZQ bioactivity. MPs containing PZQ Form B represented the most promising product for designing a new PZQ formulation.

Dressings and topical agents for treating pressure ulcers.

BACKGROUND: Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and promote healing, and there are many options to choose from including alginate, hydrocolloid and protease-modulating dressings. Topical agents have also been used as alternatives to dressings in order to promote healing.A clear and current overview of all the evidence is required to facilitate decision-making regarding the use of dressings or topical agents for the treatment of pressure ulcers. Such a review would ideally help people with pressure ulcers and health professionals assess the best treatment options. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents. OBJECTIVES: To assess the effects of dressings and topical agents for healing pressure ulcers in any care setting. We aimed to examine this evidence base as a whole, determining probabilities that each treatment is the best, with full assessment of uncertainty and evidence quality. SEARCH METHODS: In July 2016 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: Published or unpublished randomised controlled trials (RCTs) comparing the effects of at least one of the following interventions with any other intervention in the treatment of pressure ulcers (Stage 2 or above): any dressing, or any topical agent applied directly to an open pressure ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factor treatments, platelet gels and larval therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessment and data extraction. We conducted network meta-analysis using frequentist mega-regression methods for the efficacy outcome, probability of complete healing. We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (saline gauze). We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals for individual treatments compared with every other, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole. MAIN RESULTS: We included 51 studies (2947 participants) in this review and carried out NMA in a network of linked interventions for the sole outcome of probability of complete healing. The network included 21 different interventions (13 dressings, 6 topical agents and 2 supplementary linking interventions) and was informed by 39 studies in 2127 participants, of whom 783 had completely healed wounds.We judged the network to be sparse: overall, there were relatively few participants, with few events, both for the number of interventions and the number of mixed treatment contrasts; most studies were small or very small. The consequence of this sparseness is high imprecision in the evidence, and this, coupled with the (mainly) high risk of bias in the studies informing the network, means that we judged the vast majority of the evidence to be of low or very low certainty. We have no confidence in the findings regarding the rank order of interventions in this review (very low-certainty evidence), but we report here a summary of results for some comparisons of interventions compared with saline gauze. We present here only the findings from evidence which we did not consider to be very low certainty, but these reported results should still be interpreted in the context of the very low certainty of the network as a whole.It is not clear whether regimens involving protease-modulating dressings increase the probability of pressure ulcer healing compared with saline gauze (risk ratio (RR) 1.65, 95% confidence interval (CI) 0.92 to 2.94) (moderate-certainty evidence: low risk of bias, downgraded for imprecision). This risk ratio of 1.65 corresponds to an absolute difference of 102 more people healed with protease modulating dressings per 1000 people treated than with saline gauze alone (95% CI 13 fewer to 302 more). It is unclear whether the following interventions increase the probability of healing compared with saline gauze (low-certainty evidence): collagenase ointment (RR 2.12, 95% CI 1.06 to 4.22); foam dressings (RR 1.52, 95% CI 1.03 to 2.26); basic wound contact dressings (RR 1.30, 95% CI 0.65 to 2.58) and polyvinylpyrrolidone plus zinc oxide (RR 1.31, 95% CI 0.37 to 4.62); the latter two interventions both had confidence intervals consistent with both a clinically important benefit and a clinically important harm, and the former two interventions each had high risk of bias as well as imprecision. AUTHORS' CONCLUSIONS: A network meta-analysis (NMA) of data from 39 studies (evaluating 21 dressings and topical agents for pressure ulcers) is sparse and the evidence is of low or very low certainty (due mainly to risk of bias and imprecision). Consequently we are unable to determine which dressings or topical agents are the most likely to heal pressure ulcers, and it is generally unclear whether the treatments examined are more effective than saline gauze.More research is needed to determine whether particular dressings or topical agents improve the probability of healing of pressure ulcers. The NMA is uninformative regarding which interventions might best be included in a large trial, and it may be that research is directed towards prevention, leaving clinicians to decide which treatment to use on the basis of wound symptoms, clinical experience, patient preference and cost.

Management of Mucositis During Chemotherapy: From Pathophysiology to Pragmatic Therapeutics.

Chemotherapy-induced mucositis is a common condition caused by the breakdown of the mucosal barrier. Symptoms can include pain, vomiting and diarrhoea, which can often necessitate chemotherapy treatment breaks or dose reductions, thus compromising survival outcomes. Despite the significant impact of mucositis, there are currently limited clinically effective pharmacological therapies for the pathology. New emerging areas of research have been proposed to play key roles in the development of mucositis, providing rationale for potential new therapeutics for the prevention, treatment or management of chemotherapy-induced mucositis. This review aims to address these new areas of research and to comment on the therapeutics arising from them.

Outcomes for split-thickness skin transplantation in high-risk patients using octenidine.

Skin transplantation is a commonly used surgical technique; however, the complication rate, including postoperative infection and delayed wound healing due to inefficient perfusion, is significantly higher in patients suffering from comorbidities. Hence, a subsequent repeat procedure is often necessary. In this report, two case studies are presented in which an octenidine-based antiseptic is used with a tie-over dressing (TOD) instead of povidone iodine (PVP-iodine), following a split-thickness skin graft. The two patients selected were deemed to be at high risk of impaired wound healing due to comorbidities. The first patient, a confirmed smoker with diabetes, presented with a nodular melanoma that was resected and covered with a split-thickness skin graft. After 5 days of negative pressure wound therapy as a TOD, in combination with PVP-iodine, the graft became necrotic. A second split-thickness skin graft was performed and an antiseptic regimen with octenidine in combination with the same TOD resulted in a completely healed transplant. The second patient, also a confirmed smoker with diabetes and receiving oral corticosteroid treatment, was diagnosed with a skin necrosis on her leg. Following the split-thickness skin graft, octenidine and TOD were applied. The patient's skin graft completely healed without any adverse events. These two case studies indicate that the combination of octenidine and TOD following split-thickness skin transplantation is safe, well-tolerated and appears to have positive benefits in the reconstruction of defects in patients with impaired wound healing.

[The role of surrogate alcoholic beverages in the development of hemorrhage in the patients presenting with Mallory-Weiss syndrome].

The objective of the present work was to study the pathological changes in various organs and tanatogenesis associated with Mallory-Weiss syndrome making use of the forensic medical and clinical materials. It was shown that the main cause of unrestrained vomiting resulting from alcoholic intoxication and leading to perfusive bleeding is not only the direct action of ethanol and surrogate alcohol on gastroesophageal mucosa and induced thrombocytopenia. Another cause may be brain oedema with subsequent cerebral herniation and irritation of the pseudobulbar centres responsible for the initiation of the vomiting reflex. The authors propose recommendations for forensic medical diagnostics of the cases of such hemorrhage.

[Assessing the effectiveness of Gelclair® in the prevention and therapy of stomatitis in patients undergoing hematopoietic stem-cell transplantation: a randomized trial]. / Valutazione dell'efficacia del Gelclair® nella prevenzione e cura della stomatite nei pazienti sottoposti a trapianto di cellule staminali emopoietiche: Studio randomizzato.

INTRODUCTION: Chemotherapy-induced stomatitis is a major side effect of the treatment. Numerous approaches are described in the literature for the prevention and treatment of this complication. OBJECTIVE: the aim was assess the effectiveness of Gelclair® in patients undergoing hematopoietic stem-cell transplantation in terms of reducing the incidence of stomatitis, stomatitis-pain and the severity of stomatitis INTERVENTIONS/METHODS: Fifty-seven patients (28 control group and 29 experimental group) used a mouthwash 3 times a day and were evaluated by means of a specially-tailored form containing the following assessment items:stomatitis evaluation scale (WHO), VAS for pain and Likert-Scale for agreement. RESULTS: 61% of patients presented with stomatitis. No difference was observed between the two groups with regard to stomatitis grade throughout the observation period. Painful symptoms were observed in 54% subjects. No differences were observed in terms of average pain perception before the use of mouthwashes throughout the period of observation p=0.06. RESULTS showed a pain-relieving effect in the experimental group after using the mouthwash p=0.04. CONCLUSIONS: Although Gelclair® had no influence on the onset and severity of stomatitis in transplanted patients, a significant benefit was observed in terms of pain control. Our study suggest the possibility to implementation the use of Gelclair® in clinical practice. However, further multicenter trials are needed to provide stronger evidence on the real usefulness of this product.

Efficacy of mouth rinses and toothpaste on tooth whitening.

OBJECTIVES: People increasingly desire tooth whitening. Considering the wide range of whitening products on the market, this study evaluated the efficacy of whitening toothpastes and mouth rinses compared with the 10% carbamide peroxide (CP) whitening gel. METHODS: We obtained 120 cylindrical specimens from bovine teeth, which were darkened for 24 hours in a coffee solution. The color measurement was performed by a spectrophotometer using the CIE L*a*b* system, and specimens were divided into six groups according to the use of the following agents: group 1, conventional fluoridated toothpaste; group 2, Close Up White Now; group 3, Listerine Whitening; group 4, Colgate Plax Whitening; group 5, experimental mouth rinse with Plasdone; and group 6, 10% CP Whiteness Perfect. After the simulation of 12 weeks of treatment for groups 1 to 5 and 14 days of treatment for group 6, the specimens were subjected to a new color reading. RESULTS: Data were subjected to one-way analysis of variance (α=0.05), which showed significant differences among groups after 12 weeks for ΔE (p=0.001). Results of the Tukey test revealed that groups 3, 4, and 6 presented significantly higher color alteration than groups 1, 2, and 5. CONCLUSIONS: The whitening toothpaste Close Up White Now and the experimental mouth rinse with Plasdone showed similar color alteration as conventional toothpaste after a 12-week treatment simulation. These groups presented significantly lower color alteration compared with whitening mouth rinses Listerine and Colgate Plax Whitening, which showed similar results to those observed after 14 days of bleaching with 10% CP treatment.

[The application of biopolymer-based antiseptic drugs for the surgical treatment of intranasal and paranasal tumours].

The authors report their experience with the application of the local antiseptic preparation Ambipor for the treatment of operative wound infection in the patients presenting with malignant neoplasms. Ambipor was used in 23 patients receiving surgical treatment of locally advanced intranasal and paranasal tumours. It was shown that the application of ambipor allows decreasing the risk of development of wound infection in the postoperative period.

The effect of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) on oral microbial colonization and pain control compared with other rinsing solutions in patients with oral mucositis after allogeneic stem cells transplantation.

BACKGROUND: Gelclair is an oral lubricating gel used in the management of oral mucositis (OM). We evaluated its efficacy, tolerance and impact on oral cavity microbial colonization in patients with OM after allogeneic hematopoietic stem cells transplantation. MATERIAL/METHOD: Gelclair was administered in a group of 22 patients with active OM. A control group of 15 patients used other rinsing solutions (chlorhexidine, benzydamine, salvia). Tests with oral cavity swabs for microbiology analysis were performed once a week. RESULTS: The characteristics of OM in both groups were comparable, and rinsing solutions had satisfactory tolerability. There was no difference in the median improvement of oral intake and OM-related pain relief, which was assessed mostly as "slight effect". In the Gelclair group, the effect duration was longer (median 3 [0-5] vs. 1 [0-3] hours, p = 0.001). There was significant increase of Enterococcus faecalis and Candida sp. colonization of the oral cavity over the course of the hospitalization and significantly reduced incidence of such colonization in patients with OM in the Gelclair group: 1/22 (5%) vs. 6/15 (40%), p = 0.01. In vitro tests showed inhibited growth of Enterococcus faecalis and Candida sp. colonies within the area of the Gelclair application. CONCLUSIONS: Gelclair may be individually helpful in the management of OM and pain in patients after allogeneic stem cells transplantation. Its use did not lead to worsened oral bacterial and yeast colonization and probably even helped to protect mucosa from Enterococcus and Candida sp. Further studies based on larger cohorts are needed.

A Patient With Bilateral Conjunctivitis Positive for SARS-CoV-2 RNA in a Conjunctival Sample.

PURPOSE: To present a patient with bilateral conjunctivitis, testing positive for viral RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both nasopharyngeal and conjunctival samples. METHODS: A 40-year-old man with bilateral acute conjunctivitis and suspicious signs of coronavirus disease 2019 (COVID-19) presented to the hospital. A detailed ophthalmic examination was performed. Samples obtained from conjunctival and nasopharyngeal swabs were tested by reverse transcription PCR (RT-PCR) for the detection of SARS-CoV-2 virus. Ocular findings and duration of the presence of viral RNA in the conjunctival specimens were evaluated at follow-up visits. RESULTS: Slit-lamp biomicroscopy revealed bilateral acute follicular conjunctivitis. The RT-PCR assay demonstrated the presence of viral RNA in the nasopharyngeal and conjunctival specimens at the initial visit and at the 4-day follow-up. Conjunctivitis findings were decreased after 4 days and recovered completely without any sequelae within10 days. The PCR results of both nasopharyngeal and conjunctiva specimens were negative for the viral RNA at 10 days. CONCLUSIONS: Bilateral conjunctivitis is rare in patients infected with COVID-19. Although it is difficult to detect viral RNA from conjunctival swabs, conjunctival secretions may be a source of contamination, and protective measures must be taken.

Prussian blue nanozyme-mediated nanoscavenger ameliorates acute pancreatitis via inhibiting TLRs/NF-κB signaling pathway.

Rationale: Acute pancreatitis (AP) is a serious acute condition affecting the abdomen and shows high morbidity and mortality rates. Its global incidence has increased in recent years. Inflammation and oxidative stress are potential therapeutic targets for AP. This study was conducted to investigate the intrinsic anti-oxidative and anti-inflammatory effects of Prussian blue nanozyme (PBzyme) on AP, along with its underlying mechanism. Methods: Prussian blue nanozymes were prepared by polyvinylpyrrolidone modification method. The effect of PBzyme on inhibiting inflammation and scavenging reactive oxygen species was verified at the cellular level. The efficacy and mechanism of PBzyme for prophylactically treating AP were evaluated using the following methods: serum testing in vivo, histological scoring following hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence staining, polymerase chain reaction array, Kyoto Encyclopedia of Genes and Genomes analysis and Western blotting analysis. Results: The synthetic PBzyme showed potent anti-oxidative and anti-inflammatory effects in reducing oxidative stress and alleviating inflammation both in vitro and in vivo in the prophylactic treatment of AP. The prophylactic therapeutic efficacy of PBzyme on AP may involve inhibition of the toll-like receptor/nuclear factor-κB signaling pathway and reactive oxygen species scavenging. Conclusion: The single-component, gram-level mass production, stable intrinsic biological activity, biosafety, and good therapeutic efficacy suggest the potential of PBzyme in the preventive treatment of AP. This study provides a foundation for the clinical application of PBzyme.

Corneal endothelium damage with intraocular lenses: contact adhesion between surgical materials and tissue.

Intraocular lenses destroy corneal endothelial cells by contact adhesion between the acrylic lens and endothelial surfaces during cataract surgery. Glass and rubber surgical glove surfaces produce similar cell damage. This phenomenon may be important in many surgical procedures and appears to be preventable if a hydrophilic polymer interface is interposed between contacting tissue and the surfaces of materials used.

[Role of polyvidone-iodine ablation in the management of symptomatic renal cysts]. / Place de la ponction-sclérothérapie à la polyvidone-iodine dans le traitement des kystes rénaux simples symptomatiques.

OBJECTIVE: To assess prospectively the results of percutaneous sclerotherapy with povidone-iodine of symptomatic renal cysts in adults. METHODS: Fifty two patients were included in this study from august 2004 to november 2006. The operative indication was: pain (41 cases), urinary tract compression (8 cases), and very large cyst (3 cases). The preoperative assessment (site and dimensions of the cyst) always included ultrasonography. CT scan, for morphological assessment, was performed in 39 cases. RESULTS: The mean age of patients was 63 years (47-75 years). The mean diameter was 76 mm. The cysts were punctured in all the cases directly under local anaesthesia and guided by sonography. The procedure was very well tolerated in every case, with external drainage for 72 hours. Clinical regression was complete in 48 cases (92%), with total ultrasonographic disappearing of the cysts in 31 cases (60%) with a mean follow-up of 14 months (3-29 months). CONCLUSION: Percutaneous sclerotherapy with povidone-iodine is a safe, effective and reproducible treatment of symptomatic renal cysts in adults.

Comparative study of riboflavin-UVA cross-linking and "flash-linking" using surface wave elastometry.

PURPOSE: To investigate comparative stiffness values in porcine corneas after standard cross-linking and a new, rapid method of cross-linking (flash-linking) using surface wave elastometry. METHODS: Ten porcine eyes were treated using an ultraviolet A (UVA) double diode light source with a wavelength of 370 nm and delivering an irradiance of 4.2 mW/cm2 at a distance of 1.2 cm while applying 0.1% riboflavin-5-phosphate drops to the central cornea every 5 minutes as a photosensitizer for 30 minutes (riboflavin-UVA group). The next 10 porcine corneas were treated with a single application of a customized photoactive crosslinking agent and 30 seconds of UVA light at the same power and wavelength (flash-linking group). Following treatment, the Sonic Eye system (PriaVision Inc) was used to measure ultrasound surface wave propagation time between two fixed-distance transducers applied to the cornea along central horizontal and vertical positions. Intraocular pressure was continuously monitored. RESULTS: Mean surface wave velocity was determined from the last 5 of 10 sequential measurements for each eye, and was 90.87 +/- 15.26 m/s for all eyes with a mean standard deviation (SD) of 2.34 m/s among each eye in the riboflavin-UVA group versus 83.66 +/- 12.30 m/s with a mean SD of 2.69 m/s among each eye in the flash-linking group before treatment and 109.2 +/- 21.76 m/s with a mean SD of 2.15 m/s among each eye (riboflavin-UVA group) versus 109.2 +/- 18.42 m/s with a mean SD of 2.26 m/s among each eye (flash-linking group) after cross-linking. The mean surface wave velocity increased by 18.3 units from 90.87 to 109.2 m/s (P = .003) after cross-linking with riboflavin-UVA, and by 25.5 m/s from 83.66 to 109.2 m/s (P = .0001) after flash-linking. Surface wave velocity was noted to increase after both cross-linking techniques, but the differences observed did not reach statistical significance (P = .74). CONCLUSIONS: A new, rapid method of cross-linking (flash-linking) is introduced by the use of a customized photoactive cross-linking agent. The method demonstrates similar efficacy in stiffening the cornea (when measured with surface wave elastometry) in comparison to standard cross-linking, but requires only 30 seconds of UVA exposure.

Toward understanding the high PDT efficacy of chlorin e6-polyvinylpyrrolidone formulations: photophysical and molecular aspects of photosensitizer-polymer interaction in vitro.

It is recognized that chlorin e6-polyvinylpyrrolidone (Ce6-PVP) formulations are characterized by a high efficacy in photodynamic therapy of malignant tumors. Currently, a commercially available formulation of this type is Photolon (Fotolon) with Ce6:PVP=1:1 (w/w) and the weight-average molecular weight of PVP is 1.2x10(4). To gain a better understanding of the role played by PVP in Ce6-PVP formulations, we carry out experiments on IR and UV-VIS absorption, steady-state and time-resolved fluorescence, time-resolved triplet-triplet absorption, octanol-water partitioning, and solubility of chlorin e6 in buffer solutions at pH 6.3, 7.4, and 8.5 in presence of PVP with Ce6:PVP ratios ranging from 1:0 to 1:1000 (w/w) for PVP samples with weight-average molecular weights of 8x10(3), 1.2x10(4), and 4.2x10(4). We show that Ce6 interacts with PVP by forming molecular complexes via hydrophobic interactions and determine the Ce6-PVP binding constant, as well as the mean number of PVP monomers per binding site. We find that complexation of Ce6 with PVP prevents Ce6 aggregation in aqueous media and leads to an enhancement of Ce6 fluorescence quantum yield, while keeping the quantum yield of the intersystem crossing essentially unchanged. Possible scenarios of how the presence of PVP can favorably affect the PDT efficacy of chlorin e6 in Ce6-PVP formulations are discussed.

Polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair): a bioadherent oral gel for the treatment of oral mucositis and other painful oral lesions.

BACKGROUND: Painful oral lesions in patients with cancer, HIV or aphthous ulcers can cause significant pain and discomfort. Those with oral mucositis (OM) resulting from high-dose chemotherapy or irradiation are the most at risk for painful lesions that lead to significant morbidity and mortality, decreased quality of life and increased economic costs. Numerous approaches have been taken to prevent and treat OM in the cancer patient but this condition remains a significant obstacle to cancer therapy. Small studies have been done in healing oral lesions arising from laser surgery and in wound healing but research is needed to support the use of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) in these clinical setting. OBJECTIVE: The purpose of this paper is to review the benefit of polyvinylpyrrolidone-sodium hyaluronate gel, a topical oral mucosal barrier gel to prevent or diminish the pain of OM and other oral lesions. METHODS: Primary resources in peer-reviewed journals, chapters in recognized textbooks and information from international and national oncology and dental medicine scientific meetings. CONCLUSIONS: Oncology patients receiving high-dose immunosuppressive therapy are the most at risk with painful OM. Current prevention and treatment options for OM have limited effectiveness. Although opioids are available for pain management, novel agents, to be used alone or in combination with other proven measures to decrease the severity and duration of OM, are emerging. Clinical studies in the use of polyvinylpyrrolidone-sodium hyaluronate to reduce the pain or disruption to the oral mucosa has merit. Few clinical trials or main publications have supported the use of this product. Robust randomized trials are needed to further support the clinical utility of this agent.

Microspherical Particles of Solid Dispersion of Polyvinylpyrrolidone K29-32 for Inhalation Administration.

Inhalation administration is a promising alternative to the invasive drug delivery methods. The particle size required for ideal drug aerosol preparation is between 1 and 3 µm. The application of microspherical particles of solid dispersions enhances bioavailability of poorly soluble drugs due to the solubilization. In the present work, the spray drying process of the production of microspherical particles of solid dispersions of polyvinylpyrrolidone K29-32 with model hydrophobic drug, phenacetin, was optimized using the results of DSC, PXRD, and viscometry. The diameter of the obtained particles is within 1-3 µm range. The Gibbs energy of dissolution in water was shown to be negative for the mixture with polymer/phenacetin mass ratio 5 : 1. We have demonstrated that the optimal size distribution for the inhalation administration is obtained for microspherical particles produced using spray caps with 7.0 µm hole size. The dissolution rates of phenacetin from the produced microspherical particles were faster than that of drug powder. As evidenced by powder X-ray diffraction data, phenacetin stayed in amorphous state for 4 months in microspherical particles of solid dispersions. According to the obtained results, strategic application of the spray drying process could be beneficial for the improvement of the pharmaceutical properties of model drug, phenacetin.