The use of methylene blue to control the tumor oxygenation level.

BACKGROUND: Hypoxia is a characteristic feature of many tumors. It promotes tumor proliferation, metastasis, and invasion and can reduce the effectiveness of many types of cancer treatment. OBJECTIVE: The aim of this study was to investigate the pharmacokinetics of methylene blue (MB) and its impact on the tumor oxygenation level at mouse Lewis lung carcinoma (LLC) model using spectroscopic methods. APPROACH: The pharmacokinetics of MB were studied qualitatively and quantitatively using video fluorescence imaging and fluorescence spectroscopy. The degree of hemoglobin oxygenation in vivo was examined by calculating hemoglobin optical absorption from the measured diffuse reflectance spectra. The distribution of MB fluorescence and the lifetime of NADH were analyzed using laser scanning microscopy and fluorescence lifetime imaging microscopy (FLIM) to assess cellular metabolism. RESULTS: After intravenous administration of MB at 10-20 mg/kg, it quickly transitioned in the tumor to a colorless leucomethylene blue, with maximum accumulation in the tumor occurring after 5-10 min. A concentration of 10 mg/kg resulted in a relative increase of the tumor oxygenation level for small tumors (volume 50-75 mm3) and normal tissue 120 min after the introduction of MB. A shift in tumor metabolism towards oxidative phosphorylation (according to the lifetime of the NADH coenzyme) was measured using FLIM method after intravenous administration of 10 mg/kg of MB. Intravenous administration of MB at 20 mg/kg results in a long-term decrease in oxygenation, which persisted for at least 120 min after the administration and did not return to its initial level. CONCLUSIONS: Administration of MB at 10 mg/kg shown to increase tumor oxygenation level, potentially leading to more effective antitumor therapy. However, at higher doses (20 mg/kg), MB may cause long-term decrease in oxygenation.

Distribution of various volumes of methylene blue injection in suprainguinal fascia iliaca block under ultrasound guidance: a cadaveric study / Distribución de varios volúmenes de inyección de azul de metileno en el bloque suprainguinal de la fascia ilíaca bajo guía por ultrasonido: un estudio cadavérico

SUMMARY: The local anesthetic volume for a single-shot suprainguinal fascia iliaca block (SFIB) is a key factor of a block success because the courses of the three target nerves from the lumbar plexus (LP), the lateral femoral cutaneous nerve (LFCN), femoral nerve (FN), and obturator nerve (ON), at the inguinal area are isolated and within striking distance. Thus, this cadaveric study aims to demonstrate the distribution of dye staining on the LFCN, FN, ON, and LP following the ultrasound-guided SFIB using 15-50 ml of methylene blue. A total of 40 USG-SFIBs were performed on 20 fresh adult cadavers using 15, 20, 25, 30, 35, 40, 45, and 50 ml of methylene blue. After the injections, the pelvic and inguinal regions were dissected to directly visualize the dye stained on the LFCN, FN, ON, and LP. All FN and LFCN were stained heavily when the 15-50 ml of dye was injected. Higher volumes of dye (40-50 ml) spread more medially and stained on the ON and LP in 60 % of cases. To increase the possibility of dye spreading to all three target nerves and LP of the SFIB, a high volume (≥40 ml) of anesthetic is recommended. If only a blockade of the FN and LFCN is required, a low volume (15-25 ml) of anesthetic is sufficient.

RESUMEN: El volumen de anestésico local para un bloqueo de la fascia ilíaca suprainguinal (FISI) de una sola inyección es un factor clave para el éxito del bloqueo, debido a que los cursos de los tres nervios objetivo del plexo lumbar (PL), el nervio cutáneo femoral lateral (NCFL), femoral (NF) y el nervio obturador (NO), en el área inguinal están aislados y dentro de la distancia de abordaje. Por lo tanto, este estudio cadavérico tiene como objetivo demostrar la distribución de la tinción de tinte en NCFL, NF, NO y PL siguiendo el FISI guiado por ultrasonido usando 15-50 ml de azul de metileno. Se realizaron un total de 40 USG-FISI en 20 cadáveres adultos frescos utilizando 15, 20, 25, 30, 35, 40, 45 y 50 ml de azul de metileno. Después de las inyecciones, se disecaron las regiones pélvica e inguinal para visualizar directamente el tinte teñido en NCFL, NF, NO y PL. Todos los NF y NCFL se tiñeron intensamente cuando se inyectaron los 15- 50 ml de colorante. Volúmenes mayores de colorante (40-50 ml) se esparcen más medialmente y tiñen el NO y la PL en el 60 % de los casos. Para aumentar la posibilidad de que el colorante se propague a los tres nervios objetivo y al PL del FISI, se recomienda un volumen elevado (≥40 ml) de anestésico. Si solo se requiere un bloqueo de NF y NCFL, un volumen bajo (15-25 ml) de anestésico es suficiente.

Developing an analytical method by HPLC for simultaneous quantification of methylene blue and metformin applied to in vitro skin permeation and retention studies.

The aim of this study was to develop an HPLC method for simultaneous quantification of metformin (MET) and methylene blue (MB) in in vitro skin permeation/retention studies, in which retention was evaluated in the different layers of the skin [stratum corneum (SC) and the viable epidermis + dermis (VE + D)]. The method was validated considering the following parameters: specificity, linearity, quantitation limit (LOQ), recovery, precision and accuracy. Calibration curves were obtained using the following six matrices: methanol, water, methanolic extracts from the SC and VE + D spiked with the drugs and drugs extracted from the SC and VE + D. The precision, accuracy and LOQ of the method were evaluated in water and in VE + D and SC, applying the drug extraction process. The results show that the method is selective and linear for both drugs. The precision and accuracy values, independent of matrix and drug, were below the limit of 15%. The LOQ of MB was defined as 0.4 µg/ml in the VE + D and SC and 0.8 µg/ml in water. The LOQ of MET was defined as 0.8 µg/ml in the VE + D and SC and 0.4 µg/ml in the water. The recovery of the method was adequate, consistent and reproducible for the concentration range of 0.4-10 µg/ml for MB (73.3-92.1%) and 0.8-10.0 µg/mL for MET (72.4-94.4%). This method has a potential application in the development of formulation for skin delivery of MB and MET.

Gelatin-loaded cubosomes stabilized with hydrophobically modified quaternized cellulose nanofiber and their pH-dependent release property.

Monoolein cubic phase immobilizing hydrophobically modified gelatin (HmGel) in its water channel was prepared by a melt-hydration method. The cubic phase was micronized into cubosomes by using hydrophobically modified quaternized cellulose nanofiber (HmQCNF) as a stabilizer. The phase transition temperature of the cubic phase was about 68-70 °C. Small angle X-ray diffraction revealed that HmGel-loaded cubosome stabilized with HmCNF was a diamond type of cubic phase. HmGel-loaded cubosomes stailized with HmQCNF were dependent on the pH value in terms of the release of their payload (i.e, methylene blue) much more strongly than HmGel-loaded cubosomes stabilized with Pluronic F127.

Contrasting the efficacy of pulsed dye laser and photodynamic methylene blue nanoemulgel therapy in treating acne vulgaris.

The treatment of acne remains a challenge for dermatologists. A variety of conventional therapies are available for acne treatment such as topical and systemic medications. Although many of these traditional acne treatments are effective, the wide-spread nature of the disease and its sometimes resistant nature delineate the need for alternative therapies. Therefore, over the past decade, phototherapy has been introduced for the treatment of acne, such as pulsed dye lasers (PDLs) and photodynamic therapy (PDT). The aim of this study was to compare the safety and efficacy of PDL and methylene blue-mediated photodynamic therapy (MB-PDT) in the treatment of mild to moderate acne. Split-face clinical trial including fifteen patients presenting with mild to moderate acne were treated with 585 nm PDL on the right side of the face and MB-PDT with 665-nm diode laser on the left side. The photosensitizer MB was prepared in nanoemulgel formulation, and the treatment was carried out for three sessions maximum at 2-weeks intervals. Results revealed that both PDL and MB-PDT were effective therapies in the treatment of acne, as manifested by the reduction of inflammatory and non-inflammatory lesions throughout the treatment period. However, the latter therapy was proven more potent in the reduction of acne severity, and in terms of patients' tolerance. Therefore, it can be concluded that MB in the nanoemulgel form is a promising treatment approach for acne, and can be further experimented in the treatment of other dermatological diseases.

An evaluation of hydromethylthionine as a treatment option for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a major cause of morbidity worldwide and its prevalence is expected to rise. Previous studies involving compounds that target the accumulation of amyloid ß protein have been unsuccessful, renewing interest in therapies directed against intracellular deposits of tau proteins. Derived from methylene blue, hydromethylthionine is a tau aggregation inhibitor that recently emerged as a promising disease-modifying treatment for AD. AREAS COVERED: Herein, the authors cover the chemistry, pharmacodynamics and pharmacokinetics of hydromethylthionine and its oxidized form methylthionine chloride (MTC) that was first studied, as well as clinical efficacy and safety of hydromethylthionine in the treatment of mild to moderate AD. EXPERT OPINION: Randomized clinical trials with hydromethylthionine failed to show any impact of the doses used on the disease course. Data analysis from a non-randomized cohort showed that a smaller dose of the drug previously thought to be ineffective and used as placebo, prescribed as monotherapy rather than as add-on to AD approved symptomatic therapies may slow cognitive decline. This finding was further confirmed by a pharmacokinetic analysis study showing a dose/response relationship with doses around 16 mg daily. Future trials need to study the pharmacological properties of hydromethylthionine and ascertain the optimal safe and effective dose to be used.

Pharmacokinetics and Ex Vivo Antimalarial Activity of Artesunate-Amodiaquine plus Methylene Blue in Healthy Volunteers.

High rates of artemisinin-based combination therapy (ACT) failures in the treatment of Plasmodium falciparum malaria in Southeast Asia have led to triple-drug strategies to extend the useful life of ACTs. In this study, we determined whether methylene blue [MB; 3,7-bis(dimethylamino)phenothiazin-5-ium chloride hydrate] alters the pharmacokinetics of artesunate-amodiaquine (ASAQ) and enhances the ex vivo antimalarial activity of ASAQ. In an open-label, randomized crossover design, a single oral dose of ASAQ (200 mg AS/540 mg AQ) alone or with MB (325 mg) was administered to 15 healthy Vietnamese volunteers. Serial blood samples were collected up to 28 days after dosing. Pharmacokinetic properties of the drugs were determined by noncompartmental analysis. After drug administration, plasma samples from seven participants were assessed for ex vivo antimalarial activity against the artemisinin-sensitive MRA1239 and the artemisinin-resistant MRA1240 P. falciparum lines, in vitro MB significantly increased the mean area under the curve of the active metabolite of AS, dihydroartemisinin (1,246 ± 473 versus 917 ± 405 ng·h/ml, P = 0.009) but did not alter the pharmacokinetics of AQ, AS, or desethylamodiaquine. Comparing the antimalarial activities of the plasma samples from the participants collected up to 48 h after ASAQ plus MB (ASAQ+MB) and ASAQ dosing against the MRA1239 and MRA1240 lines, MB significantly enhanced the blood schizontocidal activity of ASAQ by 2.0-fold and 1.9-fold, respectively. The ring-stage survival assay also confirmed that MB enhanced the ex vivo antimalarial activity of ASAQ against MRA1240 by 2.9-fold to 3.8-fold, suggesting that the triple-drug combination has the potential to treat artemisinin-resistant malaria and for malaria elimination. (This study has been registered in the Australian New Zealand Clinical Trials Registry [https://anzctr.org.au/] under registration number ACTRN12612001298808.).

Modulation of release mechanisms of methylene blue (MB) monomers and dimers from silica-MB@shellac synthesized by antisolvent crystallization.

Release behaviors of drugs from drug deliveries are crucial for the enhancement of therapy efficiency, reduction of toxicity and patient compliance. Herein, antisolvent crystallization is employed to coat methlyene blue (MB)-loaded silica by shellac precipitation (silica-MB@shellac), which is simultaneously induced by outward diffusion of H+ ions from particular silica-MB. The encapsulation of shellac shell on silica-MB modulates the aggregation state of MB, which endows silica-MB@shellac a decreased MB's thermal stability, enhanced photoluminescence intensity, improved stability against in vitro reduction by ascorbic acid and retained photodynamic therapy activity. From the absorbance of MB supernatant obtained during incubation, the concentrations of MB monomers and dimers are determined via a non-linear regression analysis to investigate the influence of shellac coating on MB's release mechanisms from silica-MB@shellac. According to the simulated models, small diffusion constants of MB are caused by limited diffusion through shellac shells with high compaction degrees. These are observed for samples synthesized under high supersaturation degree during antisolvent crystallization. High degree of supersaturation is achieved through increasing shellac concentration, additive amount and dropping rate of antisolvent, as well as decreasing pH values of aqueous buffers as antisolvent. Furthermore, a combined mechanism of Fickian diffusion and Case-IΙ relaxation is proposed to describe the release behaviors of MB monomer and dimers from silica-MB@shellac. Therefore, this work may shed light on the encapsulation method of polymer on drug-loaded powders and the control of aggregation states of photosensitizers to promote the photoluminescence intensity, photodynamic therapy efficiency and controlled release behaviors.

Optimization of a low pressure plasma process for fabrication of a Drug Delivery System (DDS) for cancer treatment.

A low pressure ICP plasma setup was utilized to deposit thin organic barrier coatings on various substrates to fabricate DDS with encapsulated Carboplatin as a drug and Methylene Blue as a drug model. Choice of the substrates and optimal plasma parameters were discussed for the fabrication of DDS with required characteristics. Prepared thin films were analysed by FTIR, SEM, and the barrier properties were studied by measuring drug concentration released into the medium by UV-VIS and ICP-MS techniques.

Anatomical description of anaesthetic spread after deep erector spinae block at L-4. / Estudio anatómico de la distribución del volumen administrado tras bloqueo en el plano profundo del erector espinal a nivel lumbar.

INTRODUCTION: Thoracic erector spinae plane (ESP) block is now used for postoperative analgesia. However, although reports of lumbar ESP have been published, the anesthetic spread and mechanism of action of this technique remains unclear. We describe the lumbar ESP block technique and evaluate the spread of 20ml of solution administered at the level of the transverse process of L4 in a cadaver model. METHODS: Observational study after 12 lumbar ESP blocks at L4 on a fresh cadaver model (6 bilaterally). The spread of 20ml of injected contrast solution was assessed by computed tomography in all 6 samples. Four of the samples were evaluated by anatomical study, 2 by plane dissection, and 2 others were frozen and cut into 2-2.5cm axial slices. RESULTS: The injected solution spread from L2 to L5 in a cranio-caudal direction in the erector spinae muscle, reaching the facet joints medially and the thoracolumbar fascia laterally. In 33% of cases the solution did not spread anterior to the transverse process; in 51%, spread was minimal and did not affect the corresponding spinal nerves, and in 2 samples (16%), spread was extensive and reached the corresponding spinal nerves. CONCLUSIONS: Lumbar ESP at L4 always acts on the posterior branches of the spinal nerves, but seldom spreads to the paravertebral space to block the spinal nerve.

Inactivation kinetics and lethal dose analysis of antimicrobial blue light and photodynamic therapy.

BACKGROUND: Antimicrobial Photodynamic therapy (A-PDT) has been used to treat infections. Currently, microbial inactivation data is reported presenting survival fraction averages and standard errors as discrete points instead of a continuous curve of inactivation kinetics. Standardization of this approach would allow clinical protocols to be introduced globally, instead of the piecemeal situation which currently applies. METHODS: To this end, we used a power-law function to fit inactivation kinetics and directly report values of lethal doses (LD) and a tolerance factor (T) that informs if inactivation rate varies along the irradiation procedure. A deduced formula was also tested to predict LD for any given survival fraction value. We analyzed the photoantimicrobial effect caused by red light activation of methylene blue (MB-APDT) and by blue light (BL) activation of endogenous microbial pigments against 5 clinically relevant pathogens. RESULTS: Following MB- APDT, Escherichia coli and Staphylococcus aureus cells become increasingly more tolerant to inactivation along the irradiation process (T < 1). Klebsiella pneumoniae presents opposite behavior, i.e., more inactivation is observed towards the end of the process (T > 1). P. aeruginosa and Candida albicans present constant inactivation rate (T˜1). In contrast, all bacterial species presented similar behavior during inactivation caused by BL, i.e., continuously becoming more sensitive to blue light exposure (T > 1). CONCLUSION: The power-law function successfully fit all experimental data. Our proposed method precisely predicted LD and T values. We expect that these analytical models may contribute to more standardized methods for comparisons of photodynamic inactivation efficiencies.

Fluorescence Polarization of Methylene Blue as a Quantitative Marker of Breast Cancer at the Cellular Level.

A quantitative technique to detect cancer in single cells could transform cancer diagnosis. Current cancer diagnosis utilizes histopathology, which requires tissue acquisition, extensive processing and, in most cases, relies on the qualitative morphological analysis of tissues and cells. Molecular biomarkers are only available for a few specific tumor subtypes. We discovered that the fluorescence polarization (Fpol) of Methylene Blue (MB) is significantly higher in cancer than in normal human breast tissues and cells. We confirmed that fluorescence polarization imaging did not affect the viability of the cells and yielded highly significant differences between cancer and normal cells using MB concentrations as low as 0.05 and 0.01 mg/ml. To explain this phenomenon we examined intracellular localization of MB and its fluorescence lifetime. We determined that higher fluorescence polarization of MB occurs due to its increased accumulation in mitochondria of cancer cells, as well as shorter fluorescence lifetime in cancer relative to normal cells. As quantitative MB Fpol imaging can be performed in vivo and in real time, it holds the potential to provide an accurate quantitative marker of cancer at the cellular level.

Methylene blue does not bypass Complex III antimycin block in mouse brain mitochondria.

Methylene blue (MB) is a promising prodrug to treat mitochondrial dysfunctions that is currently being used in clinical trials for Alzheimer's disease. MB can penetrate the blood brain barrier, accumulating in brain mitochondria where it acts as a redox mediator in the electron transfer chain (ETC). Mitochondrial flavins are thought to reduce MB, which is then oxidized by cytochrome c, thereby bypassing inhibited Complex I of ETC. We found that in mouse brain mitochondria, MB fails to restore the membrane potential and respiration inhibited by antimycin. Furthermore, antimycin inhibits MB-induced H2 O2 generation. Our data suggest that the acceptor of electrons from MB is a Qo ubiquinol-binding site of Complex III; thus, MB-based drugs might not be helpful in mitochondrial dysfunctions involving Complex III inhibition.

Methylene Blue-Fortified Molybdenum Trioxide Nanoparticles: Harnessing Radical Scavenging Property.

A hybrid nanosystem with impeccable cellular imaging and antioxidant functionality is demonstrated. The microwave irradiation-derived molybdenum trioxide nanoparticles (MoO3 NPs) were surface-functionalized with the cationic dye molecule, methylene blue (MB), which enables superior UV-visible absorbance and fluorescence emission wavelengths potential for bioimaging. The radical scavenging property of the pristine MoO3 NPs and MoO3-MB NPs were studied in vivo using Caenorhabditis elegans as the model system. Heat shock-induced oxidative stress in C. elegans was significantly resolved by the MoO3-MB NPs, in agreement with the in vitro radical scavenging study by electron paramagnetic resonance spectroscopy. Hybrid nanostructures of MoO3-MB demonstrate synergistic benefits in intracellular imaging with intrinsic biocompatibility and antioxidant behavior, which can facilitate application as advanced healthcare materials toward bioimaging and clinical therapeutics.

Methylene Blue for Refractory Shock in Polytraumatized Patient: A Case Report.

BACKGROUND: Methylene blue (MB) has been advocated for the treatment of shock refractory to standard measures. MB is proposed to increase blood pressure in shock by interfering with guanylate cyclase and nitric oxide synthase (NOS) activity. Several studies have evaluated the vasoconstrictive and positive inotropic effects of MB in septic shock patients. However, there is a paucity of studies involving trauma patients. CASE REPORT: A 4-year-old boy was hit by a truck while riding his bicycle and was treated with fluid resuscitation at the emergency department and then taken to the operating room for damage-control surgery. He had liver, diaphragm, rectal, and thoracic injuries. At the pediatric intensive care unit (PICU), he remained hypotensive despite volume, dopamine, epinephrine, and norepinephrine infusion. A dose of 0.5 mg/kg of i.v. MB was administered. During the next 2 h after MB administration, we were able to wean him off norepinephrine, and doses of epinephrine and dopamine were reduced. Ultimately, he was discharged from the PICU 13 days later in good condition. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Trauma patients who have experienced bleeding and survived the initial insult are still at risk of dying from continuing systemic hypoperfusion and the resultant multiple organ dysfunctions. Use of a low dose of MB as an adjuvant to treat shock might improve survival of these patients.

Methylene blue MMX® tablets for chromoendoscopy. Bioavailability, colon staining and safety in healthy volunteers undergoing a full colonoscopy.

Methylene blue-MMX® tablets are proposed as an aid for detection and visualisation of adenomas and carcinomas in patients undergoing colonoscopy, by improving their detection rate and highlighting the presence of the intestinal dysplastic lesions. Single total doses of 100 and 200 mg were administered to healthy volunteers undergoing a bowel cleansing preparation and a full colonoscopy to investigate the colonic staining. The pharmacokinetics of methylene blue and the safety after exposure to the tablets were also investigated. With 200 mg, the best staining, assessed as the sum of acceptable and good staining, was achieved in the ascending colon and rectosigmoid (75% subjects each), the transverse and the descending colon (approximately 63% each). Absence of staining or overstaining were reported for no colonic region of interest in any subject. Similar results were observed in the 100 mg dose group. Methylene blue blood concentrations reached a peak (Cmax) in a median time (Tmax) of 12 h with 100 mg and 16 h with 200 mg. AUC0-t was 10.7 ±â€¯6.7 µg/mLxh after 100 mg and 25.2 ±â€¯7.4 µg/mLxh after 200 mg. Half-life ranged between 9 and 22 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative urinary excretion was about 28% after 100 mg and about 39% after 200 mg up to 60 h post-dose. The overall frequency of adverse events after single dose of the test product administered along with a bowel cleansing preparation was 39%, but only one was related to the test product: abnormal transaminases. The most frequent adverse event was a transient polyuria (17%). One serious adverse event (gastrointestinal haemorrhage) led the subject to study discontinuation and hospitalisation and another subject withdrew the study due to one adverse event (haematemesis). Either event was not related to methylene blue.

Nootropic nanocomplex with enhanced blood-brain barrier permeability for treatment of traumatic brain injury-associated neurodegeneration.

Traumatic brain injury (TBI) is an intracranial injury which can induce immediate neuroinflammation and long-term neurological deficits. Methylene blue (MB) as a nootropic has a great potential to treat neurodegeneration after TBI because of its anti-inflmmatory and neuroprotective functions. However, its limited accumulation to the brain across the blood-brain barrier (BBB) remains a major hurdle to be overcome. In this paper, we present a polymer surfactant-encapsulated nanocomplex of MB as a delivery system with high BBB permeability for efficacious treatment of TBI-induced neurodegeneration. MB was formulated via electrostatically/hydrophobically directed assembly with fatty acid and Pluronic surfactant (F-127 or F-68) to construct nanocomplexes of two different colloidal sizes (<10 nm and ~108 nm in hydrodynamic diameter for NanoMB-127 and NanoMB-68, respectively). Compared to uncomplexed free MB, formulation into the ultrasmall nanocomplex (NanoMB-127) significantly enhanced the uptake of MB by blood-brain vascular endothelial bEnd3 cells in vitro, and indeed improved its BBB penetration upon systemic administration to normal mice in vivo. However, large-size NanoMB-68 showed negligible BBB crossing despite the efficient bEnd3 cell internalization in vitro, probably due to the unfavorable pharmacokinetic profile associated with its large particle size. By virtue of the efficient BBB penetration and cellular uptake, ultrasmall NanoMB-127 was shown to distinctively reduce the expression level of an inflammatory cytokine with no notable toxicity in vitro and also considerably prevent the neurodegeneration after TBI in mice at much lower doses than free MB. Overall, the Pluronic-supported nanocomplexation method allows efficient brain delivery of MB, offering a novel way of enhancing the efficacy of neurotherapeutics to treat brain diseases.

A novel HIPEC technique using hybrid CO2 recirculation system: intra-abdominal diffusion test in a porcine model.

The role of loco-regional treatment of peritoneal carcinomatosis using intraperitoneal chemotherapy is still investigated. Actually, new technologies are suitable for these procedures, especially a new hybrid system using CO2 called Peritoneal Recirculation System (PRS-1.0 Combat). A HIPEC procedure in a porcine model using the PRS system was conducted. The objective of experimentation was to assess the distribution of liquid inside the abdomen, by using methylene blue instead of chemotherapy. Moreover, we positioned six different thermal probes in different abdominal regions inside the abdomen to measure the temperature during procedure. During the procedure, all thermal probes recorded an average temperature of 41.5°. At the end of infusion, the abdomen was emptied and then opened; the tracer distribution was recorded. No technical problems were recorded during the procedure. Good distribution of tracer was recorded. More studies are needed to investigate better this new technology.

Qualitative and quantitative analysis of lateral diffusion of drugs in human skin.

This study aimed to qualitatively and quantitatively analyze lateral diffusion of drugs in dermatomed human skin. Lateral diffusion of calcein and methylene blue dyes in skin was investigated using confocal laser microscopy, calcein imaging, and histology studies. In in vitro permeation studies, two linear microdialysis probes were inserted into the dermis of untreated, poly lacto-glycolic acid microneedle-treated, and ablative laser-treated skin such that one was in the center of the diffusion area and the other was parallel, at 8 mm from the central probe. Skin was mounted on Franz cells, sandwiched between donor containing diclofenac sodium solution and receptor containing phosphate buffered saline, pH 7.4. Qualitative techniques revealed faster lateral diffusion of the dyes in microneedle-treated skin than laser-treated skin. Rate of drug diffusion in the central probe in the microneedle-treated skin (11.8 ±â€¯2.5 µg/h) was significantly higher than untreated and laser-treated skin (p  <  0.05). Rate of lateral diffusion in untreated group (0.7 ±â€¯0.1 µg/h) was significantly lower than microneedle and laser-treated skin (p  <  0.05). Overall, in vitro microdialysis was demonstrated as a novel and valuable tool that can be employed for quantitative investigation of rate of vertical and lateral diffusion of drugs in intact and microporated skin.