Hyperthermia, bladder pressure, and intravesical drug delivery.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 469-469
Author(s):  
Dominic C. Grimberg ◽  
Scott P. Campbell ◽  
Wiguins Etienne ◽  
Ping Fan ◽  
Paolo F. Maccarini ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Linear Regression ◽  
Drug Concentration ◽  
Dwell Time ◽  
Bladder Wall ◽  
Foley Catheter ◽  
Bladder Pressure ◽  
Bathing Solution ◽  
Target Tissue ◽  
Bladder Temperature

469 Background: Little is known about the pharmacokinetics of intravesical chemotherapies. Various parameters can be altered including temperature, dwell time, drug concentration, and bladder pressure. Here, we hypothesize that increasing bladder pressure during instillation will improve drug delivery. Methods: An ex-vivo porcine model was developed to evaluate determinants of drug penetration into the bladder wall. Porcine bladders were suspended in isotonic saline at 37°C with a three-way Foley catheter in the bladder. Temperature probes were positioned in the extravesical bathing solution, bladder lumen, and sutured to the detrusor to ensure maintenance of desired temperatures. 2g gemcitabine in 100mL normal saline was heated to 43°C and circulated through the bladder using the Combat Bladder Recirculation System. Bladder pressures were monitored throughout each trial. After 60 minutes of dwell time, rapid dissection was performed to obtain full-thickness bladder samples from the bladder dome, posterior wall, trigone, and left and right lateral walls. Tissue was homogenized and liquid chromatography with tandem mass spectrometry (LC/MS/MS) was performed to measure gemcitabine concentration within the bladder wall. Linear regression and Pearson correlation were performed to determine the association between mean bladder pressure during instillation and drug concentration within the bladder wall. Multiple linear regression was conducted to control for bladder location and thickness. Results: Gemcitabine concentration within the bladder wall was measured 25 times across five trials. Mean gemcitabine concentration within bladder wall was 3.68 mg/g (sd 1.35). Pressure ranged from 149.8 mmHg to 277.7 mmHg (mean 194.8, sd 22.0). On univariate analysis, higher pressure was associated with increased gemcitabine concentration within the bladder wall (correlation = 0.49, p = 0.013). This result persisted after adjusting for bladder location (ß = 0.49, p = 0.006) and thickness (ß = 0.70, p = 0.03). Unstandardized regression coefficient in each of the models was 0.099 (mmHg x g)/mg, demonstrating that for each pressure increase of 10mmHg there was an associated increase in gemcitabine concentration of approximately 1 mg/g (Table). Conclusions: Data suggest that bladder pressure dramatically improves the extent of gemcitabine penetration into the bladder wall. Future research is needed to evaluate the therapeutic effect of increased gemcitabine delivery to target tissue in patients with bladder cancer. [Table: see text]

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

Bridging the Gap of Drug Delivery in Colon Cancer: The Role of Chitosan and Pectin Based Nanocarriers System

2020 ◽  
Vol 17 (10) ◽  
pp. 911-924
Author(s):  
Rohitas Deshmukh
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Therapeutic Agent ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Target Tissue ◽  
Polymer Carriers

Colon cancer is one of the most prevalent diseases, and traditional chemotherapy has not been proven beneficial in its treatment. It ranks second in terms of mortality due to all cancers for all ages. Lack of selectivity and poor biodistribution are the biggest challenges in developing potential therapeutic agents for the treatment of colon cancer. Nanoparticles hold enormous prospects as an effective drug delivery system. The delivery systems employing the use of polymers, such as chitosan and pectin as carrier molecules, ensure the maximum absorption of the drug, reduce unwanted side effects and also offer protection to the therapeutic agent from quick clearance or degradation, thus allowing an increased amount of the drug to reach the target tissue or cells. In this systematic review of published literature, the author aimed to assess the role of chitosan and pectin as polymer-carriers in colon targeted delivery of drugs in colon cancer therapy. This review summarizes the various studies employing the use of chitosan and pectin in colon targeted drug delivery systems.

Role of sympathetic innervation in the feline continence process under natural filling conditions

1992 ◽  
Vol 68 (5) ◽  
pp. 1842-1849 ◽  
Author(s):  
C. W. Vaughan ◽  
P. M. Satchell
Keyword(s):  
Sympathetic Innervation ◽  
Bladder Wall ◽  
Bladder Pressure ◽  
Detrusor Muscle ◽  
Wall Tension ◽  
Natural Rate ◽  
Hypogastric Nerve ◽  
Selective Blockade ◽  
Change In The Mean ◽  
The Mean

1. The effect of the sympathetic innervation on the bladder detrusor muscle was assessed in pentobarbitone-anesthetized cats by measuring the changes in bladder wall tension that occurred during sympathetic ganglion blockade after filling the bladder at a natural rate. 2. At a point 60% of the way through the continence process, systemic sympathetic blockade was produced by intravenous trimethaphan, and selective blockade of postganglionic hypogastric nerve activity was produced by application of trimethaphan to the exposed inferior mesenteric ganglia. The level of blockade was monitored with an in-continuity hypogastric nerve recording. 3. During both systemic and selective ganglion blockade, there was an increase in baseline transmural bladder pressure and a decrease in the amplitude of nonmicturating contractions. 4. Although there was no change in the mean level of transmural bladder pressure during either systemic or selective blockade, there was a significant increase in the mean level of bladder wall mechanoreceptor discharge, suggesting that before the blockade sympathoinhibitory effects were greater than sympathoexcitatory effects. 5. Measurement of bladder wall mechanoreceptor discharge before and during ganglion blockade revealed a net sympathoinhibitory influence on the level of bladder wall tension under natural filling conditions. These results confirm that the detrusor muscle of the feline bladder is under both sympathoinhibitory and sympathoexcitatory influences for a significant portion of the continence process.

Magnetite mesoporous silica nanoparticles embedded in carboxybetaine methacrylate for application in hyperthermia and drug delivery

2020 ◽  
Vol 44 (20) ◽  
pp. 8232-8240 ◽  
Author(s):  
Hasan Keshavarz ◽  
Alireza Khavandi ◽  
Somaye Alamolhoda ◽  
M. Reza Naimi-Jamal
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Protein Corona ◽  
Target Tissue ◽  
Burst Effect

Magnetite mesoporous silica nanoparticles (MMSNs) are biocompatible and can easily deliver a drug to the target tissue, but there are two challenges: burst effect and protein corona.

Afterhyperpolarization Current in Myenteric Neurons of the Guinea Pig Duodenum

2001 ◽  
Vol 85 (5) ◽  
pp. 1941-1951 ◽  
Author(s):  
Fivos Vogalis ◽  
John B. Furness ◽  
Wolf A. A. Kunze
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Dwell Time ◽  
High Probability ◽  
Resting Potential ◽  
Bathing Solution ◽  
Inward Current ◽  
Current Pulses ◽  
Mean Variance ◽  
Small Conductance

Whole cell patch and cell-attached recordings were obtained from neurons in intact ganglia of the myenteric plexus of the guinea pig duodenum. Two classes of neuron were identified electrophysiologically: phasically firing AH neurons that had a pronounced slow afterhyperpolarization (AHP) and tonically firing S neurons that lacked a slow AHP. We investigated the properties of the slow AHP and the underlying current ( I AHP) to address the roles of Ca2+ entry and Ca2+ release in the AHP and the characteristics of the K+channels that are activated. AH neurons had a resting potential of −54 mV and the AHP, which followed a volley of three suprathreshold depolarizing current pulses delivered at 50 Hz through the pipette, averaged 11 mV at its peak, which occurred 0.5–1 s following the stimulus. The duration of these AHPs averaged 7 s. Under voltage-clamp conditions, I AHP's were recorded at holding potentials of −50 to −65 mV, following brief depolarization of AH neurons (20–100 ms) to positive potentials (+35 to +50 mV). The null potential of the I AHP at its peak was −89 mV. The AHP and I AHP were largely blocked by ω-conotoxin GVIA (0.6–1 μM). Both events were markedly decreased by caffeine (2–5 mM) and by ryanodine (10–20 μM) added to the bathing solution. Pharmacological suppression of the I AHP with TEA (20 mM) or charybdotoxin (50–100 nM) unmasked an early transient inward current at −55 mV following step depolarization that reversed at −34 mV and was inhibited by niflumic acid (50–100 μM). Mean-variance analysis performed on the decay of the I AHPrevealed that the AHP K+ channels have a mean chord conductance of ∼10 pS, and there are ∼4,000 per AH neuron. Spectral analysis showed that the AHP channels have a mean open dwell time of 2.8 ms. Cell-attached patch recordings from AH neurons confirmed that the channels that open following action currents have a small unitary conductance (10–17 pS) and open with a high probability (≤0.5) within the first 2 s following an action potential. These results indicate that the AHP is largely a consequence of Ca2+ entry through ω-conotoxin GVIA-sensitive Ca2+ channels during the action potential, Ca2+-triggered Ca2+ release from caffeine-sensitive stores and the opening of Ca2+-sensitive small-conductance K+ channels.

Gastro-retentive drug delivery system for treatment of Ulcer

2019 ◽  
Vol 3 (02) ◽  
pp. 203-210
Author(s):  
Mohd Vaseem Fateh ◽  
Vikas Kumar ◽  
Renu Chaudhary ◽  
Vivak Ujjwal
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Sustained Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Concentration ◽  
Oral Dosage ◽  
Oral Drug ◽  
Time Duration ◽  
Release Drug

Due to the comfort of administration, economical and extensibility in formulation, the most adopted route to the systemic circulation is the oral route regardless of the astounding elevation in the drug delivery. Oral drug delivery is the most comforting method of delivery due to its comforting method of delivery, due to its better solubility, accurate dosage and simpler production. Approximately 90% of the drugs are administered orally of which solid oral dosage form is the most chosen class of medicaments. Conventional dosage forms usually exhibit the serum drug concentration fluctuations and irregularities in drug concentration in the tissues with resultant toxicity, low bioavailability and thus low therapeutic effects. Accordingly, the concept of the oral sustained release drug delivery system has gained popularity in advancement. Sustained release drug deliveries have steady and consistent drug release over longer time duration. Here, if the drug release is consistent over the time duration, it is supposed to be controlled release system, however if the system doesn’t achieve the constant drug release but shows the drug release over the longer duration compared to the conventional system, it is prolonged release systems. These systems are hot in the recent trend as they offer huge designing and adaptability range during formulation

J0203-2-1 Transvascular drug delivery to target tissue by the use of photomechanical waves

2010 ◽  
Vol 2010.6 (0) ◽  
pp. 175-176
Author(s):  
Shunichi SATO ◽  
Ken YOSHIDA ◽  
Mitsuhiro TERAKAWA ◽  
Hiroshi ASHIDA
Keyword(s):  
Drug Delivery ◽  
Target Tissue

scholarly journals Emphysematous Cystitis Occurred in the Case Treated with Steroid for Autoimmune Hepatitis

2013 ◽  
Vol 2013 ◽  
pp. 1-3
Author(s):  
Tateki Yoshino ◽  
Shinya Ohara ◽  
Hiroyuki Moriyama
Keyword(s):  
Blood Culture ◽  
Autoimmune Hepatitis ◽  
Complete Blood Count ◽  
Bladder Wall ◽  
Foley Catheter ◽  
C Reactive Protein ◽  
Laboratory Examination ◽  
Emphysematous Cystitis ◽  
Reactive Protein ◽  
Wbc Count

Emphysematous cystitis is a rare clinically entity, more commonly seen in diabetic, immunocompromised patients, which was characterized by air within the bladder wall and lumen. A 83-year-old woman was introduced to our department with fever elevation and abnormal findings of computed tomography (CT). She took orally prednisolone for autoimmune hepatitis. Pelvic CT revealed diffuse air throughout the bladder wall. Urinalysis showed combined hematuria and pyuria.Escherichia coliwas detected in blood culture. Abnormal findings of complete blood count and laboratory examination included an elevated WBC count (12,200/L), C-reactive protein (11.7 mg/dL), and creatinine (1.07 mg/dL). Cystoscopy confirmed diffuse submucosal emphysema throughout. On the basis of diagnosis with emphysematous cystitis, she was treated with antibiotics based on the results of blood culture and indwelling Foley catheter. After treatment, the improvement of inflammatory findings and submucosal emphysema on cystoscopy and CT were achieved.

scholarly journals Traditional, unfairly forgotten, rarely used and promising drug delivery methods in ophthalmology: a clinical interpretation (part 1)

2019 ◽  
Vol 12 (2) ◽  
pp. 83-95 ◽  
Author(s):  
A. V. Kuroyedov ◽  
V. V. Brzhesky ◽  
E. A. Krinitsyna
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Drug Concentration ◽  
Targeted Drug Delivery ◽  
Anatomical Structure ◽  
Delivery Methods ◽  
Clinical Interpretation ◽  
Physiological Properties ◽  
Challenging Tasks ◽  
Targeted Drug

Ocular targeted drug delivery is one of the most challenging tasks for pharmaceutical researchers and practical ophthalmologists. The possibilities of drug delivery to the eye are naturally determined by the anatomical structure of the eye and its physiological properties, which restrict the period when therapeutically required drug concentration could be maintained. Combined drug delivery schemes may, potentially, improve the patient’s acceptance of treatment, reduce side effects, increase efficacy, and eventually preserve vision.

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