Hyperthermia Improves Solubility of Intravesical Chemotherapeutic Agents

2020 ◽  
Vol 6 (4) ◽  
pp. 461-470
Author(s):  
Dominic C. Grimberg ◽  
Ankeet Shah ◽  
Wei Phin Tan ◽  
Wiguins Etienne ◽  
Ivan Spasojevic ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mitomycin C ◽  
Room Temperature ◽  
Chemotherapeutic Agents ◽  
Intravesical Chemotherapy ◽  
Response To Treatment ◽  
Intravesical Therapy ◽  
Recurrence Rates ◽  
Urine Ph ◽  
Improve Drug Delivery

BACKGROUND: Nearly 70% of all new cases of bladder cancer are non-muscle invasive disease, the treatment for which includes transurethral resection followed by intravesical therapy. Unfortunately, recurrence rates approach 50% in part due to poor intravesical drug delivery. Hyperthermia is frequently used as an adjunct to intravesical chemotherapy to improve drug delivery and response to treatment. OBJECTIVE: To assess the solubility profile of intravesical chemotherapies under varying conditions of pH and temperature. METHODS: Using microplate laser nephelometry we measured the solubility of three intravesical chemotherapy agents (mitomycin C, gemcitabine, and cisplatin) at varying physical conditions. Drugs were assessed at room temperature (23°C), body temperature (37°C), and 43°C, the temperature used for hyperthermic intravesical treatments. To account for variations in urine pH, solubility was also investigated at pH 4.00, 6.00, and 8.00. RESULTS: Heat incrementally increased the solubility of all three drugs studied. Conversely, pH largely did not impact solubility aside for gemcitabine which showed slightly reduced solubility at pH 8.00 versus 6.00 or 4.00. Mitomycin C at the commonly used 2.0 mg/mL was insoluble at room temperature, but soluble at both 37 and 43°C. CONCLUSIONS: Hyperthermia as an adjunct to intravesical treatment would improve drug solubility, and likely drug delivery as some current regimens are insoluble without heat. Improvements in solubility also allow for testing of alternative administration regimens to improve drug delivery or tolerability. Further studies are needed to confirm that improvements in solubility result in increased drug delivery.

scholarly journals Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 288 ◽  
Author(s):  
Mohamed Haider ◽  
Shifaa M. Abdin ◽  
Leena Kamal ◽  
Gorka Orive
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Room Temperature ◽  
Drug Loading ◽  
Physical Stability ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
Nanostructured Lipid Carriers ◽  
Solid Matrix ◽  
Current Standard

The efficacy of current standard chemotherapy is suboptimal due to the poor solubility and short half-lives of chemotherapeutic agents, as well as their high toxicity and lack of specificity which may result in severe side effects, noncompliance and patient inconvenience. The application of nanotechnology has revolutionized the pharmaceutical industry and attracted increasing attention as a significant means for optimizing the delivery of chemotherapeutic agents and enhancing their efficiency and safety profiles. Nanostructured lipid carriers (NLCs) are lipid-based formulations that have been broadly studied as drug delivery systems. They have a solid matrix at room temperature and are considered superior to many other traditional lipid-based nanocarriers such as nanoemulsions, liposomes and solid lipid nanoparticles (SLNs) due to their enhanced physical stability, improved drug loading capacity, and biocompatibility. This review focuses on the latest advances in the use of NLCs as drug delivery systems and their preparation and characterization techniques with special emphasis on their applications as delivery systems for chemotherapeutic agents and different strategies for their use in tumor targeting.

scholarly journals The use of chemotherapeutics for the treatment of keloid scars

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Christopher David Jones ◽  
Luke Guiot ◽  
Mike Samy ◽  
Mark Gorman ◽  
Hamid Tehrani
Keyword(s):  
Mitomycin C ◽  
Steroid Injection ◽  
Combined Therapy ◽  
Surgical Excision ◽  
Chemotherapeutic Agents ◽  
Treatment Modalities ◽  
Success Rates ◽  
Recurrence Rates ◽  
Cutaneous Injury ◽  
Keloid Scars

Keloid scars are pathological scars, which develop as a result of exaggerated dermal tissue proliferation following cutaneous injury and often cause physical, psychological and cosmetic problems. Various theories regarding keloidogenesis exist, however the precise pathophysiological events remain unclear. Many different treatment modalities have been implicated in their management, but currently there is no entirely satisfactory method for treating all keloid lesions. We review a number of different chemotherapeutic agents which have been proposed for the treatment of keloid and hypertrophic scars while giving insight into some of the novel chemotherapeutic drugs which are currently being investigated. Non-randomized trials evaluating the influence of different chemotherapeutic agents, such as 5-fluorouracil (5-FU); mitomycin C; bleomycin and steroid injection, either alone or in combination with other chemotherapeutic agents or alternative treatment modalities, for the treatment of keloids were identified using a predefined PubMed search strategy. Twenty seven papers were identified. Scar improvement ≥50% was found in the majority of cases treated with 5-FU, with similar results found for mitomycin C, bleomycin and steroid injection. Combined intralesional 5-FU and steroid injection produced statistically significant improvements when compared to monotherapy. Monotherapy recurrence rates ranged from 0-47% for 5-FU, 0-15% for bleomycin and 0-50% for steroid injection. However, combined therapy in the form of surgical excision and adjuvant 5-FU or steroid injections demonstrated lower recurrence rates; 19% and 6% respectively. Currently, most of the literature supports the use of combination therapy (usually surgery and adjuvant chemotherapy) as the mainstay treatment of keloids, however further investigation is necessary to determine success rates over longer time frames. Furthermore, there is the potential for novel therapies, but further investigation is required to elucidate their true efficacy.

Design of Lipophilic Prodrugs to Improve Drug Delivery and Efficacy

2016 ◽  
Vol 17 (15) ◽  
pp. 1773-1798 ◽  
Author(s):  
Abhirup Mandal ◽  
Mitesh Patel ◽  
Ye Sheng ◽  
Ashim K. Mitra
Keyword(s):  
Drug Delivery ◽  
Lipophilic Prodrugs ◽  
Improve Drug Delivery

scholarly journals Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Vol 10 (9) ◽  
pp. 1926
Author(s):  
Hiroto Inaba ◽  
Ching-Hon Pui
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Detailed Analysis ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Therapeutic Implications

The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.

Studies on drug-assisted silver nanoparticles to reduce granulocytopenia and improve drug delivery for cancer therapy

2021 ◽  
Vol 127 (5) ◽  
Author(s):  
Chetan Chavan ◽  
Saniya Prabhune ◽  
Siddhi Shedge ◽  
Rajashree Patwardhan ◽  
Sagar Kamble ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Silver Nanoparticles ◽  
Cancer Therapy ◽  
Improve Drug Delivery

scholarly journals Mitomycin c intravesical therapy in noninvasive bladder cancer after failure on thiotepa

Cancer ◽  
1984 ◽  
Vol 53 (5) ◽  
pp. 1025-1028 ◽  
Author(s):  
Brian F. Issell ◽  
George R. Prout ◽  
Mark S. Soloway ◽  
Kenneth B. Cummings ◽  
George Brannen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mitomycin C ◽  
Intravesical Therapy

scholarly journals Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Raft Polymerization ◽  
Chemotherapeutic Agents ◽  
Polymer Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Molecular Weights ◽  
Delivery Vehicles ◽  
Targeted Drug

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.

scholarly journals Synthesis of mucoadhesive thiol-bearing microgels from 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate: novel drug delivery systems for chemotherapeutic agents to the bladder

2015 ◽  
Vol 3 (32) ◽  
pp. 6599-6604 ◽  
Author(s):  
M. T. Cook ◽  
S. A. Schmidt ◽  
E. Lee ◽  
W. Samprasit ◽  
P. Opanasopit ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
Novel Drug

Thiol-bearing microgels have been synthesised from copolymerisation of 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate, and subsequent deprotection using sodium thiomethoxide.

scholarly journals Bladder perforation after immediate postoperative intravesical instillation of mitomycin C

2013 ◽  
Vol 4 (1) ◽  
pp. 1 ◽  
Author(s):  
Darwin Lim ◽  
Jonathan I. Izawa ◽  
Paul Middlebrook ◽  
Joseph L. Chin
Keyword(s):  
Intensive Care ◽  
Single Dose ◽  
Mitomycin C ◽  
Male Patient ◽  
Transurethral Resection ◽  
Bladder Carcinoma ◽  
Adjunctive Therapy ◽  
Intravesical Instillation ◽  
Recurrence Rates ◽  
Superficial Bladder Carcinoma

Intravesical chemotherapy after transurethral resection of a bladdertumour (TURBT) has been observed to significantly decreaserecurrence rates compared to TURBT alone. Though immediatepostoperative intravesical treatment with chemotherapeutic agentsafter transurethral resection for superficial bladder carcinoma isgenerally considered a safe and effective adjunctive therapy indecreasing recurrence rates, its instillation is not always completelyinnocuous. Lately, a more serious complication of bladderperforation associated with immediate instillation of intravesicalmitomycin C (MMC) after TURBT was reported. We reportour own experience of a male patient with bladder perforationafter an early instillation of a single dose of MMC. In this case,systemic toxicity occurred which required intensive care aftersurgical repair.

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