The physical and chemical stability of cisplatin (Teva) in concentrate and diluted in sodium chloride 0.9%

Karbownik, Agnieszka; Szałek, Edyta; Urjasz, Hanna; Głęboka, Aleksandra; Mierzwa, Emilia; Grześkowiak, Edmund

doi:10.5114/wo.2012.31775

Cited by 21 publications

(17 citation statements)

References 12 publications

(11 reference statements)

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“…Under each shading condition and a 1000-Lux fluorescent lamp, we examined the amount of remaining CDDP and the pH change. Karbownik et al previously reported that CDDP is stable in saline for 30 days as long as it is not exposed to light [16]. Our results also showed that the amount of remaining CDDP decreased in a time-dependent manner under NSC conditions.…”

Section: Discussionsupporting

confidence: 80%

Effect of different shielding conditions on the stability of Cisplatin

Abe

Matsumoto

Nakayama

et al. 2020

J Pharm Health Care Sci

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Background: Because cisplatin (CDDP) decreases upon light exposure, it is necessary to prevent such exposure during administration. However, the shielding conditions employed are not uniform. Therefore, in this study, we examined the shielding effects of four shading covers, which are commonly used to ensure the stability of CDDP in clinical settings. Methods: Four shielding conditions, along with a control, were tested under a 1000-Lux white fluorescent lamp at room temperature: aluminum foil (Al), brown shading cover (BSC), yellow shading cover (YSC), milky-white antiexposure cover (MAC), and no shading cover (NSC). Under each shielding condition, the relationship between the wavelength and transmittance was monitored in the range of 200-800 nm. CDDP was diluted to three concentration levels: 50, 100, and 250 μg/mL. Furthermore, the amount of remaining CDDP and the pH in the solutions were measured for 120 h. Results: We found that BSC, YSC, and MAC conditions allowed various levels of transmittance; however, Al could not completely transmit light at all wavelengths. Moreover, we showed that the CDDP decreased under MAC and NSC conditions in a time-dependent manner, whereas this decrease was prevented under Al, BSC, and YSC conditions till 120 h. We also demonstrated increases in pH under MAC and NSC conditions in a time-dependent manner, which was prevented under Al, BSC, and YSC conditions till 120 h. Similar results were observed for all three CDDP concentration levels. The results also indicated the approximate relationship between the amount of remaining CDDP and the pH increase. Conclusions: Considering the opacity of each cover, our results suggest that BSC and YSC are useful and effective for minimizing CDDP degradation in clinical settings. Our results also indicate the alternatives for preparing, storing, and administering CDDP in clinical facilities, making the treatment schedule more flexible. Cumulatively, these findings indicate that the use of the appropriate shading covers, such as BSC or YSC, prevents the decrease in CDDP under fluorescent lighting, potentially contributing to achieving its full therapeutic effect.

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Section: Discussionsupporting

confidence: 80%

Effect of different shielding conditions on the stability of Cisplatin

Abe

Matsumoto

Nakayama

et al. 2020

J Pharm Health Care Sci

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“…CP is the most commonly used chemotherapeutic compound, and it was the first approved platinum-containing molecule by the FDA in 1978 [25]. It is stable in ambient conditions [26], and its efficacy has been shown in different types of cancers, including sarcomas, blood vessels, ovarium, testis or different kinds of solid tumors [27]. It crosslinks with the purine bases on the DNA, interferes with DNA repair mechanisms and consequently induces DNA damage in cancer cells [14].…”

Section: Discussionmentioning

confidence: 99%

Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice

et al. 2020

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Cisplatin (CP) is one of the most preferred platinum-containing antineoplastic drugs. However, even in nontoxic plasma concentrations, it may cause kidney injury. To be able to increase its effective pharmacological dose, its side effects need to be regarded. Diet restriction (DR) has been demonstrated to improve cellular survival in a number of disorders. In this context, we investigated the role of DR in CP-induced nephrotoxicity (CPN). Besides alternate DR, animals were exposed to DR for 3 days prior or after CP treatment. Here, we observed that both 3 days of DR reverses the nephrotoxic effect of CP, which was associated with improved physiological outcomes, such as serum creatine, blood-urea nitrogen and urea. These treatments significantly increased phosphorylation of survival kinases PI3K/Akt and ERK-1/2 and decreased the level of stress kinase JNK were noted. In addition, the activation level of signal transduction mediator p38 MAPK phosphorylation was higher particularly in both three-day DR groups. Next, animals were fed with carbohydrate-, protein- or fat-enriched diets in the presence of CP. Results indicated that not only fasting but also dietary content itself may play a determinant role in the severity of CPN. Our data suggest that DR is a promising approach to reduce CPN by regulating metabolism and cell signaling pathways.

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“…Therefore, a stock solution of CDDP at 1 mg/mL was prepared in normal saline (0.9% NaCl w / v ). The availability of excess chloride ions prevents the isomerization of CDDP in saline and provides stable solutions that retain CDDP activity for at least 30 days [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

Iontosomes: Electroresponsive Liposomes for Topical Iontophoretic Delivery of Chemotherapeutics to the Buccal Mucosa

2021

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The targeted local delivery of anticancer therapeutics offers an alternative to systemic chemotherapy for oral cancers not amenable to surgical excision. However, epithelial barrier function can pose a challenge to their passive topical delivery. The charged, deformable liposomes—“iontosomes”—described here are able to overcome the buccal mucosal barrier via a combination of the electrical potential gradient imposed by iontophoresis and their shape-deforming characteristics. Two chemotherapeutic agents with very different physicochemical properties, cisplatin (CDDP) and docetaxel (DTX), were co-encapsulated in cationic iontosomes comprising 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and Lipoid-S75. The entrapment of CDDP was improved by formulating it in anionic reverse micelles of dipalmitoyl-sn-glycero-3-phospho-rac-glycerol sodium (DPPG) prior to loading in the iontosomes. Cryo-TEM imaging clearly demonstrated the iontosomes’ electroresponsive shape-deformable properties. The in vitro transport study using porcine mucosa indicated that iontosomes did not enter the mucosa without an external driving force. However, anodal iontophoresis resulted in significant amounts of co-encapsulated CDDP and DTX being deposited in the buccal mucosa; e.g., after current application for 10 min, the deposition of CDDP and DTX was 13.54 ± 1.78 and 10.75 ± 1.75 μg/cm2 cf. 0.20 ± 0.07 and 0.19 ± 0.09 μg/cm2 for the passive controls—i.e., 67.7- and 56.6-fold increases—without any noticeable increase in their transmucosal permeation. Confocal microscopy confirmed that the iontosomes penetrated the mucosa through the intercellular spaces and that the penetration depth could be controlled by varying the duration of current application. Overall, the results suggest that the combination of topical iontophoresis with a suitable nanocarrier system can be used to deliver multiple “physicochemically incompatible” chemotherapeutics selectively to oral cancers while decreasing the extent of systemic absorption and the associated risk of side effects.

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The physical and chemical stability of cisplatin (Teva) in concentrate and diluted in sodium chloride 0.9%

Cited by 21 publications

References 12 publications

Effect of different shielding conditions on the stability of Cisplatin

Effect of different shielding conditions on the stability of Cisplatin

Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice

Iontosomes: Electroresponsive Liposomes for Topical Iontophoretic Delivery of Chemotherapeutics to the Buccal Mucosa

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