Vaginal delivery of carboplatin-loaded thermosensitive hydrogel to prevent local cervical cancer recurrence in mice

Abstract

Local tumor recurrence after cervical cancer surgery remains a clinical problem. Vaginal delivery of thermosensitive hydrogel may be suited to reduce tumor relapse rate with more efficacy and safety. A pilot study was carried out to evaluate the efficacy of carboplatin-loaded poloxamer hydrogel to prevent local recurrence of cervical cancer after surgery. In vivo vaginal retention evaluation of 27% poloxamer hydrogel in mice was proven to be a suitable vaginal drug delivery formulation due to its low gelation temperature. A mimic orthotopic cervical/vaginal cancer recurrence model after surgery was established by injecting murine cervical cancer cell line U14 into the vaginal submucosa to simulate the residual tumor cells infiltrated in the surgical site, followed by drug administration 24 h later to interfere with the formation/ recurrence of the tumor. By infusing fluorescein sodium-loaded hydrogel into the vagina of mice, a maximized accumulation of fluorescein sodium (Flu) in the vagina was achieved and few signals were observed in other organs. When used in the prevention of the cervical cancer formation/recurrence in mice, the carboplatin-loaded poloxamer hydrogel exhibited great efficacy and systemic safety. In conclusion, thermosensitive hydrogel presents a simple, practical approach for the local drug delivery via vagina against cervical cancer recurrence.

Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model

“…13 In general, HP hydrogel has been widely used for loading and delivering molecules to treat different diseases. 13,14 Recently, Wu et al developed and characterized an HP hydrogel containing acidic fibroblast growth factor (aFGF) for wound treatments and showed a clear therapeutic effect. 15 In addition, HP hydrogel loading nerve growth factor (NGF) enhanced the neuron regeneration in spinal cord injury.…”

“…16 We also found that HP hydrogel effectively increased the delivery of NGF via the blood-spinal cord barrier and showed a significant neuroprotective improvement in rats with spinal cord injury. 14 Therefore, a similar delivery system was applied in this study. We provided the first evidence that 17β-estradiol-loaded HP hydrogel effectively enhanced endometrial regeneration and the IUA recovery compared with 17β-estradiol only in cellular and animal models.…”

Hydrogels and Their Applications in Targeted Drug Delivery

“…Hydrogen peroxide trigger-mediated release of drugs could be achieved using hydrogels. This has been demonstrated previously with the use of ABC type triblock copolymer poly [(propylenesulfide)- b -( N , N -dimethylacrylamide)- b -( N -isopropylacrylamide)] [29,30] (PPS- b -PDMA- b -PNIPAM). A model hydrophobic drug, the dye red Nile was encapsulated in the hydrogel in order to demonstrate this.…”

Injectable Hydrogels for Localized Cancer Therapy

“…Its unique properties can be used as a drug carrier, which is injected into the body after being combined with a drug at a low temperature (Le et al, 2018). Forming a colloidal state with the help of body temperature makes it a drug sustained-release system, which simplifies not only medical treatment but also patients' suffering (Wang et al, 2015, 2016; Yang Y. et al, 2016). Main thermosensitive injectable hydrogels include chitosan/glycerophosphate (C/GP), hyaluronic acid (HA), PLGA based hydrogel, PEG-based hydrogel, PECE, and PECT (Guo et al, 2012; Klouda, 2015; Huang et al, 2016; Le et al, 2018; Sapino et al, 2019).…”