Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia

Abstract

In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is based on injection of ethyl cellulose (EC)-ethanol to ablate the transformation zone around the os, the site most impacted by dysplasia. EC is a polymer that sequesters the ethanol within a prescribed volume when injected into tissue, and this is modulated by the injected volume and delivery parameters (needle gauge, bevel orientation, insertion rate, depth, and infusion rate). Salient injection-based delivery parameters were varied in excised swine cervices. The resulting injection distribution volume was imaged with a wide-field fluorescence imaging device or computed tomography. A 27G needle and insertion rate of 10 mm/s achieved the desired insertion depth in tissue. Orienting the needle bevel towards the outer edge of the cervix and keeping infusion volumes ≤ 500 µL minimized leakage into off-target tissue. These results guided development of a custom hand-held injector, which was used to locate and ablate the upper quadrant of a swine cervix in vivo with no adverse events or changes in host temperature or heart rate. After 24 h, a distinct region of necrosis was detected that covered a majority (> 75%) of the upper quadrant of the cervix, indicating four injections could effectively cover the full cervix. The work here informs follow up large animal in vivo studies, e.g. in swine, to further assess safety and efficacy of EC-ethanol ablation in the cervix.

Development of a 3D in vitro human-sized model of cervical dysplasia to evaluate the delivery of ethyl cellulose-ethanol injection

“…As previously reported, studies suggested that a concentration higher than 6% of EC-ethanol gave a localized injection with minimal leakage and highlighted the potential of ECethanol in precisely targeting diseased areas (Morhard et al, 2020). The complement analysis on cell viability and cell area gave a better understanding of cell response to the EC-ethanol treatment in comparison with previous studies that have reported only the effect of the volume distribution of EC-ethanol (Morhard et al, 2020;Mueller et al, 2021). These findings highlight the nuanced and comprehensive understanding that our model offers regarding cellular reactions to EC-ethanol, emphasizing its promise as an ideal model in which to study the relationship between EC-ethanol distribution and cellular response.…”

Development of a 3Din vitrohuman-sized model of cervical dysplasia to evaluate the delivery of ethyl cellulose-ethanol injection for the treatment of cervical dysplasia ablation

“…(33) The complement analysis on cell viability and cell area gave a better understanding of cell response to the EC-ethanol treatment in comparison with previous studies that have reported only the effect of the volume distribution of EC-ethanol. (33,34) These findings highlight the nuanced and comprehensive understanding that our model offers regarding cellular reactions to EC-ethanol, emphasizing its promise as an ideal model in which to study the relationship between EC-ethanol distribution and cellular response. Further studies with the inclusion of ECM components specific for cervical dysplasia could delve into the molecular mechanisms underpinning these observed effects, further advancing our understanding of how to best deliver EC-ethanol to treat cervical dysplasia.…”

Natural Polymeric Composites Derived from Animals, Plants, and Microbes for Vaccine Delivery and Adjuvant Applications: A Review

“…It works well as an immunosorbent or transport material since it is resistant to chemical reactions, pharmaceutically safe, and reasonably priced. According to the literature, a variety of cellulose derivatives, including ethyl cellulose (EC), methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropyl cellulose (HPMC), and ethyl hydroxy ethylcellulose (EHEC), have been used in vaccine delivery applications [ 85 , 86 , 87 , 88 ]. Moreover, vaccine carriers often employ microcrystalline cellulose (MCC).…”