Compositions and formulations having one or more anti-freeze proteins for use with devices and systems that enable tissue cooling, such as cryotherapy applications, for alteration and reduction of adipose tissue are described. Embodiments of the technology are further directed to methods, compositions having one or more anti-freeze proteins and devices that protect non-targeted cells from freeze damage during dermatological and related aesthetic procedures requiring sustained exposure to cold temperatures. Further embodiments of the technology include systems for enhancing sustained and/or replenishing release of a freezing point depressant having one or more anti-freeze proteins to a treatment site prior to and during cooling applications.