Stabilization and Release Effects of Pluronic F127 in Protein Drug Delivery

In modern times, protein drugs have had an ever-increasing ability to efficiently combat disease in the human body, and delivery of polypeptide agents, whether insulin or interferons, to biological targets has thus become a task of great importance to doctors and patients alike. For this reason, it is the goal of many medical researchers to preserve the bioactivity of specific protein drugs and find methods for their delivery. Non-ionic surfactants are an attractive vehicle for protein drugs. The polypeptide stabilizing abilities of surfactants have been verified by past experimentation; the addition of surfactants (such as Tweens and Pluronics) has been shown to increase the ability of polypeptides to remain bioactive. Keeping polypeptides in their active or native state is often a difficult task. The thermodynamic fragility of proteins makes it possible for them to physically denature due to changes in temperature or pH, or simply as a result of agitation of their medium. Lyophilization, or freeze drying, is another process which can severely damage a protein’s ability to function. Even proteins in ideal conditions are subject to forces of degradation. In the process of folding from primary to tertiary structure, a polypeptide passes through many intermediate states which have hydrophobic residues exposed to the aqueous environment. If intermediate structures encounter each other, they can form protein aggregates, whereby the polymers exclude their hydrophobic residues from the surroundings by conglomerating together and thus minimizing the potential energy of their system more effectively than the native state. Aggregates are mainly non-bioactive states which remain in equilibrium concentration in any protein solution, and are one of the largest obstacles to maintenance of protein drug bioactivity. There are many theories as to how non-ionic surfactants are able to help maintain a protein’s native state. One hypothesis is that the surfactant, as an amphipathic (simultaneously hydrophilic and hydrophobic) compound, can compete with the enzyme for a denaturing surface, for surfactants have been shown to specifically halt surface-induced denaturation when added to a protein solution. Other investigations suggest that the surfactant can help decrease the potential energy of a surfactant-adsorbed protein through weak hydrophobic bonding, thus lowering the Gibbs free energy of the system and increasing the native conformation’s stability. Pluronic F127 is one such surfactant with an additional property in aqueous solution: at or above room temperature, a solution of F127 will convert from its liquid state to that of a nonfluid hydrogel. Such a characteristic immediately suits it to protein drug Stabilization and Release Effects of Pluronic F127 in Protein Drug Delivery