Interactions in dopamine and indole loaded thermosensitive hydrogels seen by high sensitivity microDSC. Implications for drug delivery

Abstract

Controlled and targeted drug delivery systems consist of a carrier matrix and one or more active ingredients. One of the roles of the matrix is to regulate the release of the drug. Uptake, release, differential scanning microcalorimetry (DSC) and powder X-ray diffraction (XRD) techniques were used to reveal the interactions governing the release of dopamine and indole from a thermoresponsive model polymer gel. The dopamine can be completely recovered from the loaded polymer matrix. The self-assembling affinity of the dopamine molecules reduces their interaction with the polymer, and the water molecules can form a uniform protecting water sheath. Thus neither the kinetics nor the temperature of the phase transition of the carrier matrix are influenced by the dopamine. The DSC results imply the formation of polymer and dopamine-rich domains above the phase transition. Indole, on the other hand, readily substitutes for the water molecules through the interaction between the C=O sites of the polymer and the NH groups of the drug. The loss of the protecting hydrophobic water and the decelerated fluctuation of the indole decorated polymer chains result in a much slower phase transition and a depleted phase transition temperature. The interaction between the carrier matrix and the indole results in a uniform distribution of the drug and after drying the indole is found in amorphous form. Dopamine, on the contrary, forms crystalline regions.

Interplay of the Influence of Crosslinker Content and Model Drugs on the Phase Transition of Thermoresponsive PNiPAM-BIS Microgels

“…The application of microgels for drug delivery purposes requires fundamental knowledge about interactions between polymeric structures and model drugs [ 39 , 40 ]. As medically relevant drugs often exhibit complex molecular structures, small aromatic model drugs are preferentially used to mimic the former [ 21 , 23 ].…”

“…Such aromatic additives shift the hydrophobic coil-to-globule transition of PNiPAM and poly( N , N -diethylacrylamide) (PDEAM) homopolymers to lower temperatures [ 41 ]. Concerning PNiPAM homopolymers and microgels, detailed studies involved phenol [ 23 , 32 , 40 ], hydroxybenzenes [ 41 ], benzaldehydes [ 21 , 41 ], and dopamine [ 23 , 40 ], as well as indol [ 40 ] and its dervatives [ 23 ]. For example, an indole ring as a component of various biologically active natural products was shown to interact with PNiPAM only above the LCST [ 23 ], while all aromatic additives reduce the phase transition temperature.…”