Multidrug release based on microneedle arrays filled with pH-responsive PLGA hollow microspheres

Abstract This work presents an approach to codelivering transdermally two model drugs, Alexa 488 and Cy5, in sequence, based on a system of polyvinylpyrrolidone microneedles (PVP MNs) that contain pH-responsive poly( d , l -lactic-co-glycolic acid) hollow microspheres (PLGA HMs). The MN system provides the green fluorescence of Alexa 488 in PVP MNs, the red fluorescence of the DiI-labeled PLGA shell of HMs, and the cyan fluorescence of Cy5 in their aqueous core. Combined together, the prepared MN arrays support the localization of the HMs and the monitoring of the release profiles of model drugs within the skin tissues. The key component of this system is NaHCO3 , which can be easily incorporated into HMs. After HMs are treated with an acidic solution (simulating the skin pH environment), protons (H+ ) can rapidly diffuse through the free volume in the PLGA shells to react with NaHCO3 and form a large number of CO2 bubbles. This effect generates pressure inside the HMs and creates pores inside their PLGA shells, releasing the encapsulated Cy5. Test MNs were strong enough to be inserted into rat skin without breaking. The PVP MNs were significantly dissolved within minutes, and the first model drug Alexa 488, together with HMs, were successfully deposited into the tissues. Once in the acidic environment of the skin, the released HMs started to release Cy5 and continued to spread throughout the neighboring tissues, in a second step of the release of the drug. This approach can be used clinically to codeliver sequentially and transcutaneously a broad range of drugs.