Development of dissolving polymeric microneedles loaded with benzocaine nanocrystals as an effective intradermal drug...

The development of dissolving polymeric microneedles (DPMNs) loaded with drug nanocrystals is an innovative and minimally invasive approach for localized drug administration. In this work, benzocaine, a short-acting local anesthetic, was formulated into nanocrystals (BZ-NCs) and subsequently incorporated into polymeric microneedles. Several formulations of BZ-NCs were formulated via nanoprecipitation technique, utilizing ethanol as a solvent and varying aqueous concentrations of sodium lauryl sulfate (SLS), Polysorbate 80, or Poloxamer 188 as the antisolvent. The optimized formulation of BZ-NCs, which was developed utilizing 0.5% w/v SLS in the antisolvent phase, was assessed employing attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Moreover, the dissolution behavior of BZ-NCs was compared to that of plain benzocaine (BZ). DPMNs loaded with the optimized BZ-NCs formulation were prepared by mixing 25% w/w polyvinyl alcohol (PVA) and 35% w/w polyvinyl pyrrolidone (PVP) at ratios of 1:3, 1:2, or 1:1, respectively. The favorable formulation (1:1) was selected for further evaluation, including dissolution, accelerated stability, histological assessment and dermatokinetic analysis. The optimized nanocrystal formulation (BZ-NCs-3), exhibited a particle size of 291.12 ± 15.31 nm with polydispersity index and zeta potential of 0.261 ± 0.090 and -32.27 ± 1.04, respectively. ATR-FTIR confirmed the chemical structure integrity of benzocaine in BZ-NCs-3, while PXRD and DSC revealed its crystalline nature. Moreover, the dissolution of BZ-NCs-3 was significantly enhanced at pH 5.5 and 7.4 compared to BZ. The optimal microneedle formulation (BZNCs-MN3), having the highest PVA content, demonstrated effective penetration in excised human skin reaching a depth of 394.19 ± 20.402 µm, dissolved within 25 min and showed no significant changes in benzocaine content after accelerated storage. According to the dermatokinetic analysis, delayed and superior deposition of benzocaine in the epidermis and dermis were recorded following the application of BZNCs-MN3. This platform provides promise for improving local anesthesia with higher distribution of benzocaine in skin layers.