(M0930-12-68) Ethyl Cellulose Coated Polymeric Microneedles for Sampling of Drugs and Biomarkers from the Tissues

Purpose: The objective was to explore the potential use of polymer-coated polymeric (PCP) microneedles for sampling analytes from the dermal tissue. Ethylcellulose was explored as a potential polymer for coating the microneedles. The secondary objective was to fabricate a more efficient PCP microneedle by embedding an adsorbent in the microneedles and evaluate their performance.

Methods: PDMS silicon molds were used to cast the microneedles. PVP K-30 (20% w/v) was dissolved in deionized water to prepare the casting solution. Carboxen was added to the casting solution. Fabricated carboxen loaded microneedles were coated with ethyl cellulose solution (4% prepared in toluene) by Dip and spin technique (Figure 1). Adsorbent loaded polymer coated polymeric microneedles were fabricated with an objective to enable the PCP microneedles to recover significantly higher amounts of analytes. The feasibility of using PCP microneedles for sampling analytes was investigated using model molecules like nicotine, sodium fluorescein, and prednisolone phosphate. PCP microneedles were applied for different durations of time intervals (15, 30, 45, and 60 minutes). After predetermined time intervals, the coated microneedles were retracted and analyzed for the drug content of analyte present in them. To assess the validity of the PCP microneedle approach of sampling analytes, the skin was equilibrated with different concentration solutions of the three APIs to generate different amounts of drug levels. Following which, the PCP microneedles were applied on the tissue and the analytes were sampled by placing them in contact with the tissue for 15 min and 45 min. Transepidermal water loss (TEWL) of the porcine skin, used for sampling analytes, was recorded.

Results: The coating formulation was optimal at 4% ethylcellulose solution. The model molecules studied here are of different physicochemical properties (sodium fluorescein (log P= 0.1), prednisolone sodium phosphate (log P =1.15) and nicotine (log P=1.17). In addition, the model molecules also represent molecules of high (sodium fluorescein 80%), moderate (prednisolone phosphate 60%) and low protein (nicotine 5%) binding category. TEWL of the porcine skin increased from 7.2±1.7 g/m².h to 15.23±1.55 g/m².h when the skin was treated with coated microneedles. The significant increase in TEWL indicates the perturbation of the physical barrier of the skin by the ethylcellulose coated microneedles. All three analytes were recovered in significant amounts from the skin. The amount of analyte extracted from the skin depends on the duration of insertion of the coated needles in the tissue (Figure 2). The content recovered from the tissue was in the following order nicotine˃ prednisolone phosphate˃ sodium fluorescein. There was a linear relationship between the amounts of analytes recovered at different concentrations versus the amount of analyte in the skin tissue (figure 3). The PCP microneedles embedded with adsorbent was subjected to sampling of the three analytes and the duration of sampling was 15 minutes. The incorporation of adsorbent did not improve the recovery of hydrophilic molecule sodium fluorescein. However, the recovery of lipophilic molecules prednisolone phosphate and nicotine were enhanced by six (3.15±0.58 to 20.92±3.14) and three-fold (10.4±2.5 to 3.44±7.5 ug) respectively. The results clearly demonstrated that the adsorbent embedded PCP microneedles could be one of the approaches to enhance the amounts of analytes sampled from the tissues, particularly the lipophilic molecules.

Conclusion: The analytes of different physiochemical nature could be sampled from the tissue using a PVP microneedle array and the amount of analyte sampled was proportional to the concentration of analyte in the tissue. The PCP microneedles were modified by incorporating adsorbent beads into the core microneedles which enhanced the extent of recovery of lipophilic analytes.

Acknowledgements: The author is thankful to the efforts of Dr.Norman Richardson (Incrux LLC) for capturing the carboxen loaded PCP Microneedles


Figure 1: Carboxen loaded PCP microneedle


Figure 2: Amount of analytes sampled from the skin using PCP microneedles after different duration of exposure


Figure 3: a) Amount of sodium fluorescein sampled at different equilibrium dermal levels b) Amount of prednisolone phosphate sampled at different equilibrium dermal levels c) Amount of nicotine sampled at different equilibrium dermal levels