(340at) Development of Nanoemulsion-Loaded Hydrogels for Advanced Pharmaceutical Formulations

In past decades, tons of new active pharmaceutical ingredients (APIs) have been synthesized to save people’s lives from many diseases. However, advances in drug development have mainly focused on the discovery of new APIs, and there has been less innovation in the formulation steps. Current formulation processes generally require many inefficient steps, and the resulting drug products can still lack flexible controls over their release behaviors. Throughout my PhD, I have utilized two promising building blocks, functional nanoemulsions and hydrogels, to develop versatile drug products and efficient pharmaceutical formulation processes.

Design and use of a thermogelling methylcellulose nanoemulsion to formulate nanocrystalline oral dosage forms

Nanocrystalline formulations are an attractive route to increase the solubility of hydrophobic APIs, but typically require abrasive mechanical milling and several processing steps to create an oral dosage form. Using the dual amphiphilic and thermoresponsive properties of methylcellulose (MC), I developed a new thermogelling nanoemulsion and a facile thermal dripping method for efficient formulation of composite particles with the MC matrix embedded with precisely controlled API nanocrystals. Moreover, a fast and tunable release performance is achieved with the combination of a fast-eroding MC matrix and fast-dissolving API nanocrystals. Using the versatile thermal processing approach, the thermogelling nanoemulsion is easily formulated into a wide variety of dosage forms (nanoparticle suspension, drug tablet, and oral thin film) in a manner that avoids nanomilling. Overall, the proposed thermogelling nanoemulsion platform not only broadens the applications of thermoresponsive nanoemulsions but also shows great promise for more efficient formulation of oral drug products with high quality and tunable fast release.

Nanoemulsion-loaded capsules for controlled delivery of lipophilic active ingredients

Nanoemulsions have become ideal candidates for loading hydrophobic active ingredients and enhancing their bioavailability in the pharmaceutical, food, and cosmetic industries. However, the lack of versatile carrier platforms for nanoemulsions hinders advanced control over their release behavior. In this work, I developed a method to encapsulate nanoemulsions in alginate capsules for the controlled delivery of lipophilic active ingredients. Functional nanoemulsions loaded with active ingredients and calcium ions are first prepared, followed by encapsulation inside alginate shells. The intrinsically high viscosity of the nanoemulsions ensures the formation of spherical capsules and high encapsulation efficiency during the synthesis. A quantitative analysis of the release profiles shows that the capsule systems possess a tunable, delayed-burst release. The encapsulation methodology is generalized to other active ingredients, oil phases, nanodroplet sizes, and chemically crosslinked inner hydrogel cores. Overall, the capsule systems provide promising platforms for various functional nanoemulsion formulations.

Publications

• L-H. Chen, P. S. Doyle*, “Design and use of a thermogelling methylcellulose nanoemulsion to formulate nanocrystalline oral dosage forms.” Advanced Materials (2021): 2008618. Featured in MIT news and 12 other news items.
• L-H. Chen, L.-C. Cheng, P. S. Doyle*, “Nanoemulsion-loaded capsules for controlled delivery of lipophilic active ingredients.” Advanced Science (2020): 2001677. Featured in MIT news.

Research Interests

Nanoemulsions, Hydrogels, Controlled Release, Crystallization, Microfluidics, Membrane Separations