ABSTRACT
Monoclonal antibodies (mAbs) provide unchallenged specificity compared to small molecules, representing a
growing market of 150+ billion dollars. Due to their structural complexity and poor stability, however, they remain
difficult to formulate at high concentrations, making intravenous (IV) delivery of mAbs the “gold standard”. IV
injections present major drawbacks, such as patient discomfort, long injection times, and high medical costs
associated with in-hospital administration. Subcutaneous (SC) delivery is a convenient route of administration
for large molecules, as it allows for rapid injections (seconds), requires minimal skills (self-injection), and allows
for systemic delivery. It remains an open challenge to reformulate mAbs to a SC form. Most mAbs requires large
dosage to be effective (>300 mg), and SC administration volumes are constrained to only 1-2 ml, hundreds of
times smaller than typical IV formulations
SC injections using hydrogel microparticles (HMP) offer a promising method for encapsulating and delivering
protein-based drugs. The composition, size, and mechanical properties of HMPs can be widely tuned to facilitate
their injection through needles for subcutaneous delivery. Alginate-based MP are becoming increasingly popular
due to their rheological properties and high biocompatibility. Additionally, the anionic nature of alginate enables
electrostatic entrapment of cationic proteins independently of the hydrogel porosity, making it a candidate for
hydrogel-based antibody formulations. However, current manufacturing technologies are limited to low
concentration of polymer (<5%), and low cargo loading, typically below 30 mg/ml for antibodies, resulting in
inadequate mechanical and therapeutic properties.
Through the support of this Small Business Innovation Research (SBIR) Phase I project, we aim at improving
clinical care of millions of patients by reformulating IV-delivered mAbs to a SC form, meaning patients could
administer their life saving drugs with reduced pain and discomfort, at a fraction of the cost.
We plan to leverage Acoustophoretic Printing (AP) to generate alginate MP to stabilize highly concentrated mAbs
formulation. This platform technology enables microparticle generation under modest shear forces without the
need for a hydrophobic carrier fluid, thereby protecting the valuable cargo and minimizing contamination. The
technology features: high bio-compatibility with no oil or surfactant required, making this technology particularly
suitable for large proteins; high concentrations of cargo (>100mg/ml), including alginate (>10%); low particle size
variation (coefficient of variation of 1-3%) reducing costly sieving steps, consistency in cargo encapsulation and
delivery - hence significantly improving Good Manufacturing Practices - even at extreme loading.
This project aims to: (1) Manufacture mAbs loaded hydrogel-based microparticles for SC delivery and
characterize them in-vitro, including encapsulation efficiency, release profile, and injectability. (2) Conduct In vivo
study to investigate safety, bioavailability, and bioactivity of the MP-based formulations in murine models.
