Principal Investigator:
Edith Mathiowitz, PhD, Professor
Department of Bio Med Molecular Pharmacology, Physiology & Biotechnology
Brown University
Providence, RI
Brief Description:
The use of micro- and nanoparticles for drug delivery is well known. Specifically, microsphere- and nanosphere-based polymeric drug delivery systems have great potential as oral delivery systems due to their ability to protect encapsulated active agents from the harsh gastrointestinal tract. Although significant effort has focused on developing effective delivery systems for clinical use, formidable obstacles exist in the development of effective nanoparticles for oral drug delivery such as achieving high enough levels of intestinal uptake to reach therapeutic concentrations of the encapsulated drug after administration.
To enhance uptake with bioadhesive properties, various materials are being explored for adherence to mucus membranes to thereby increase transit time in the gastrointestinal tract. However, salient limitations exist: premature drug release, loading difficulties with hydrophilic drugs, and physically entangled polymer chains with mucus impeding drug transit/translocation. Moreover, active control of drug release kinetics remains elusive with the occurrence of spontaneous ‘burst release’. Controlled release coatings have been employed to try to prevent the burst release phenomenon, but the complex uniform coating process, often using toxic organic solvents, is yet another challenge in manipulating a small nanoparticle/sphere.
The invention is a novel nanoparticle/sphere composition and method for improved oral drug delivery to significantly increase intestinal uptake of active agents/drugs that addresses the limitations of existing approaches as noted above. The innovation consists of a proprietary highly bioadhesive, polymeric nanoparticle formulation – a monodisperse plurality of nanoparticles formed from a polymeric material. An active agent may also be involved. These improved nanoparticles exhibit a relatively low contact angle with the mucin, and in spherical form, they have a higher binding ratio to the intestines compared with comparably sized nanospheres. There is an additional preparation method for multi-walled nanoparticles for use in controlled release of drugs/active agents. Overall, these flexible and versatile nanoparticles can load small or large biomolecules (proteins, nucleic acids), can be made from many different polymeric materials, biodegradable or non-, and may be combined with conventional pharmaceutically acceptable carriers.
Prophylactic, diagnostic and therapeutic applications exist for many diseases where oral delivery is desirable. The pharmaceutical drug delivery [device] market niche is relevant, for use in human and veterinary medicine, as well as the basic scientific R&D research tool market, with applications in drug discovery and development and nanomaterials.
Information:
US patent 8,673,359 is issued (03/18/2014)