Summary

The Schwendeman laboratories involves the use of mechanistic approaches to control the release of biomacromolecular drugs, vaccine antigens, and challenging small molecules (e.g., hydrophobic anticancer drugs) from biodegradable polymers.

Research Interests

  • Physical and chemical stability of microencapsulated bioactive agents. We examine the underlying molecular mechanisms responsible for the instability of substances, particularly proteins and other biomacromolecules, when encapsulated in the most commonly used material for controlled release, copolymers derived from lactic and glycolic acids (PLGA) and related biodegradable polymers.

  • Microencapsulation of biomacromolecules. We examine the underlying molecular mechanisms that govern microencapsulation, particularly for process-sensitive biomacromolecules. Through our mechanistic findings related to polymer/drug behavior in other projects, we have devised two new approaches for facile microencapsulation of biomacromolecular therapeutics with strong advantages over existing methods. These new methods will be published shortly and related patents are pending.

  • Surface modification of PLGA. We have devised patented facile methods of surface-modification of PLGA based on functional (FUN) emulsifiers, i.e., emulsifiers that impart biofunctional groups to the surface of the polymers. These physical methods obviate the need for performing chemistry to attach biofunctional groups on the surface of polymers. Due to their surface-active nature, FUN emulsifiers are easily surface-entrapped in PLGA, where a functional part of the molecule can then be utilized. Functional characteristics may include: rendering the polymer conjugatable, DNA condensable, or invisible to the body’s natural particle uptake system.

  • Mechanisms of controlled release. We continue to examine underlying mechanisms of initial burst release, and long-term controlled release of drugs, particularly biomacromolecules. We were among the first to recognize the importance of healing and other mechanisms responsible for large molecular drug release during the intitial burst. We have recently identified a role of healing during the erosion phase of release. We are currently expanding on these findings and evaluating their significance in vivo.

  • Long-acting Injectable depots. We apply our mechanistic studies toward development of novel injectable depots, particularly for biomacromolecular drugs.

  • Site-specific delivery of growth factors. We have created novel PLGA delivery systems, which are capable of delivery multiple drugs and growth factors with optimal stability and release characteristics from a single implant. Translating mechanistic studies with model proteins we have demonstrated that a single administration of long-acting PLGA-stabilized angiogenic growth factors (bFGF and/or VEGF) can rescue severely ischemic hindlimbs in SCID mice. Delivery of growth factors in tissue engineering is also of interest. Delivery of vaccine antigens. We continue to explore novel means of PLGA delivery of vaccine antigens. We are applying our stabilization, microencapsulation, and surface-mofication approaches for the delivery of prophylactic vaccine antigens and antigens used in contraceptive and cancer immunotherapies.

  • Site-specific delivery of chemotherapeutic and chemopreventive drugs. We continue to develop novel formulations for site-specific delivery of drugs for treatment and prevention of cancer, particularly oral cancer. We have extensive experience formulating PLGA delivery systems for over a dozen small molecules used in cancer.

Awards

  • 2002 Young Investigator Research Achievement Award, Controlled Release Society
  • 2010 Controlled Release Society Outstanding Consumer and Diversified Products Best Paper
  • 2015 AAPS Fellow
  • 2016 CRS College of Fellows Award