Pulmonary hypertension is a progressive and severe condition with severe, and often fatal, consequences. Despite remarkable therapeutic advancements over the last thirty years, mortality rates remain as high as 40%. Current therapies largely target the major regulatory pathways involved in vascular tone. These therapies are associated with considerable limitations such as, a short half-life, formulary hurdles, low bioavailability, instability in acidic environments, and non-specific distribution. Similarly, smoke inhalation injury increases the mortality of burn victims by 20% compared to burn injury alone and current therapies remains supportive, which include mechanical ventilation, antibiotics, fluid resuscitation, and routine intensive care of patients. There is a lack of treatment targeted to the injured lung tissue in both of these groups of patients. Due to the limitations of the therapeutic approaches for targeted treatment of the damaged pulmonary tissue in these patients, there are often unwanted systemic side effects. This highlights the need for novel therapies to effectively treat pulmonary hypertension and smoke inhalation injury for improving patient outcomes.
Researchers in the Department of Surgery have developed a targeted nanoparticle drug delivery system that uses peptide amphiphiles (PA). These PA spontaneously self-assemble into nanofibers when placed in an aqueous environment and are customizable to target a tissue of interest for delivery of a therapeutic agent. A targeting sequence is attached to a PA backbone and through co-assembly with other non-targeted PAs, the PAs can encapsulate drugs in their hydrophobic core. This allows for delivery of drugs that would otherwise display poor oral bioavailability and allow for delivery directly to a tissue of interest, such as injured lung tissue. Synthesis, purification, characterization, and specific targeting by nanofibers to injured lung tissue has been demonstrated in both pulmonary hypertension and smoke inhalation injury animal models. The nanofibers present a drug delivery system that is biodegradable, biocompatible, easily delivered by intravenous administration, customizable, and targeted for improved treatment of pulmonary hypertension and smoke inhalation injury patients.
• Targeted drug delivery approach, which provides maximal therapeutic effect to the injured pulmonary tissue without systemic adverse effects.
• Encapsulation of hydrophobic drugs improve therapeutic bioavailability.
• Customized targeting to a tissue of interest allows for wide applicability of the system to other diseases.
In addition to treating pulmonary hypertension and smoke inhalation injury patients, the targeted nanofibers can be used for treating other pulmonary conditions such as, cystic fibrosis and chronic obstructive pulmonary disease.
- ACE-targeted Peptide Amphiphile Nanofibers for Localized Treatment of Pulmonary Hypertension Marulanda1, A. Mercel1, M. Gambarian1, D. C. Gillis1, K. Sun1, M. Karver2, N. D. Tsihlis1, S. E. McLean1, M. R. Kibbe1 1University Of North Carolina At Chapel Hill,Department Of Surgery,Chapel Hill, NC, USA 2Northwestern University,Simpson Querrey Institute,Chicago, IL, USA.
- Development of a Targeted Nanofiber to Treat Smoke Inhalation Injury Sun1, B. Dandurand1, M. Karver2, N. Tsihlis1, R. Maile1, B. Cairns1, M. R. Kibbe1 2Northwestern University,Chicago, IL, USA 1University Of North Carolina At Chapel Hill,Chapel Hill, NC, USA.