Hong, Minkyu Jason

Prenner, Elmar J.

PRISM: University of Calgary Digital Repository

University of CalgaryPRISM Repository https://prism.ucalgary.caConferences Students' Union Undergraduate Research Symposium2010Biophysical Investigation ofBiodegradable Nanoparticle Interactionswith Lung Surfactant ModelHong, Minkyu JasonHong, M. J. & Prenner, E. J. "Biophysical Investigation of Biodegradable NanoparticleInteractions with Lung Surfactant Model". 5th Annual Students' Union Undergraduate ResearchSymposium, November 25-26, 2010. University of Calgary, Calgary, AB.http://hdl.handle.net/1880/48817Downloaded from PRISM Repository, University of Calgary   1. Synthesize and characterize biodegradable nanoparticles and to select suitable sized nanoparticles for the study  2. Attain relevant data on nanoparticle-lipid interactions to be utilized in understanding their effects on lung surfactant  A key role of lung surfactant is maintaining the integrity of the lung during inhalation and exhalation by retaining high surface pressures.     Both controls (DPPC, DPPG) reach very high surface pressures This stability needs to be maintained for make pulmonary drug delivery feasible.   Gelatin nanoparticles do not reduce the surface pressure greatly and may be feasible materials for drugs carriers.    PBCA eliminates the stability of model lung surfactant and is thus  not a suitable for drug delivery purposes.    The study demonstrates that pulmonary drug delivery via nanoparticle is possible and proper biophysical assessment is an effective tool to screen suitable material.  Biophysical Investigation of Biodegradable Nanoparticle Interactions with Lung Surfactant Model  Minkyu Jason Hong and Elmar J. Prenner Department of Biological Sciences, University of Calgary, Calgary, Canada References Azarmi, S., Huang Y., Chen H., McQuarrie S., Roa W., Finlay W.F., Abrams D., Miller G.G. and R. Lonbenberg. (2006). Optimization of a two-step desolvation method for preparing gelatine nanoparticles and cell uptake studies in 143B osteosarcoma cancer cells. J Pharm Pharmaceut Science. 9: 124-132. Piknova B., Schram V. and S.B. Hall. (2002). Pulmonary surfactant: phase behaviour and function. Current Opinion in Structural Biology. 12: 487-494. Stuart D., Lobenberg R., Ku T., Azarmi S., Ely L., Roa W. and E.J. Prenner. (2006). Biophysical investigation of nanoparticle interactions with lung surfactant model systems. Journal of Biomedical Nanotechnology. 2: 245-252.   Drug delivery through the lungs is an attractive route of drug administration, due to the ease in treatment, lung specific disease targeting, and  bypassing of first-pass metabolism.   Here we investigated the interactions of gelatin and polybutylcyanoacrylate (PBCA) nanoparticles with model  lung surfactant systems using biophysical, in vitro methods.   Due to the biodegradability and biocompatibility of these materials, they are being considered as building blocks for nanoparticle based pulmonary drug delivery systems.  Introduction       Goals    Methods                     Gelatin nanoparticles weakly reduced the maximum surface-pressure of both DPPC and DPPG. PBCA NPs dramatically reduced model surfactant stability by inducing premature film collapse. Synthesis Gelatin nanoparticles were formulated through a two-step emulsion diffusion method. Polybutylcyanoacrylate (PBCA) nanoparticles were formulated through polymerization of the butylcyanoacrylate monomer.   Characterization  Dynamic light scattering (DLS) and Zetasizer were used to determine the size distribution of the nanoparticles which was 170.7 ± 2.3nm for gelatin and 165.3 ± 2.7nm for PBCA nanoparticles .  Model Lung Surfactant  Dipalmitoyl-phosphatidylcholine (DPPC) and   dipalmitoyl-phosphatidylglycerol (DPPG) are the main phospholipid components of lung surfactant and were selected as the model system.   Surface pressure-Area Isotherms  For the control experiments the phospholipids were spread on top of an aqueous subphase. For the subsequent experiments, nanoparticles were suspended in the aqueous subphase at a concentration of 1mg/ml, and the monolayer was spread on top before compression  to record changes in  surface pressure. Figure 5. Illustration of lipid monolayer compression and surface pressure-area  recording on Langmuir trough. Figure 6. Surface pressure-area isotherms of DPPC monolayers in the absence  and presence of both nanoparticle preparations.  Figure 7. Surface pressure-area isotherms of DPPG monolayers in the absence  and presence of both nanoparticle preparations. DPPC DPPG Control 58 mN/m 53mN/m Gelatin NP 53mN/m 45mN/m PBCA NP 12mN/m 17mN/m Figure 3. Diagram of alveolae and lung surfactant (Piknova et al., 2002) Figure 4. Gelatin nanoparticles of 260nm and 130nm. Figure 1.  Structural diagram  of DPPC Figure 2.  Structural diagram  of DPPG Zwitter-ionic  DPPC Anionic  DPPG  This work was performed in collaboration with Dr. Raimar Loebenberg form the Faculty of Pharmacy at the University of Alberta and supported by funds from the Alberta Cancer Board. Results           Discussion & Conclusion                 Acknowledgements

Biophysical Investigation of Biodegradable Nanoparticle Interactions with Lung Surfactant Model

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