The use of biodegradable poly([beta]-amino ester) and poly([beta]-amino amide) microspheres as an experimental therapeutic delivery vector for selective cancer cell targeting

by Shipton, Matthew K.

Shipton, Matthew K. The Use of Biodegradable Poly(?-amino ester) and Poly(?-amino amide) Microspheres as an Experimental Therapeutic Delivery Vector for Selective Cancer Cell Targeting. (Advised by Daniel L. Feldheim) The design, synthesis, and use of new biodegradable polymers for drug delivery applications is an area of ever increasing interest. Polymeric drug delivery systems have several advantages compared to conventional drug delivery methods such as liposomes and antibodies. Since liposomes are spherical vessels made of phosphorolipids, they are tiny particles which can be taken up by the macrophages. Antibodies, meanwhile, have the disadvantage that most receptor sites on tumor cells are also present on healthy cells. Several of these advantages include localized delivery, improved drug efficiency, and drug protection of certain medications which may degrade rapidly when inside the body. Poly(?-amino esters) and Poly(?-amino amides) are ideal polymers for the encapsulation, delivery, and release of various therapeutic agents to cancer cells, which have an acidic extra cellular pH level, near 6.81. Poly(?-amino esters) and Poly(?-amino amides) are specifically designed to degrade by hydrolysis of the ester and amide bonds respectively, in the polymer backbone. Microspheres of Poly(?-amino ester) and Poly(?-amino amide) are formed via a double emulsion process using Rhodamine B-Isothiocyanate (RBITC) labeled Bovine Serum Albumin (BSA) as the encapsulate. The fluorescence intensity of the RBITC-BSA released from the polymer sphere was measured as a way of testing polymer backbone hydrolysis. The polymer microspheres were placed into different solutions of varying pH ranges. The pH range extended from pH 5.5 to pH 7.4. The hydrolyzed polymer byproducts were removed and the resulting supernatant tested for fluorescence intensity. The results showed polymer hydrolysis and release of labeled BSA at pH 6.8 and lower. . The Use of Biodegradable Poly(?-amino ester) and Poly(?-amino amide) Microspheres as an Experimental Therapeutic Delivery Vector for Selective Cancer Cell Targeting. By Matthew K. Shipton A Thesis Submitted to the Graduate Facility of North Carolina State University in Partial Fulfillment of the Requirements for the Degree of Masters of Science Department of Chemistry Raleigh, North Carolina August 12, 2004 Approved by: _____________________________________________________________________________ Dr. Daniel L. Feldheim, Chair of Advisory Committee ________________________________________________ Dr. Edmond F. Bowden _____________________________________________ Dr. David A. Shultz I dedicate this Thesis to my loving friends and family, It has been a long bumpy road with many ups and downs, But through it all, you were always there. ii Biography Matthew K. Shipton was born February 17, 1979 in Sharon Pennsylvania. He is the son of Larry and Dr. Sharon Shipton. Matthew spent all of his childhood in the small Western Pennsylvania town of Grove City. Matthew received his primary education from Highland Park Elementary School and Grove City Middle School. He attended Grove City Area Senior High School, earning both academic and athletic scholarships before graduating in 1997. In the fall of 1997 Matthew enrolled at Youngstown State University earning the Division I-AA National Championship in football with his team in 1997. He was also a member of the 1999 Division I-AA National Finalist team. Matthew graduated from Youngstown State in 2001 earning a Bachelor of Science in Chemistry and minor degrees in the area of Philosophy, Mathematics, and Economics. Through his hard work and dedication Matthew earned a Teaching Assistantship to attend North Carolina State University. He moved to Raleigh in August of 2001. In December of 2001 Matthew began his graduate research working under the advisement of Daniel L. Feldheim. Through his hard laboratory work and his problem solving ability he was promoted to Research Assistant after his first year under Dr. Feldheim. Matthew received his Master of Science in Chemistry degree in December of 2004. iii