Photocrosslinkable Triblock Copolymer Hydrogels for
Protein Encapsulation
Carson Smith, Lin Wu, Sitaraman Krishnan
Department of Chemical and Biomolecular Engineering, Clarkson University, Potsdam, NY 13676
Advances in biotechnology, such as the use of recombinant DNA technology, have led to an important
development in modern medicine, namely, the possibility of protein-based drugs. Protein-based drugs use
proteins to diagnose, prevent, or treat diseases, and are a promising alternative to conventional synthetic
drugs. Examples of protein-based drugs include erythropoietin, which is used for the treatment of anemia;
interferon, which acts against hepatitis B, a major cause of liver cancer; and tissue plasminogen activator
that prevent blood clotting for patients suffering from stroke. Another category of therapeutics that uses
biomolecules to treat diseases is the antisense therapy. Antisense therapy is based on engineered
inhibition of the synthesis of a diseases causing protein in a cell through binding of an oligonucleotide to
target messenger RNA. Diseases that display strong genetic underpinnings include cancer, Alzheimer’s
disease, Parkinson’s, and Tay-Sachs disease, to name a few. Oligonucleotide or RNA-based drugs are
known to shut off the production of a specific cancer-causing protein, called PLK1, and thereby lead to
the death of the cancer cell.
A major engineering challenge in the use of biomolecules as therapeutics is the delivery of these
molecules in the human body. The drug must be delivered into the blood stream and must reach the
targeted tissue without being destroyed by the body’s immune system. The protein-based drugs must also
not denature upon storage and delivery, otherwise they would be rendered useless. Block copolymer
hydrogels and block copolymer micelles are highly promising delivery vehicles for biomolecules.
The objective of our research is to develop novel photocrosslinkable hydrogels and study protein
encapsulation and release from these hydrogels. Photocrosslinking is an improved alternative to
conventional crosslinking using free radical chemistry or metal ions, as these chemical species can result
in a loss of functional activity of immobilized biomolecules. Our polymer consists of an ABA structure,
hence the triblock copolymer name, where the B block is poly (ethylene glycol) (PEG) and the A blocks
are each cinnamyl groups. Poly (ethylene glycol) is well known for its biocompatibility. The most
functional feature of this polymer is the photocrosslinking capability of the cinnamyl groups. When
exposed to UV radiation, these cinnamyl side groups bond with the cinnamyl side groups of adjacent
Clarkson University 2011
Chemical Engineering
Honors
Mentor: Sitaraman Krishnan, PhD
polymer chains (Figure 1). The crosslinking of the end-blocks creates a mesh-like structure which is
ultimately the mechanism for containing the protein-based drugs. The crosslinking reaction can be carried
out in the presence of the protein molecules, because of the benign nature of the light activated
crosslinking mechanism. The triblock copolymer was synthesized using Atom Transfer Radical
Polymerization (ATRP), which is an especially useful technique for our project given that it allows us to
synthesize symmetric triblock copolymers with a good control on molecular weight. The molecular
weight of the the central PEG block determines a critical characteristic: the density of the mesh structure.
Our crosslinked polymer is actually a hydrogel, which allows the mesh-structure to swell when immersed
in water. The degree of swelling allows for the calculation of the mesh-structure density using the
thermodynamic theories developed by Flory and Rehner. The protein release kinetics will be determined
by the interaction of protein with the hydrogel matrix and the mesh size of the hydrogel. The proteinhydrogel interaction is kept to a minimum using a protein-repellant PEG molecule as the matrix. Since we
have the capability of varying the molecular weight of our polymer chains, we can tailor the synthesis
technique to produce drug-delivery viable hydrogels when presented with a range of protein sizes. The
hydrogels under investigation can be used to encapsulate protein for protein-based drugs, and other
biomolecules such as oligonucleotides, for antisense therapy.
CH
CH
CH2
O
O
*
C
CH
CH2
PEG
CH2
O
CH
*
C
O
CH2
CH
CH
CH
CH
Light-induced crosslinking
CH2
O
C O
*
CH CH2
PEG
CH2CH
C
*
O
O
CH2
CH
CH
Figure 1. Photocrosslinkable triblock copolymer
Clarkson University 2011
Chemical Engineering
Honors
Mentor: Sitaraman Krishnan, PhD