Hierarchical hydrogel formation through micellization of amphiphilic block polypeptide in aqueous media

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Event Abstract Back to Event Hierarchical hydrogel formation through micellization of amphiphilic block polypeptide in aqueous media Monika Patel1 and Kazuaki Matsumura1 1 JAIST, School of Material Science, Japan Introduction: Synthetic polypeptides are unique biodegradable and biocompatible synthetic polymers with structures mimicking natural proteins. Their high potential for biomedical applications as functional materials arises from the amalgamation of a variety of amino acids, which allows diversity in terms of hydrophobicity/hydrophilicity and charge balances, as well as cause folding into specific secondary structures such as α-helices and β-sheets. Due to factors like high biocompatibility, minimal inflammatory responses, low toxicity and easy utilization to form amphiphilic structure these synthetic poly peptides have been used in various application of drug delivery, nano carriers, cell delivery and scaffold formation. Currently, several strategies combining polypeptide hydrogels with various therapeutic molecules (e.g., proteins, peptides, drugs and growth factors) are been investigated to improve the performance of the scaffolds. However, some of these strategies were unfavorable because of inability to encapsulate hydrophobic moieties in the hydrogels.Therefore, novel methods are needed to handle therapeutic molecules based on hydrogels. To address this issue we investigated formation of core shell polypeptide particles and their crosslinking to form hydrogels. Materials and Methods: N-carboxyanhydride (NCA) of the N-ε-Carbobenzoxy-L-lysine, L-Glutamic acid γ-benzyl ester and L-Phenylalanine (Watanabe chemicals) were synthesized using method adapted from literarture[1]. Single and diblock polypeptides are mainly prepared via ring opening polymerization (ROP) of amino acid N -carboxyanhydrides (NCAs) by using hexylamine as initiator. All polymerization reactions were performed in a dinitrogen filled glovebox using a reported protocol[2]. Further polymer was dissolved in trifluoroacetic acid and then HBr/acetic acid was added and stirred for deprotection before precipitating into excess ether. For micelle formation lyophilized diblock polymer was dissolved in distilled water. The core shell micelles were cross linked using glutaraldehyde at alkaline pH to yield a stable hydrogel. Results and Discussion: We successfully synthesized poly L lysine-b-poly L phenylalanine (PLL-b-PPA) and poly glutamic acid-b-poly phenylalanine (PGA-b-PPA) copolymers. The novel copolymer has been synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs). Polymerization conditions were optimized regarding block sequence and length. While the degree of polymerization of the PLL or PGA block length was varied from 100 to 200 and optimized around 100, PPA block lengths were varied from 5 to 20. The block copolymer with more the 5 DP of PPA block length were not readily soluble in water.The obtained block copolymers had a total degree of polymerization of 90−120 and dispersity indices between 1.2 and 1.3. Additionally, the block copolymers have been studied for micelle formation. The PLL200-b-PPA5 copolymer was found to yield micelles of 240.0 to 250.0 nm diameter and PGA200-b-PPA5 formed micelles with average diameter ranging between 200.0-220.0 nm as observed by DLS without drug, the average micelle size increases on drug encapsulation. PLL-b-PPA micelles were successfully linked using glutaraldehyde through the NH2 groups of the shell to yield a stable hydrogel. These drug loaded micelle cross linked hydrogels could be efficiently used for scaffold purpose. Conclusion: We successfully synthesised a core shell polypeptide micelles with different tail charges which can be efficiently cross linked by various chemical cross linker to yield a stable hydrogel matrix, which can further be used as drug encapsulating scaffold material.