A self-assembled co-hydrogel system with sol-gel two-phase coexistence and mucoadhesive properties was developed based on the combined properties of fluoroalkyl double-ended poly(ethylene glycol) (Rf-PEG-Rf) and poly(acrylic acid) (PAA), respectively. We have synthesized an Rf-PEG-g-PAA (where g denotes grafted) copolymer and integrated it into the Rf-PEG-Rf physically cross-linked micellar network to form a co-hydrogel system. Tensile strengths between the co-hydrogel surfaces and two different sets of mucosal surfaces were acquired. One mucosal surface was made of porcine stomach mucin Type II, while the other one is a pig small intestine. The experimental results show that the largest maximum detachment stresses (MDSs) were obtained when the Rf-PEG-g-PAA’s weight percent in the dehydrated polymer mixture is ~15%. Tensile experiments also found that MDSs are greater in acidic conditions (pH = 4–5) (123.3 g/cm2 for the artificial mucus, and 43.0 g/cm2 for pig small intestine) and basic conditions (pH = 10.6) (126.9 g/cm2, and 44.6 g.cm2, respectively) than in neutral pH (45.4 g/cm2, and 30.7 g.cm2, respectively). Results of the rheological analyses using shear strain amplitude sweep and frequency sweep reveal that the Rf-PEG-g-PAA was physically integrated into the Rf-PEG-Rf micellar network, and the co-hydrogels remain physically cross-linked in three-dimensional micellar networks with long-term physical dispersion stability. Therefore, the co-hydrogel system is promising for drug delivery applications on mucosal surfaces.
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Multi-responsive polypeptide hydrogels derived from N-carboxyanhydride terpolymerizations for delivery of nonsteroidal anti-inflammatory drugs
A polypeptide-based hydrogel system, when prepared from a diblock polymer with a ternary copolypeptide as one block, exhibited thermo-, mechano- and enzyme-responsive properties, which enabled the encapsulation of naproxen (Npx) during the sol–gel transition and its release in the gel state. Statistical terpolymerizations of l -alanine (Ala), glycine (Gly) and l -isoleucine (Ile) NCAs at a 1 : 1 : 1 feed ratio initiated by monomethoxy monoamino-terminated poly(ethylene glycol) afforded a series of methoxy poly(ethylene glycol)- block -poly( l -alanine- co -glycine- co - l -isoleucine) (mPEG- b -P(A-G-I)) block polymers. β-Sheets were the dominant secondary structures within the polypeptide segments, which facilitated a heat-induced sol-to-gel transition, resulting from the supramolecular assembly of β-sheets into nanofibrils. Deconstruction of the three-dimensional networks by mechanical force (sonication) triggered the reverse gel-to-sol transition. Certain enzymes could accelerate the breakdown of the hydrogel, as determined by in vitro gel weight loss profiles. The hydrogels were able to encapsulate and release Npx over 6 days, demonstrating the potential application of these polypeptide hydrogels as an injectable local delivery system for small molecule drugs.
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- NSF-PAR ID:
- 10173086
- Date Published:
- Journal Name:
- Organic & Biomolecular Chemistry
- Volume:
- 15
- Issue:
- 24
- ISSN:
- 1477-0520
- Page Range / eLocation ID:
- 5145 to 5154
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C7OB00931C
