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Controlled Release of Therapeutic Proteins
Published in Munmaya K. Mishra, Applications of Encapsulation and Controlled Release, 2019
Arruje Hameed, Tahir Farooq, Kanwal Rehman, Muhammad Sajid Hamid Akash
In such cases, the pH change has been found to be the controlling factor for implant formation and the release of therapeutic proteins. Generally, the pH-dependent water-soluble polymers form such polyanionic or polycationic systems. The solution form of polymers such as chitosan and alginate is converted into a gel with the change of pH after administration. Under acidic conditions, poly(methacrylic acid) is converted into gel form.77 Implants with controlled release of proteins have been developed using a layer-by-layer (LbL) coating approach.78,79 The implants were coated with polyelectrolyte using chondroitin (polyanion) and poly(β-aminoester)/poly2 (polycation) to load BMP-2.78 In in vitro studies at physiological pH, the BMP-2 was found to be released over a duration of 2 weeks. According to another study, the controlled delivery of BMP-264 was achieved using granules coated with hyaluronic acid/poly(l-lysine). Polyelectrolyte coating using poly(methacrylic acid) (polyanion) and poly-l-histidine (polycation) modified the surface of an anodized titanium implant. The pH-dependent release of protein was achieved due to this surface modification.80 The controlled delivery profile was studied using fluorescently labeled poly-l-lysine (15−30 kDa). For LbL-coated implants, the coating technique and molecular weight of poly(methacrylic acid) were found to affect the duration of release and burst release. The pH-dependent sustained release was observed at pH 7–8, while maximum release was detected at pH 5–6. bFGF and BMP-2 exhibited similar release profiles for 25 days from LbL-coated implants.81
N-isopropyl acrylamide) Interpenetrating Polymeric Networks
Published in Raphael M. Ottenbrite, Sung Wan Kim, Polymeric Drugs & Drug Delivery Systems, 2019
Jing Zhang, Nicholas A. Peppas
Poly(methacrylic acid) is an ionizable hydrophilic polymer. Crosslinked PMAA is insoluble but able to swell in water. Its swelling behavior is pH dependent due to the ionization/deionization of the carboxylic acid groups [8,9]. At low pH, usually pH < pKa, the COOH groups are not ionized. Thus, the PMAA network is in a collapsed state. At high pH values, the -COOH groups are ionized, and the charged COO- groups repel each other; this leads to PMAA swelling.
Design of polyelectrolyte core-shell and polyelectrolyte/non-polyelectrolyte Janus nanoparticles as drug nanocarriers
Published in Journal of Dispersion Science and Technology, 2018
Elham Dehghani, Mehdi Salami-Kalajahi, Hossein Roghani-Mamaqani, Tohid Barzgari-Mazgar, Shadi-Sadat Nasiri
Poly(methacrylic acid) is a weak anionic polyelectrolyte with carboxylic acid groups in its structure and its acid dissociation constant is about 4.8.[28] For pH values higher than pKa, PMAA chains are hydrophilic and negatively-charged due to the partial or complete deprotonation of carboxylic acid groups. In pH values less than pKa, the carboxylic acid groups are neutral and uncharged. In fact, the presence of negative charge on polymer chains at high pH values results in electrostatic repulsions between the chains and at low pH values, the chains are uncharged and their structure are collapsed.[29–30] Also, PHEMA has a slight dependence on pH due to delocalization of the electron density on the singly bonded oxygen to the electron-attracting carbonyl group at pH values higher than 13.[31] Conclusively, the pH of media is an important parameter to explain obtained morphologies. Table 2 shows the pH values prior to polymerization and the degree of ionization of PMAA polyelectrolyte seed particles and second domain in one together and rest feeding approaches.