Molecular Design and in Vitro Studies of Novel pH-Sensitive Hydrogels for the Oral Delivery of Calcitonin

Abstract

pH-sensitive hydrogels are suitable candidates for oral drug delivery of peptides due to their ability to respond to their environment. We have developed new hydrogels composed of poly(methacrylic acid) (PMAA) grafted with poly(ethylene glycol) (PEG) (P(MAA-g-EG)) which can be used as drug delivery carriers for salmon calcitonin. P(MAA-g-EG) hydrogels were prepared by free radical solution polymerization. The monomer mixture was diluted using a 50% w/w solution of ethanol and water. The percentage of monomer in solution was varied from 84% to 45% v/v. Swelling studies were conducted to investigate the effects of solvent content used during polymer preparation in the swelling behavior. The effects of dilution on the swelling behavior were not observed until the monomer mixture was diluted to approximately 50%. Salmon calcitonin was successfully incorporated and released in vitro from the system. Solutions of approximately 0.1 mg/mL of salmon calcitonin were used to load the protein into the gels at pH = 7 and constant ionic strength of 0.1 M. The loading efficiency was affected by the amount of solvent used during hydrogel preparation. In vitro release studies were performed at pH = 7 and 37 °C, while keeping an ionic strength of 0.1 M. The release behavior was found to be not very much affected by the amount of diluent used during polymer preparation. The transport mechanism was found to be relaxation controlled for all cases, and the diffusion coefficient was estimated using a heuristic Fickian/relaxational model.

Study of Water Adsorption in Poly(N-isopropylacrylamide) Thin Films Using Fluorescence Emission of 3-Hydroxyflavone Probes

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] One potential use is as coatings on drug eluting coronary stents, where the polymer can act both as a drug reservoir (e.g. providing local anti restenosis therapy) and as a biocompatibility modulator to improve device performance.…”

How Does the Initial Alignment of Mesogens Affect the Photoinduced Bending Behavior of Liquid‐Crystalline Elastomers?

“…[7] In addition, the bending of most polymer actuators, such as conducting polymers is driven by electrical energy; thus, these materials require wires to acquire electrical power. [3] On the other hand, elastomeric polymers, including gels and shape-memory polymers, can undergo mechanical actuation in response to various physical stimuli, such as pH, [8] solvent composition, [9] heat, [10][11][12] and light. [13,14] Light can be controlled remotely and rapidly as an external stimulus, so it is of great importance in developing simple, efficient, and compact elastomeric polymer actuators that can be driven by light.…”

Remote‐Controlled Hydrogel Depots for Time‐Scheduled Vaccination

“…[ 9 ] However, stimuli-sensing hydrogels developed to date have not reached clinical application due to trigger stimuli that are hardly compatible with human physiology or due to hydrogel building blocks likely to cause adverse reactions. For example, most stimuli-sensing hydrogels react to changes in temperature [ 10 ] or pH [ 11 ] beyond the physiological limits or are responsive to the administration of antigens, [ 12 , 13 ] ions [ 14 ] or metabolites [ 15 ] at concentrations hardly achievable in a therapeutic setting. One step in overcoming this stimulus incompatibility was the development of drug-sensing hydrogels that rely on clinically approved inducer molecules at pharmacologically relevant concentrations.…”