Interest in stimuli-responsive polymers is steadily gaining increasing momentum especially in the fields of controlled and self-regulated drug delivery. Delivery systems based on these polymers are developed to closely resemble the normal physiological process of the diseased state ensuring optimum drug release according to the physiological need. Also termed 'environmental-sensitive' or 'smart', these polymers experience rapid changes in their microstructure from a hydrophilic to a hydrophobic state triggered by small changes in the environment. The changes are reversible; therefore, the polymer is capable of returning to its initial state as soon as the trigger is removed. Stimuli may occur internally (e.g. a change in pH in certain organs or diseased states, a change in temperature or the presence of specific enzymes or antigens). External stimuli include magnetic or electric fields, light, ultrasound, etc. This review will delve into the various internally and externally stimuli-responsive polymers and the drug delivery systems that exploit them.
Membrane technology is broadly applied in the medical field. The ability of membranous systems to effectively control the movement of chemical entities is pivotal to their significant potential for use in both drug delivery and surgical/medical applications. An alteration in the physical properties of a polymer in response to a change in environmental conditions is a behavior that can be utilized to prepare 'smart' drug delivery systems. Stimuli-responsive or 'smart' polymers are polymers that upon exposure to small changes in the environment undergo rapid changes in their microstructure. A stimulus, such as a change in pH or temperature, thus serves as a trigger for the release of drug from membranous drug delivery systems that are formulated from stimuli-responsive polymers. This article has sought to review the use of stimuli-responsive polymers that have found application in membranous drug delivery systems. Polymers responsive to pH and temperature have been extensively addressed in this review since they are considered the most important stimuli that may be exploited for use in drug delivery, and biomedical applications such as in tissue engineering. In addition, dual-responsive and glucose-responsive membranes have been also addressed as membranes responsive to diverse stimuli.
Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.
The purpose of this study was to formulate drug-loaded polyelectrolyte matrices constituting blends of pectin, chitosan (CHT) and hydrolyzed polyacrylamide (HPAAm) for controlling the premature solvation of the polymers and modulating drug release. The model drug employed was the highly water-soluble antihistamine, diphenhydramine HCl (DPH). Polyelectrolyte complex formation was validated by infrared spectroscopy. Matrices were characterized by textural profiling, porositometry and SEM. Drug release studies were performed under simulated gastrointestinal conditions using USP apparatus 3. FTIR spectra revealed distinctive peaks indicating the presence of -COO(-) symmetrical stretching (1,425-1,390 cm(-1)) and -NH (3) (+) deformation (1,535 cm(-1)) with evidence of electrostatic interaction between the cationic CHT and anionic HPAAm corroborated by molecular mechanics simulations of the complexes. Pectin-HPAAm matrices showed electrostatic attraction due to residual -NH(2) and -COO(-) groups of HPAAm and pectin, respectively. Textural profiling demonstrated that CHT-HPAAm matrices were most resilient at 6.1% and pectin-CHT-HPAAm matrices were the least (3.9%). Matrix hardness and deformation energy followed similar behavior. Pectin-CHT-HPAAm and CHT-HPAAm matrices produced type IV isotherms with H3 hysteresis and mesopores (22.46 nm) while pectin-HPAAm matrices were atypical with hysteresis at a low P/P(0) and pore sizes of 5.15 nm and a large surface area. At t (2 h), no DPH was released from CHT-HPAAm matrices, whereas 28.2% and 82.2% was released from pectin-HPAAm and pectin-CHT-HPAAm matrices, respectively. At t (4 h), complete DPH release was achieved from pectin-CHT-HPAAm matrices in contrast to only 35% from CHT-HPAAm matrices. This revealed the release-modulating capability of each matrix signifying their applicability in controlled oral drug delivery applications.
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