Effect of temperature on the release rate of biomolecules from thermally reversible hydrogels

doi:10.1016/S0376-7388(00)80377-4

Journal of Membrane Science

Volume 33, Issue 2, September 1987, Pages 191-200

https://doi.org/10.1016/S0376-7388(00)80377-4 Get rights and content

Abstract

Poly(N-isopropylacrylamide) hydrogels exhibit a lower critical solution temperature (LCST) and as a result these hydrogels shrink and deswell in aqueous solutions when the temperature is raised through their LCST. This phenomenon is reversible and the gels expand and reswell upon cooling below the LCST. We have investigated the application of these hydrogels in controlled delivery of biologically and industrially important substances. The delivery rate can be greatly accelerated by a relatively small temperature increase through the LCST. We have investigated the swelling of these gels as a function of gel composition and temperature; we have also studied the effect of temperature on the release kinetics of vitamin B 12 from the gel matrix. Biomedical, biotechnological, and industrial applications of such gels are suggested which involve the delivery or removal of drugs, toxins, solutes or solvents.

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Fabrication of core–shell PLGA/PLA–pNIPAM nanocomposites for improved entrapment and release kinetics of antihypertensive drugs
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Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) are two commonly applied biodegradable polymers for the preparation of nanocomposites used in drug-delivery systems. However, these polymers lack desirable attributes such as resistance to aggregation during long-term storage due to lyophilisation. To improve their efficacy, in this work, PLA and PLGA were encapsulated within a shell of poly(N-isopropylacrylamide) (pNIPAM) using a single emulsion technique followed by an aqueous free radical precipitation polymerisation process, yielding core–shell PLA/PLGA–pNIPAM nanocomposites. The nanocomposites were characterised using zeta potential, dynamic light scattering, and transmission electron microscopy analyses and were further applied as a delivery system for ramipril, an antihypertensive drug. The drug-loaded PLGA–pNIPAM core–shell nanoparticles exhibited a higher drug content (91%) and entrapment efficiency (78%) than their PLA counterparts. An in vitro release study of the formulations at pH 7.3 in phosphate-buffered saline indicated that PLGA was more efficient than PLA with a sustained release of 86% of ramipril from the polymer matrix within 24 h. Furthermore, to determine the release kinetics, the data were fitted to Korsmeyer–Peppas and Higuchi models; the release of ramipril from the polymer matrix followed zero-order rate kinetics and an anomalous (non-Fickian) diffusion mechanism.
Swelling of poly(N-isopropylacrylamide) P(NIPA)-based hydrogels with bacterial-synthesized prodigiosin for localized cancer drug delivery
2016, Materials Science and Engineering C
Citation Excerpt :
The uptake, storage and delivery of cancer drugs can be facilitated by the use of gels [15–17]. These include: environmentally-sensitive gels that can respond to local stimuli, such as temperature, pH, electric fields and solvent composition [18–21]. The swelling and controlled release of cancer drugs [22,23] from such gels can, therefore, provide the basis for the design of implantable biomedical systems for the localized treatment of cancer.
We present the results of swelling experiments on poly(N-isopropylacrylamide) P(NIPA)-based hydrogels. The swelling characteristics of P(NIPA)-based homo-polymer and P(NIPA)-based co-polymers with Acrylamide (AM) and Butyl Methacrylate (BMA), were studied using weight gain experiments. The swelling due to the uptake of biosynthesized cancer drug, prodigiosin (PG), was compared to swelling in controlled environments (distilled water (DW), paclitaxel™ (PT) and bromophenol blue (BB)). PG was synthesized with Serratia marcescens (SM) subsp. marcescens bacteria. The mechanisms of drug diffusion and swelling of P(NIPA)-based hydrogels are also elucidated along with characterizing the heterogeneous porous structure of the P(NIPA)-based hydrogels. High Performance Liquefied Chromatography (HPLC) analysis revealed the purity of the biosynthesized prodigiosin to be 92.8%. PG was then absorbed by P(NIPA)-based hydrogels at temperatures between 28–48 °C. This is a temperature range that might be encountered during the implantation of biomedical devices for localized cancer treatment via drug delivery and hyperthermia. The results obtained are shown to provide insights for the design of implantable biomedical devices for the localized treatment of breast cancer.
Prodigiosin release from an implantable biomedical device: Kinetics of localized cancer drug release
2014, Materials Science and Engineering C
Citation Excerpt :
The increasing incidence of cancer [1] has stimulated research on the development of novel implantable devices for the localized treatment of cancer [2–5].
This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10^− 12 m²/s and 4.8 × 10^− 6 m²/s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices.
Low temperature plasma vapor treatment of thermo-sensitive poly(N-isopropylacrylamide) and its application
2013, Applied Surface Science
Citation Excerpt :
PBT is a hydrophobic material that frequently needs to be treated before application [17]. In this study of PNIPAAm treated and untreated glass slides and PS petri dish, with considering of the temperature of the human body is close to the LCST, these results are valuable for further application on the thermo-sensitive textile materials [18–22]. In the study of PNIPAAm was deposited onto PBT melt-blown nonwoven, it was found that the water permeability can be significantly modified by changing of the temperature at around LCST.
In this study, the novel methods of depositing poly(N-isopropylacrylamide) (PNIPAAm) coatings on the surface of glass slides and PS petri dish by plasma polymerization are provided. PNIPAAm can be obtained by plasma polymerization of N-isopropylacrylamide by using the self-made equipment of plasma vapor treatment. The samples were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and water contact angle. SEM analysis has revealed that the poly(N-isopropylacrylamide) (PNIPAAm) coatings were formed on the surface of the smooth glass slides. Further evaluation by using XPS, it has shown the presence of PNIPAAm. The wettability can be significantly modified by changing of the temperatures at above and below of the lower critical solution temperature (LCST) from the data of the contact angle test. These results have advantage for further application on the thermo-sensitive textile materials. On the deposition of PNIPAAm onto Polybutylene Terephthalate (PBT) melt-blown nonwovens in atmospheric pressure plasma, water permeability was significantly modified at around LCST. Due to the LCST is close to the temperature of human body, it has advantage on application of PBT melt-blown nonwovens.
Investigation of swellable poly (N-isopropylacrylamide) based hydrogels for drug delivery
2011, Materials Science and Engineering C
Citation Excerpt :
Besides specific polymer matrix designs for hydrogel drug delivery, efforts have been made to develop mathematical models for the control of the drug release mechanisms in drug delivery systems [20–22]. Fick's first and second laws have been used to describe diffusion with constant (or time dependent) diffusion coefficients in diffusion-controlled drug release systems [1,23]. However, it is usually difficult to obtain analytical solutions when drug release occurs from complex geometries.
The thermo-sensitive properties of poly (N-isopropylacrylamide) (PNIPA) hydrogels are modified by the addition of hydrophilic acrylamide comonomers and an interpenetrating network of sodium alginate for drug delivery applications near 37 °C. A mathematical model is presented to describe the mass transport kinetics during the hydrogel drug delivery process, which is accompanied by a volume change during phase transition. In this model, the transport in the polymer matrix is described by Fick's second law in cylindrical coordinates, with concentration dependent diffusion coefficients. The moving boundary problems caused by the polymer matrix swelling are also solved by numerical simulation. The models show that the Trypan blue release from the modified PNIPA-based hydrogels is strongly concentration dependent. The sodium alginate component is also shown to effectively facilitate the diffusion process. The results from the simulation are in good agreement with the measurements of diffusion and swelling observed from in vitro experiments. The implications of this work are also discussed for practical drug delivery systems.
Effects of temperature on diffusion from PNIPA-based gels in a BioMEMS device for localized chemotherapy and hyperthermia
2011, Materials Science and Engineering C
This paper presents the results of an experimental study of the effects of temperature on the diffusion from poly(N-isopropylacrylamide) (PNIPA)-based gels with hydrophilic (acrylamide) or hydrophobic (butyl methacrylate) co-monomers. The elutions of rhodamine dye and cancer drug, paclitaxel^™ are studied over a range of temperatures in which localized chemotherapy can be combined with hyperthermia (37–45 °C). Dye and drug release from the gels is shown to be well described by monolithic and membrane diffusion models. The current work introduces a multi-modal device that can potentially kill cancer cells by chemotherapy and hyperthermia. A clear advantage over prior devices is the ability to combine these two therapeutic interventions in one device. The implications of the results are discussed for the development of thermosensitive drug eluting Bio-Micro-Electro-Mechanical Systems (BioMEMS) devices that can treat cancer locally via the combined effects of chemotherapy and hyperthermia.

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^☆: Paper presented at the ACS Regional Meeting held in Portland, Oregon, June 1986

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Effect of temperature on the release rate of biomolecules from thermally reversible hydrogels☆

Abstract

Polymer

J. Controlled Release

Thermally reversible hydrogels. II. Delivery and selective removal of substances from aqueous solutions

J. Controlled Release

Solution properties of poly(N-isopropylacrylamide)

J. Macromol. Sci.-Chem.

Preparation of films exhibiting a balanced temperature dependence to permeation by aqueous solutions — A study of lower consolute behavior

J. Polym. Sci.

Aqueous solutions of poly(N-isopropylacrylamide)

J. Appl. Polym. Sci.

Solution properties of poly (N-isopropylacrylamide)

Makromol. Chem.

Gels

Sci. Amer.

Osmotic deswelling of gels by polymer solutions

Macromolecules