Environment-sensitive hydrogels for drug delivery
TL;DR: Development of environmentally sensitive hydrogels with a wide array of desirable properties can be made is a formidable challenge, however, if the achievements of the past can be extrapolated into the future, it is highly likely that responsive hydrogelWith such properties can been made.
About: This article is published in Advanced Drug Delivery Reviews.The article was published on 2001-12-31. It has received 4216 citations till now. The article focuses on the topics: Self-healing hydrogels & Drug delivery.
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TL;DR: The synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks is reported, finding that these gels’ toughness is attributed to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping thenetwork of ionic crosslinks.
Abstract: Hydrogels with improved mechanical properties, made by combining polymer networks with ionic and covalent crosslinks, should expand the scope of applications, and may serve as model systems to explore mechanisms of deformation and energy dissipation. Hydrogels are used in flexible contact lenses, as scaffolds for tissue engineering and in drug delivery. Their poor mechanical properties have so far limited the scope of their applications, but new strong and stretchy materials reported here could take hydrogels into uncharted territories. The new system involves a double-network gel, with one network forming ionic crosslinks and the other forming covalent crosslinks. The fracture energy of these materials is very high: they can stretch to beyond 17 times their own length even when containing defects that usually initiate crack formation in hydrogels. The materials' toughness is attributed to crack bridging by the covalent network accompanied by energy dissipation through unzipping of the ionic crosslinks in the second network. Hydrogels are used as scaffolds for tissue engineering1, vehicles for drug delivery2, actuators for optics and fluidics3, and model extracellular matrices for biological studies4. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour5. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels6,7 have achieved stretches in the range 10–20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m−2 (ref. 8), as compared with ∼1,000 J m−2 for cartilage9 and ∼10,000 J m−2 for natural rubbers10. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties11,12,13,14,15,16,17,18; certain synthetic gels have reached fracture energies of 100–1,000 J m−2 (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ∼90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ∼9,000 J m−2. Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels’ toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.
3,856 citations
Cites background from "Environment-sensitive hydrogels for..."
...Hydrogels are used as scaffolds for tissue engineering [1], vehicles for drug delivery [2], actuators for optics and fluidics [3], and model extracellular matrices for biological studies [4]....
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TL;DR: The exciting successes in taming molecular-level movement thus far are outlined, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion are highlighted.
Abstract: The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.
2,301 citations
TL;DR: In this article, the authors focused on temperature and pH responsive polymer systems and additionally the other stimuli-based responsive polymers will be assessed, which is more helpful to design new approaches because the basic concepts and mechanisms are systematically connected.
2,233 citations
Cites background from "Environment-sensitive hydrogels for..."
...These responses of polymer systems are very useful in bio-related applications such as drug delivery [3,4,8–13], biotechnology [4,7,14], and chromatography [5,15,16]....
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...[8] Qiu Y, Park K....
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...1b), which has a LCST in the range of 25–35 8C, is an other popular temperature responsive polymer [8]....
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...Names coined for ‘stimuli-responsive’ polymers have been given as stimuli-sensitive [4], intelligent [5], smart [6,7], or environmentally sensitive polymers [8]....
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TL;DR: The newest developments in chitosan hydrogel preparation are investigated and the design parameters in the development of physically and chemically cross-linked hydrogels are defined.
2,034 citations
Patent•
10 Jun 2011
TL;DR: In this article, a surgical stapling device particularly suited for endoscopic procedures is described, which includes a handle assembly and an elongated body extending distally from the handle assembly.
Abstract: A surgical stapling device particularly suited for endoscopic procedures is described The device includes a handle assembly and an elongated body extending distally from the handle assembly The distal end of the elongated body is adapted to engage a disposable loading unit A control rod having a proximal end operatively connected to the handle assembly includes a distal end extending through the elongated body A control rod locking member is provided to prevent movement of the control rod until the disposable loading unit is fully secured to the elongated body of the stapling device
2,013 citations
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4,701 citations
TL;DR: The synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid) and aqueous solutions of these copolymers exhibit temperature-dependent reversible gel–sol transitions.
Abstract: Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems. Stimuli studied to date include chemical substances and changes in temperature, pH and electric field. Homopolymers or copolymers of N-isopropylacrylamide and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (known as poloxamers) are typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and non-biodegradable. Biodegradable polymers used for drug delivery to date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents. Such systems have the disadvantage that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue irritation and damage. Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid). Aqueous solutions of these copolymers exhibit temperature-dependent reversible gel-sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45 degrees C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for drugs.
1,930 citations
"Environment-sensitive hydrogels for..." refers background in this paper
...To add biodegradable capacity, the PPO segment of PEO–PPO– PEO block copolymers is often replaced by a biodegradable poly(L-lactic acid) segment [51–53]....
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TL;DR: An infinitesimal change in electric potential across a polyelectrolyte gel produces a discrete, reversible volume change, which can be several hundred times smaller than that of the swollen gel.
Abstract: An infinitesimal change in electric potential across a polyelectrolyte gel produces a discrete, reversible volume change. The volume of the collapsed gel can be several hundred times smaller than that of the swollen gel.
1,246 citations
"Environment-sensitive hydrogels for..." refers background in this paper
...These two simultaneous events lead to shrinking of the hydrogel at the anode side [100,101]....
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TL;DR: In this paper, the authors describe a chemomechanical system of this sort based on a synthetic polymer gel, which is anionic, and positively charged surfactant molecules can therefore bind to its surface, inducing local shrinkage by decreasing the difference in osmotic pressure between the gel interior and the solution outside.
Abstract: A SYSTEM capable of converting chemical energy to mechanical energy could serve as an actuator or an 'artificial muscle' in several applications. Here we describe a chemomechanical system of this sort based on a synthetic polymer gel. The gel network is anionic, and positively charged surfactant molecules can therefore bind to its surface, inducing local shrinkage by decreasing the difference in osmotic pressure between the gel interior and the solution outside. By using an electric field to direct surfactant binding selectively to one side of the gel, we can induce contraction and curvature of a strip of gel. Reversing the direction of the field causes contraction of the opposite side, and when the gel is suspended in solution from a ratchet mechanism, it can thereby be made to move with a worm-like motion at a velocity of up to 25 cm min−1.
1,173 citations
"Environment-sensitive hydrogels for..." refers background or methods in this paper
...Smart hydrogels have been used in diverse applications, such as in making artificial muscles [7–11], chemical valves [12], immobilization of enzymes and cells [13–21], and concentrating dilute solutions in bioseparation [22–27]....
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...Application of an oscillating electrode polarity could lead the hydrogel to quickly repeat its oscillatory motion, leading to a worm-like motion [10]....
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...If a cationic surfactant, such as n-dodecylpyridinium chloride, is added to the aqueous solution, the swelling occurs at the cathode side of the hydrogel [10]....
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TL;DR: It is shown that the hydrogel displays shape-memory behaviour, and that stepwise changes in antigen concentration can induce pulsatile permeation of a protein through the network.
Abstract: Stimuli-responsive hydrogels that undergo abrupt changes in volume in response to external stimuli such as pH, temperature and solvent composition have potential applications in biomedicine and the creation of 'intelligent' materials systems, for example as media for drug delivery, separation processes and protein immobilization. Hydrogels have been reported that respond to pH, temperature, electric fields and saccharides. For some biomedical applications it would be very useful to have a material whose swelling response was dictated by a specific protein. Here we report such a material, which swells reversibly in a buffer solution in response to a specific antigen. The hydrogel was prepared by grafting the antigen and corresponding antibody to the polymer network, so that binding between the two introduces crosslinks in the network. Competitive binding of the free antigen triggers a change in gel volume owing to breaking of these non-covalent crosslinks. In addition, we show that the hydrogel displays shape-memory behaviour, and that stepwise changes in antigen concentration can induce pulsatile permeation of a protein through the network.
1,064 citations
"Environment-sensitive hydrogels for..." refers background or methods in this paper
...Other stimuli include pressure [112], specific ions [113], thrombin [114–116] and antigen [117]....
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...A semi-interpenetrating network hydrogel was prepared by grafting an antigen and a corresponding antibody to different polymer networks [117]....
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...[117])....
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