Low gel strength agar, which is a polysaccharide-derived substance derived from red algae, is a huge attraction in drug delivery. In contrast to regular agar which has strong gelling action, low gel strength agar is a modified agar which is less gelling than normal agar and but softer and more malleable. Gel strength of low gel strength agar is between 200 and 300 g/cm2. This gel strength is extremely convenient for those use cases where you want the gel to be softer. This change is typically done by chemical or physical processes to reduce the gel strength and adapt it for particular application applications. These gels that are softer offer special benefits for drug delivery especially when it comes to applications where controlled and long-term release of therapy are required. The physical shape of agar can be manipulated, and researchers can build delivery systems that will not only protect sensitive drugs from degradation, but extend the release for as long as they would like. This capability is important to maximize drug performance, minimize dosing and maximize patient compliance.
Figure 1. Agar- and alginate-based composite hydrogel beads for oral drug delivery. (Zi-Chen Yin, et al.; 2018)
These are the major features of low gel strength agar in the delivery of drugs: excellent biocompatibility and biodegradability. Naturally produced, agar is also non-toxic and well-accepted by the body and does not pose any of the toxic side effects found in artificial polymers. This makes low gel strength agar perfect for delivery of any type of therapeutic substance from small molecule to macromolecule (proteins, peptides and nucleic acids). This biodegradability allows agar to be broken down and metabolized by the body so the delivery system doesn't have to be surgically excised following final release of the drug. This is especially helpful for implantable drug delivery systems, which can be adapted to degrade and release therapeutic payload over time with minimizing patient suffering and multiple interventions. It is also possible to use low gel strength agar to generate hydrogels, three-dimensional structures of polymer chains that can hold a lot of water. Those hydrogels can be modified to meet specific profiles for release of drugs by tweaking the agar concentration and composition. Addition of additional cross-linkers, for example, or mixing agar with other biopolymers can alter the gel's porosity and mechanical rigidity to regulate how quickly the drug migrates out of the matrix. Such personalisation is essential in tailoring drug delivery systems to the specific pharmacokinetic and pharmacodynamic profile of different therapeutics. What's more, low-gel strength agar hydrogels can be modified to respond to environmental conditions such as pH, temperature or enzymes. These "smart" hydrogels could release their drug payload according to physiological conditions — improving the precision and efficacy of drug delivery.
The first use of low gel strength agar in the delivery of drugs was for oral drug delivery. Oral route is the most popular delivery system because it is both convenient and patient-friendly. But the gut is also filled with obstacles to delivery, from acidic conditions, digestive enzymes and adsorption times. You can make low gel strength agar into enteric-coated tablets and capsules that keep the drug from breaking down in the stomach, and release it into the more neutral pH milieu of the intestines. Also, the mucoadhesive nature of agar-based hydrogels can extend the drug's dwell time in the gut to increase absorption and bioavailability. A second application of high gel strength agar is in transdermal drug delivery. Transdermal systems are an incision-free alternative to oral and injectable route that delivers the drug continuously through the skin into the bloodstream. You can use hydrogel agar to make transdermal patches that stick to the skin and deliver the drug in a controlled fashion. The hydrogels can be filled with all sorts of medication such as painkillers, hormones, or cardiovascular medicine. Low gel strength agar is comfortable to wear on the skin because it's pliable and soft, while being biocompatible. Moreover, we can also add penetration enhancers to the agar matrix, which can increase the drug's penetration through the skin, which is a therapeutic advantage. When it comes to injectable drug delivery, low gel strength agar has had tremendous success in making in-situ gelling platforms. These systems are at room temperature, but become gel-like once injected into the body, which creates a depot and slowly releases the drug. This method works well when delivering chemotherapy, for example, where an extended release of the drug can sustain therapeutic levels in the tumor microenvironment, which will enhance its anti-cancer effect while minimising systemic toxicity. Furthermore, the injectable gels can be customised to breakdown over a time-scale of choice, making it a customizable system for a variety of clinical conditions. Tissue engineering and regenerative medicine also use low gel strength agar. It can form biocompatible, biodegradable scaffolds and is a good material for supporting cell proliferation and tissue regeneration. For example, with agar hydrogels, growth factors, stem cells or other bioactive molecules can be delivered to the injury site to repair and regenerate tissues. The shape of the gel can be calibrated to the mechanical properties of the tissue to be grafted on, giving the right conditions for cell growth and differentiation. it's also possible to make the hydrogel matrix dispense bioactive molecules in a controlled way to improve the therapeutic performance of tissue engineering applications.
Alternate Names:
Soft Agar
Low Strength Agar
Weak Gel Agar
References:
1. Zi-Chen Yin, et al.; A pH-responsive composite hydrogel beads based on agar and alginate for oral drug delivery. Journal of Drug Delivery Science and Technology. 2018, Volume 43, Pages 12-18.
Characterization of physicochemical properties of carboxymethyl agar
Carbohydr Polym.
Authors: Cao M, Liu X, Luan J, Zhang X.
Abstract
A series of carboxymethyl agars (CMAs) with different degree of substitution (DS) were prepared, and their properties were determined and analyzed. The results showed that with the increase of DS, the dissolving temperature, the gelling temperature, the gel melting temperature, the gel strength, the gel hardness, the gel fracturability, and the solution apparent viscosity of CMA all decreased, except that its gel cohesiveness and gel springiness increased. The variation process of agar molecules in solution from coil to helix could be observed by measuring the optical rotation of the solution at such a low concentration, at which even the solution could not form a gel. The gel skeleton microstructures of both agar and CMA were of porous network structure, and the pore size of CMA became smaller and denser with the increase of its DS. After carboxymethylation, the agar hygroscopicity was improved, but its thermal stability was lowered.
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