Poly[(R)-3-hydroxybutyrate] (PHB) is a naturally occurring biopolymer synthesized by numerous bacterial species through the fermentation of sugar or lipids. This biopolymer has emerged as a material of interest in the field of drug delivery due to its remarkable biocompatibility, biodegradability, and the potential for being produced from renewable resources. As the pharmaceutical industry increasingly prioritizes sustainability, PHB offers a promising alternative to traditional synthetic polymers, which are often derived from petrochemical sources and can pose environmental hazards. This introduction explores the characteristics that make PHB suitable for drug delivery, its advantages over other materials, and the current research trends focused on enhancing its application in this critical area. PHB's biocompatibility is one of its most significant advantages for drug delivery systems. When implanted in the human body, PHB degrades into D-3-hydroxybutyric acid, a compound naturally present in human metabolism. This degradation pathway minimizes the risk of adverse inflammatory responses, unlike many synthetic polymers that can trigger significant immune reactions. This characteristic is particularly valuable in the development of drug delivery vehicles designed for long-term implantation, such as those used in the delivery of anticancer drugs, where prolonged exposure to the delivery system is necessary. Additionally, the degradation rate of PHB can be fine-tuned by modifying its molecular weight or by blending it with other polymers, allowing for the controlled release of drugs over a specified period. This ability to engineer the degradation rate is crucial for maintaining therapeutic drug levels in the body, thus enhancing the efficacy of the treatment.
Figure 1. Chemical structure of poly-(3-hydroxybutyrate), poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly-(3-hydroxybutyrateco-3-hydroxyhexanoate). (Peña C, et al. 2014)
The versatility of PHB extends beyond its biocompatibility. Its physical properties, including high crystallinity and melting temperature, provide structural integrity to drug delivery systems. These properties ensure that the encapsulated drugs remain stable and protected until they are released at the target site. PHB can be processed into various forms such as nanoparticles, microspheres, films, and scaffolds, each offering unique advantages for different types of drug delivery. For example, PHB nanoparticles can be used for targeted drug delivery, allowing for the direct administration of drugs to diseased cells, thus minimizing side effects and improving treatment outcomes. Microspheres made from PHB are ideal for the sustained release of drugs, which is beneficial for treating chronic conditions requiring consistent medication levels over extended periods. Moreover, PHB's compatibility with various drug molecules is another significant benefit. It can encapsulate a wide range of drugs, from small molecules to larger biologics like proteins and nucleic acids. This broad compatibility enhances its utility in developing multifaceted drug delivery systems that can address complex therapeutic needs. For instance, in cancer therapy, PHB-based systems can be engineered to co-deliver chemotherapeutic agents and gene therapies, potentially improving treatment efficacy and reducing the likelihood of drug resistance. Additionally, the surface properties of PHB can be modified to improve drug loading efficiency and release profiles, making it a highly adaptable material for various medical applications.
Current research on PHB in drug delivery is focused on optimizing its properties to further enhance its performance. Scientists are exploring the incorporation of other biodegradable polymers or copolymers to create PHB-based composites with improved mechanical properties and tailored degradation rates. These composites can provide even more precise control over drug release profiles, which is essential for achieving optimal therapeutic outcomes. Additionally, there is ongoing research into surface modification techniques to improve the interaction between PHB-based delivery systems and biological tissues. By enhancing these interactions, researchers aim to improve the targeting and uptake of drugs by specific cells or tissues, thereby increasing the efficacy of treatments while minimizing side effects. Another exciting area of research involves the use of PHB in combination with advanced drug delivery technologies. For example, PHB is being studied for its potential use in the development of stimuli-responsive drug delivery systems. These systems can release their drug payload in response to specific physiological triggers, such as changes in pH, temperature, or the presence of specific enzymes. This targeted release mechanism can significantly improve the precision of drug delivery, ensuring that drugs are released only at the site of action, thereby enhancing their effectiveness and reducing systemic side effects. The development of such sophisticated delivery systems holds great promise for advancing personalized medicine, where treatments are tailored to the specific needs of individual patients.
Alternate Names:
PHB
Poly(3-hydroxybutanoate)
(R)-3-Hydroxybutyrate homopolymer
References:
1. Peña C, et al. Biotechnological strategies to improve production of microbial poly-(3-hydroxybutyrate): a review of recent research work. Microb Biotechnol. 2014, 7(4):278-93.
2. Mota C, et al. Additive manufacturing of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] scaffolds for engineered bone development. J Tissue Eng Regen Med. 2017, 11(1):175-186.
Cationic Poly([R]-3-hydroxybutyrate) Copolymers as Antimicrobial Agents
Macromol Biosci
Authors: Liow SS, Chee PL, Owh C, Zhang K, Zhou Y, Gao F, Lakshminarayanan R, Loh XJ.
Abstract
Poly([R]-3-hydroxybutyrate) (PHB), a natural biodegradable polyester, has attracted much attention as a new biomaterial because of its sustainability and good biocompatibility. In this study, it is discovered that PHB can be conveniently functionalized to obtain a number of platform chain architectures that may provide a wide range of functional copolymers. In a transesterification reaction, linear (di-hydroxylated) and star shaped (tri- and tetra-hydroxylated) PHB oligomers are synthesized, followed by copolymerization with 2-(dimethylamino)ethyl methacrylate and quaternization with benzyl bromide to afford antimicrobial properties. The antimicrobial activities of the quaternary salts against clinically relevant pathogens on the interactions with outer and cytoplasmic membranes, lethal mechanisms, multipassage resistance, and synergy effect with antibiotics are investigated. Cationic PHB copolymers show effectiveness as antimicrobial agents, with minimum inhibitory concentration values 0.24-0.65 μm (or μmol dm-3 ) (or 32-128 μg mL-1 ) against Gram-positive and Gram-negative bacteria. Modifying the copolymer architectures into star shapes results in enhanced effectiveness to disrupt the membrane integrity. Synergistic effects are attained for all the quaternized PHB derivatives when they are used together with tobramycin. Multipassage resistance does not occur in both the linear and star derivatives against Gram-negative bacteria after 20 passages.
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