Biopolymer based nanomaterials in drug delivery systems: A review

Drug delivery systems, including liposomes, gels, prodrugs, and so forth, are used to enhance the tissue benefit of a pharmaceutical drug or conventional substance at a specific diseased site with little toxicological impact. Nanotechnology can be a rapidly developing multidisciplinary science that enables the production of polymers at the manometer scale for different medical applications. The use of biopolymers in drug delivery systems provides compatibility, biodegradability and low immunogenicity biologically. Large‐scale and smaller‐than‐expected medication particles can be delivered using biopolymers such as silk fibroins, collagen, gelatine, and others that are easily formed into suspensions. These drug carrier systems are functional at improving drug delivery and can be used in intranasal, transdermal, dental, and ocular delivery systems. This study discusses the latest developments in drug delivery methods based on nanomaterials, mainly using biopolymers like proteins and polysaccharides.

Targeted delivery of drug molecules to diseased sites is a great challenge in pharmaceutical and biomedical sciences. Fabrication of drug delivery systems (DDS) to target and/or diagnose sick cells is an effective means to achieve good therapeutic results along with a minimal toxicological impact on healthy cells. Biopolymers are becoming an important class of materials owing to their biodegradability, good compatibility, non-toxicity, non-immunogenicity, and long blood circulation time and high drug loading ratio for both macros as well as micro-sized drug molecules. This review summarizes the recent trends in biopolymer-based DDS, forecasting their broad future clinical applications. Cellulose chitosan, starch, silk fibroins, collagen, albumin, gelatin, alginate, agar, proteins and peptides have shown potential applications in DDS. A range of synthetic techniques have been reported to design the DDS and are discussed in the current study which is being successfully employed in ocular, dental, transdermal and intranasal delivery systems. Different formulations of DDS are also overviewed in this review article along with synthesis techniques employed for designing the DDS. The possibility of these biopolymer applications points to a new route for creating unique DDS with enhanced therapeutic qualities for scaling up creative formulations up to the clinical level.

Concepts and System Design for the Rate-Controlled Drug Delivery Fundamentals of Rate-Controlled Drug Delivery Oral Drug Delivery and Delivery Systems Mucosal Drug Delivery: Potential Routes for Noninvasive Systemic Administration Nasal Drug Delivery and Delivery Systems Ocular Drug Delivery and Delivery Systems Transdermal Drug Delivery and Delivery Systems Parenteral Drug Delivery and Delivery Systems Vaginal Drug Delivery and Delivery Systems Intrauterine Drug Delivery and Delivery Systems Systemic Delivery of Peptide-Based Pharmaceuticals Regulatory Considerations in Controlled Drug Delivery

Nanomaterial-based drug delivery systems (DDSs) increase the efficacy of various therapeutics, and shear stress has been shown to be a robust modulator of payload release. In the past few decades, a deeper understanding has been gained of the effects of flow in the body and its alteration in pathological microenvironments. More recently, shear-responsive nanomaterial DDSs have been developed. Studies on this subject mainly from the last decade are reviewed here, focusing on innovations of the material design and mechanisms of the shear response. The two most popular shear-controlled drug carriers distinguished by different release mechanisms, that is, shear-deformable nanoparticles (NPs) and shear-dissociated NP aggregates (NPAs), are surveyed. The influence of material structures on their properties such as drug loading, circulation time, and shear sensitivity are discussed. The drug development stages, therapeutic effects, limitations, and potential of these DDSs are further inspected. The reviewed research emphasizes the advantages and significance of nanomaterial-based shear-sensitive DDSs in the field of targeted drug delivery. It is also believed that efforts to rationally design nanomaterial DDSs responsive to shear may prompt a new class of diagnostics and therapeutics for signaling and rectifying pathological flows in the body.

Silk is a natural polymer with unique physicochemical and mechanical properties which makes it a desirable biomaterial for biomedical and pharmaceutical applications. Silk fibroin (SF) has been widely used for preparation of drug delivery systems due to its biocompatibility, controllable degradability and tunable drug release properties. SF-based drug delivery systems can encapsulate and stabilize various small molecule drugs as well as large biological drugs such as proteins and DNA to enhance their shelf lives and control the release to enhance their circulation time in the blood and thus the duration of action. Understanding the properties of SF and the potential ways of manipulating its structure to modify its physicochemical and mechanical properties allows for preparation of modulated drug delivery systems with desirable efficacies. This review will discuss the properties of SF material and summarize the recent advances of SF-based drug and gene delivery systems. Furthermore, conjugation of the SF to other biomolecules or polymers for tissue-specific drug delivery will also be discussed.

Silk Fibroin (SF), a natural source material obtained from Bombyx mori, has been widely enlisted as biomaterial having outstanding mechanical properties. SF has been reported as one of the propitious bio-polymers for various drug delivery systems, as well as drug delivery vehicle. This review is a summary of comprehensive applications of silk fibroin in various drug delivery systems, and also to present the current opportunities and requirements by furnishing a definitive assessment on silk fibroin as a polymer. SF has been reported as one of the propitious bio-polymers for various drug delivery systems, as well as drug delivery vehicle. SF is inestimable owing to its non-toxic and non-antigenic character, except for the firmness formation whilst being stored at lower temperature. Unlike other polymeric biomaterials, SF is regenerated in aqueous systems in defined temperature, pressure and pH, which is one of its major advantages in formulation. SF nanoparticles are also used to deliver proteins and peptides. Recently, SF has been used to deliver anti-cancer agents like paclitaxel, doxorubicin, floxuridine, and methotrexate, and including the natural product curcumin, has shown to elicit significant biological activity when compared to their conventional form. Interestingly, SF has shown to be a promising biomaterial for implantables and injectable drug delivery applications. In the present review, we have summarized the physical and chemical properties, biocompatibility and non-immunogenic characters of SF and its applications in various drug delivery systems.

Around 100 years ago, Paul Ehrlich postulated the “magic bullet”, a personalized and tailored drug that can hit the affected tissue like a bullet from a gun. Since then on a lot of research has been conducted to develop such “magic bullets”. To deliver a drug to the target location, usually a carrier/vehicle is needed (drug delivery system). Conventional ways to administer drugs are by tablets or parenterals, whereas the latter often suffers from high plasma concentration for a short time period, followed by a more or less fast decrease of the plasma concentration. Depending on the elimination constant, repeated drug administration can lead either to a diminished effect if the active ingredient is fast eliminated, or to side effects if the active ingredient cumulates. To control the release, local drug release might be considered with the advantage that systematic side effects can be reduced. As a result, local drug delivery systems gain more and more interest with the challenge to achieve a sustained release without impacting the surrounding healthy tissue. In order to achieve this controlled drug delivery and an optimal therapeutic effect, a lot of research has been carried out for targeted delivery with a controlled release rate. However, a drug delivery system has to meet several requirements, e.g. mechanical stability, controllable structure and degradation. Due to its extraordinary properties (e.g. mechanical strength, biocompatibility, biodegradability into non-toxic products, FDA-approved), silk fibroin (SF) has been in the focus of research since a long time, especially in terms of sustained release drug delivery systems. One of the major advantages of SF compared to other biomaterials is that it can be assembled into a variety of matrices (e.g. particles, foams, gels, electrospun mats) [1, 2]. The objective of the first study was to characterize silk fibroin in more detail. The focus was set on different purification processes of SF in order to efficiently remove sericin and a method to detect residual sericin was established. This is important to ensure biocompatibility since the combination of sericin and silk fibroin can cause allergic reactions. The degumming process significantly affected SF integrity, particularly mechanical strength and molecular weight distribution. These factors are crucial for the preparation of drug delivery systems, since they can influence the degradation rate of the drug delivery system and as a result, the release rate of the drug. The second study aimed to investigate the release behaviour of differently charged macromolecular drugs from SF films. Since biologicals and nucleic acids (respectively nucleic acid/polymer complexes) are becoming an emerging field, the importance to understand the release behaviour of these macromolecular, charged compounds is growing. Therefore, differently charged, high molecular weight dextran derivatives, used as model drugs, were encapsulated into SF films and their release behaviour was studied. Additionally, the effect of SF purification process, with focus on degumming time, on drug release was elucidated. The release rate was found to be highly dependent on matrix properties, controllable via the purification process. In the third part, silk fibroin films were chemically modified via copper (I)-catalyzed alkyne-azide cycloaddition (CuAAC) to further control drug release. The already existing, extraordinary features of silk fibroin can be enlarged by chemical modification, extending their range of applications. By varying the modification degree, the release was controlled, aiming a more pronounced sustained release, and additionally, the surface properties with regard to hydrophilicity were tuned.

Microfluidic devices were fabricated from silk fibroin using an aqueous molding process adapted from soft lithography. The process results in mechanically robust, patent devices with macroscopic fluidic connections. Hepatocytes were seeded in the device and perfused for up to five days during which they exhibited liver-specific functions equivalent to that observed for standard tissue culture substrates. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2007/c2487_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Nanotechnology has revolutionized the field of medicine, particularly in the development of novel drug delivery systems. Nanomaterial-based drug delivery systems offer several advantages over traditional methods, including enhanced therapeutic efficacy, improved bioavailability, targeted delivery, and reduced side effects. This review provides an overview of the applications and recent advancements in nanomaterial-based drug delivery systems. The first section of this review focuses on the different types of nanomaterials used in drug delivery, including liposomes, polymeric nanoparticles, dendrimers, carbon-based nanomaterials, and metallic nanoparticles. Each nanomaterial has unique physicochemical properties that can be tailored to optimize drug encapsulation, release, and targeting. The second section highlights the importance of nanoscale characterization techniques in evaluating the properties and performance of nanomaterial-based drug delivery systems. Characterization techniques such as dynamic light scattering, transmission electron microscopy, atomic force microscopy, and spectroscopic methods enable researchers to analyze particle size, morphology, surface charge, drug loading, and release kinetics. The third section discusses the application of nanomaterial-based drug delivery systems in various therapeutic areas, including cancer treatment, cardiovascular diseases, infectious diseases, and neurological disorders. These systems can be engineered to selectively accumulate at the target site, enhancing drug efficacy and minimizing off-target effects. The fourth section explores recent advancements in nanomaterial-based drug delivery systems, including stimulus-responsive and multifunctional nanocarriers. Stimuli-responsive systems can release drugs in response to specific triggers, such as changes in pH, temperature, or enzymatic activity, leading to site-specific drug release. Multifunctional nanocarriers combine drug delivery with diagnostic imaging, allowing real-time monitoring of drug distribution and therapeutic response. The final section addresses the challenges and future perspectives in the field of nanomaterial-based drug delivery systems. Challenges include regulatory considerations, toxicity concerns, scalability, and clinical translation. Future directions involve the development of personalized nanomedicine, combination therapy approaches, and integration with other emerging technologies, such as artificial intelligence and gene editing. In conclusion, nanomaterial-based drug delivery systems have shown great potential for improving the efficacy and safety of therapeutic interventions. The advancements in nanotechnology offer exciting opportunities for the development of next-generation drug delivery platforms, opening new avenues for personalized medicine and targeted therapies. However, further research and collaborations are required to address the challenges associated with clinical translation and ensure the safe and effective implementation of these systems in clinical practice.

Nanotechnology has revolutionized the field of medicine, particularly in the development of novel drug delivery systems. Nanomaterial-based drug delivery systems offer several advantages over traditional methods, including enhanced therapeutic efficacy, improved bioavailability, targeted delivery, and reduced side effects. This review provides an overview of the applications and recent advancements in nanomaterial-based drug delivery systems. The first section of this review focuses on the different types of nanomaterials used in drug delivery, including liposomes, polymeric nanoparticles, dendrimers, carbon-based nanomaterials, and metallic nanoparticles. Each nanomaterial has unique physicochemical properties that can be tailored to optimize drug encapsulation, release, and targeting. The second section highlights the importance of nanoscale characterization techniques in evaluating the properties and performance of nanomaterial-based drug delivery systems. Characterization techniques such as dynamic light scattering, transmission electron microscopy, atomic force microscopy, and spectroscopic methods enable researchers to analyze particle size, morphology, surface charge, drug loading, and release kinetics. The third section discusses the application of nanomaterial-based drug delivery systems in various therapeutic areas, including cancer treatment, cardiovascular diseases, infectious diseases, and neurological disorders. These systems can be engineered to selectively accumulate at the target site, enhancing drug efficacy and minimizing off-target effects. The fourth section explores recent advancements in nanomaterial-based drug delivery systems, including stimulus-responsive and multifunctional nanocarriers. Stimuli-responsive systems can release drugs in response to specific triggers, such as changes in pH, temperature, or enzymatic activity, leading to site-specific drug release. Multifunctional nanocarriers combine drug delivery with diagnostic imaging, allowing real-time monitoring of drug distribution and therapeutic response. The final section addresses the challenges and future perspectives in the field of nanomaterial-based drug delivery systems. Challenges include regulatory considerations, toxicity concerns, scalability, and clinical translation. Future directions involve the development of personalized nanomedicine, combination therapy approaches, and integration with other emerging technologies, such as artificial intelligence and gene editing. In conclusion, nanomaterial-based drug delivery systems have shown great potential for improving the efficacy and safety of therapeutic interventions. The advancements in nanotechnology offer exciting opportunities for the development of next-generation drug delivery platforms, opening new avenues for personalized medicine and targeted therapies. However, further research and collaborations are required to address the challenges associated with clinical translation and ensure the safe and effective implementation of these systems in clinical practice.

An analysis of the current landscape of therapeutics and delivery methods was conducted, aiming the field of drug delivery systems. Drug delivery biodistribution characteristics should be systematically understood, in order to maximize the function of these delivery systems. As a result, this review covers a history of the drug delivery systems, as well as the basic terminology associated with them, with a focus on the usage of polymers in the drug administration systems (particularly in form of coatings) and their application.
 New trends in nanomaterials-based drug delivery systems, primarily for cancer treatment, were presented, involving a technology designed to maximize therapeutic efficacy of drugs by controlling their biodistribution profile.
 There is a justified need to investigate drug delivery systems in form of thin films because, in comparation to bulk drug delivery system, which have a long and comprehensive history, there is still insufficient and fragmented understanding about the delivery of thin polymeric films, with research limited in general to very specific cases. Our efforts have been concentrated on these specifically polymeric drug delivery systems in the form of coatings. Understanding the dynamic changes that occur in a biodegradable polymeric thin film can aid in the prediction of the future performance of synthesized films designed to be used as implantable medical devices.
 Extensive research is required to continuously develop new therapeutic systems in order to achieve an optimal concentration of a specific drug at its site of action for an appropriate duration.

The effective treatment of ocular diseases is confronted by various factors, including ocular barriers, limited drug bioavailability, invasive procedures, and low patient compliance. Moreover, new ocular delivery systems have only overcome these problems to a certain extent. In response, smart ocular drug delivery systems have gained attention due to their ability to enable modified drug release along with the additional features they provide to the delivery system, the drug, and the treatment. Smart materials (endogenous and exogenous stimuli responsive) allow the carrier systems to exhibit a variety of properties. Studies on smart ocular drug delivery systems are relatively new and the interest in exogenous stimuli sensitive smart materials has increased in recent years. Therefore, in this review we focused on scientific advancements of these technologies to present a clear understanding of design principles which is key to developing more efficient and reliable ocular drug delivery systems. This review covers ocular barriers, diseases, drug delivery routes, conventional and novel ocular delivery systems along with a focus on the achievements of the smart ocular drug delivery systems developed in recent years. Special emphasis was given to the improved, reduced, or enabled properties of these drug delivery systems.

Silk fibroin has been widely used in biological fields due to its biocompatibility, mechanical properties, biodegradability, and safety. Recently, silk fibroin as a drug carrier was developed rapidly and achieved remarkable progress in cancer treatment. The silk fibroin-based delivery system could effectively kill tumor cells without significant side effects and drug resistance. However, few studies have been reported on silk fibroin delivery systems for antitumor therapy. The advancement of silk fibroin-based drug delivery systems research and its applications in cancer therapy are highlighted in this study. The properties, applications, private opinions, and future prospects of silk fibroin carriers are discussed to understand better the development of anti-cancer drug delivery systems, which may also contribute to advancing silk fibroin innovation.

BackgroundPolymeric drug delivery systems have been achieved great development in the last two decades. Polymeric drug delivery has defined as a formulation or a device that enables the introduction of a therapeutic substance into the body. Biodegradable and bio-reducible polymers make the magic possible choice for lot of new drug delivery systems. The future prospects of the research for practical applications has required for the development in the field.Main bodyNatural polymers such as arginine, chitosan, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid have been treated for polymeric drug delivery systems. Synthetic polymers such as poly (2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide)s, poly(ethylenimine)s, dendritic polymers, biodegradable and bio-absorbable polymers have been also discussed for polymeric drug delivery. Targeting polymeric drug delivery, biomimetic and bio-related polymeric systems, and drug-free macromolecular therapeutics have also treated for polymeric drug delivery. In polymeric gene delivery systems, virial vectors and non-virial vectors for gene delivery have briefly analyzed. The systems of non-virial vectors for gene delivery are polyethylenimine derivatives, polyethylenimine copolymers, and polyethylenimine conjugated bio-reducible polymers, and the systems of virial vectors are DNA conjugates and RNA conjugates for gene delivery.ConclusionThe development of polymeric drug delivery systems that have based on natural and synthetic polymers are rapidly emerging to pharmaceutical fields. The fruitful progresses have made in the application of biocompatible and bio-related copolymers and dendrimers to cancer treatment, including their use as delivery systems for potent anticancer drugs. Combining perspectives from the synthetic and biological fields will provide a new paradigm for the design of polymeric drug and gene delivery systems.

Traditional Chinese medicine (TCM) has a good curative effect, but its disadvantages include complex components, poor drug stability, potential drug interaction, etc. Therefore, it is particularly important to construct a novel drug delivery system that can load Chinese medicine monomers to solve this problem. Silk fibroin is a kind of natural polymer material with unique properties. It can be used as a carrier material to load Chinese medicine monomers to prepare novel drug delivery systems that significantly affect treating diseases without toxic and side effects. However, there is still a lack of a review on silk fibroin as a carrier material to load Chinese medicine monomers to explore and analyze the current research results and progress. Here, our article focuses on the in-depth excavation and analysis of the recent research on novel drug delivery systems prepared by silk fibroin and TCM monomers. Besides, the characteristics, existing problems, and prospects of silk fibroin are discussed and explained. It is hoped that this research can provide a reference and basis for the modernization of TCM, the design of novel drug delivery systems, the research and development of new drugs in the future, and contribute to the innovation of silk protein.