New year greetings from editors of Drug Delivery System

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

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.

A comparison between the effect of systemic and coated drug delivery in osteoporotic bone after dental implantation.

Part I: Pharmacological Considerations for Drug Delivery Systems in Cancer Medicine Systemically Administered Drugs Reginald B. Ewesuedo and Mark J. Ratain Regional Administration of Antineoplastic Drugs Maurie Markman Theoretical Analyses and Simulations of Anticancer Drug Delivery Ardith W. El-Kareh and Timothy W. Secomb Part II: Technologies Available for Use in Cancer Drug Delivery Systems Biopolymers for Parenteral Drug Delivery in Cancer Treatment Wolfgang Friess Hydrogels in Cancer Drug Delivery Systems Sung-Joo Hwang, Namjin Baek, Haesun Park, and Kinam Park Microparticle Drug Delivery Systems Duane T. Birnbaum and Lisa Brannon-Peppas Polyethylene Glycol Conjugation of Protein and Small Molecule Drugs: Past, Present, and Future Robert G. L. Shorr, Michael Bentley, Simon Zhsao, Richard Parker, and Brendan Whittle Emulsions As Anticancer Delivery Systems S. Esmail Tabibi Part III. Current Applications: Products Approved or in Advanced Clinical Development Liposomal Drug Delivery Systems for Cancer Therapy Daryl C. Drummond, Dmitri Kirpotin, Christopher C. Benz, John W. Park, and Keelung Hong Gliadel(R): A New Method for the Treatment of Malignant Brain Tumors Francesco DiMeco, Henry Brem, Jon D. Weingart, and Alessandro Olivi Intralesional Chemotherapy with Injectable Collagen Gel Formulations Elaine K. Orenberg Sustained-Release Drug Delivery with DepoFoam Sankaram B. Mantripragada and Stephen B. Howell Cancer Vaccines Susanne Osanto Part IV. Future Directions: Novel Cancer Drug Targets and Delivery Systems Gene Therapy of Cancer Susanne Osanto Progress in Antisense Technology Stanley T. Crooke Tumor Vaccines Francesco M. Marincola Diagnosis and Treatment of HumanDisease Using Telomerase As a Novel Target Lynne W. Elmore and Shawn E. Holt Index

Simulation-based approaches for drug delivery systems: Navigating advancements, opportunities, and challenges

Crossing Barriers From blood-to-brain and academia-to-industry

Проведено огляд літературних джерел щодо розробки та дослідження осмотичних систем вивільнення та доставки лікарських речовин

ABSTRACTIntroduction: Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer.Areas covered: The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering.Expert opinion: Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.

Drug delivery systems are now well developed and in use for various therapies. These systems surpass conventional mode of drug administration by efficiently delivering the desired concentrations of bioactive drug. Typically, drug delivery in the body is an interfacial phenomenon. Interaction of the administered carrier molecules with the body fluid depends on the physiochemical properties of the carrier molecules and hence controls its pharmacokinetics. However, nonspecific interactions and physiological stability of these molecules within biological systems may result in complications during the therapy and stimulate the immune responses. Also, the insolubility of hydrophobic drugs is a major problem in their therapeutic applications. Target-specific drug delivery with controlled interfacial interactions is a possible alternative to overcome these challenges. The regulation of interactions at biointerface allows modulating the in vivo administration of a carrier system. Various engineered nanomaterials, emulsion and polymer-based drug delivery systems, have been explored in the literature. Further, surface modifications and functionalization of these delivery systems are found to regulate interfacial interactions. The modification not only controls the reaction potency of drug with the biological systems but also enhances the stability and compatibility. This chapter describes the designing of engineered drug delivery systems using polymers, self-assembled monolayers, and emulsions. Application of these strategies to alter the surface chemistry of drug molecules and delivery systems is elaborated through recent studies. Bio-interfacial aspects of the above-designed systems are highlighted to confirm their fidelity to be used as effective drug delivery systems.

Chapter 11 - Carbon dots as carriers for the development of controlled drug and gene delivery systems

The provision of appropriate postoperative analgesia should be as important to modern surgery as is intraoperative anesthesia. Potent analgesics, such as morphine, have been available for several hundred years, yet our efficacy in treating acute postoperative pain was until recently abysmal. As late as 1983, 41% of patients rated their pain control inadequate after surgery [1]. The use of self-titration of an analgesic drug to provide postoperative pain management was first achieved in 1968 [2]. The ability to provide self-titration was dependent on developing an appropriate analgesic drug delivery device. It took years for industry to adopt this concept and to develop a commercial device. It also took physicians some time to recognize the utility of this approach to postoperative pain. It did not take patients long to demand patient-controlled analgesia (PCA), which is now widely practiced. There is no doubt that PCA provided a major step forward in the management of acute postoperative pain. Why has PCA provided a more satisfied patient with improved pain relief? Pain is a very subjective sensation, the effective concentration required for pain relief is extremely variable between patients (pharmacodynamic variability) as well as within patients, and lastly, any given dose will result in a different concentration in each individual due to the unique disposition of the drug in the individual (pharmacokinetic variability). In addition, safety is an issue. Potent opiate analgesics have a very narrow therapeutic margin, with doses exceeding the therapeutic concentration producing significant adverse effects (toxicity). Thus, the objective of any analgesic delivery system is to allow safe individual titration of drug dose so patients can maintain themselves within their own therapeutic window. PCA achieves this objective. There are, however, some theoretical disadvantages to PCA. Pain is the most intense soon after awakening. Thus, the required concentration of the analgesic is initially high. To attain an effective concentration requires some form of a large initial dose to fill the volume of distribution. To avoid exceeding the therapeutic concentration, multiple small doses of the opiate are given until adequate analgesia is obtained. For opiates like morphine, which equilibrate slowly from the blood to the brain and receptor, this equilibration period can take several hours. Also, due to redistribution and elimination, once the peak effect of the drug is achieved, drug concentration is continuously decreasing. Thus, PCA does not totally avoid the peaks and valleys of intermittent intramuscular injection, but simply makes them smaller. While PCA has been widely accepted clinical practice, further technologic developments are occurring to further improve drug delivery. Certainly, on a theoretical basis, it is ideal to administer drugs to a target effect (i.e., the clinician sets the targeted effect, e.g., degree of neuromuscular blockade, and the delivery system simply adjusts the dosing rate to achieve this monitored response). Unfortunately, neither anesthesia nor analgesia has readily measurable or quantifiable end-points. Thus, the next best is to be able to administer the drug to an effective concentration. By using pharmacokinetic parameters derived from the disposition of the drug, it is possible to program a computer so that it calculates the dosing regimen necessary to achieve the target plasma concentration (thereby automatically providing the initial loading of the drug) [3]. The efficacy of such devices for the administration of intravenous drugs during anesthesia has been evaluated in many studies over the past 15 yr [3]. Using pharmacokinetic-pharmacodynamic modeling, it is also possible to program the drug delivery device not only to target a plasma concentration but also to target an effect site concentration (i.e., the concentration that is in equilibration with the site of drug effect, e.g., the opiate receptor) [4,5]. This prevents much of the time delay that occurs as the plasma concentration equilibrates with drug receptors in the brain. For example, if a target plasma concentration of fentanyl is selected, it will take approximately 20 min before the full effect of this concentration is observed, whereas if a target effect site concentration is selected the full effect will occur within 3-5 min. Such computer controlled infusion devices [computer assisted continuous infusion (CACI) [6]] can be programmed to almostly instantaneously produce a desired effect concentration and then maintain this concentration. It is a logical step to combine PCA with CACI devices so that patients can rapidly attain and maintain an effective concentration of the analgesic. In this issue of Anesthesia & Analgesia, van den Nieuwenhuyzen et al. [7], although not the first to use such a system, are the first to try to compare the possible advantages of CACI-PCA (referred to as CCIA in their paper) with those of conventional PCA for postoperative pain management. Their results strongly support the superiority of CACI-PCA over conventional patient-controlled administration. This is based on a more rapid achievement of satisfactory analgesia, the time patients spent at the desired level on the visual analog pain scale (VAS; VAS less than 3), and the total number of doses requested by the patient. The CACI-PCA results favoring target-controlled infusion for PCA need to be carefully reviewed. Unfortunately, the authors chose to compare two different drugs using two different delivery modes. It is difficult to determine whether the advantageous results were due to the drug or the delivery system. Alfentanil has a very rapid onset of effect as evidenced by its ke0 (the ke0 represents the rate of equilibration between the plasma and the effect site). The ke0 for morphine has not been established, but is considered to be considerably longer than that of alfentanil. The more rapid onset of effective analgesia with target-controlled alfentanil could largely be explained by these differences in ke0 rather than the drug delivery system. Similarly, it is noted that the greatest difference in the time period for which there was a VAS of greater than 3 between the two groups was from 0 to 8 h. This again may simply be explained by the slower onset of effective analgesia with morphine compared to alfentanil, rather than the delivery system. In addition, the incremental doses delivered with each demand may not have been truly equally efficacious; thus, it may have required two demands for morphine to provide the same degree of analgesic relief as one demand for alfentanil. This difference would then readily explain the differences in demand and continued differences in time above a VAS of 3 between the two groups. Of interest and noted by van den Nieuwenhuyzen et al., PCA alfentanil has not provided effective postoperative pain management when given with a conventional PCA device. The authors have demonstrated that when alfentanil is administered using target CACI-PCA for postoperative pain management, it is definitely superior to conventional PCA morphine in providing postoperative pain relief. From this we can infer that through the utilization of CACI-PCA alfentanil becomes a more suitable opiate for postoperative pain management. One of the primary advantages of CACI drug delivery for postoperative analgesia is that it will maintain the drug level within the therapeutic window for longer periods of time. This argument should similarly hold true when using a low-dose continuous infusion in combination with PCA. The combination of a continuous infusion plus PCA has resulted in a greater number of side effects and greater opiate use but no greater pain relief [8]. A possible explanation for this is that pain, after surgery, does not remain constant, but rather is constantly changing. The advantage of a standard PCA regimen is that no drug is being delivered when pain is decreasing or is minimal. It would therefore seem that the ideal delivery system should rapidly achieve an effective concentration and that this concentration should not necessarily be maintained, but should decrease over time to enable patients to keep themselves within their own changing therapeutic window. van den Nieuwenhuyzen et al. [7] in this study creatively addressed this problem by forcing the target-controlled concentration to decrease after 2 h if no patient demand had been made. Is 2 h an appropriate time interval to wait? CACI drug delivery usually uses a single pharmacokinetic set to represent the entire patient population. van den Nieuwenhuyzen et al. demonstrated that the pharmacokinetics of Maitre et al. [9] provided minimal bias and a low-median absolute performance error. This does not exclude the possibility that in any individual patient, over a 2-h period, the target concentration is increasing with the possibility of significant respiratory depression. When evaluating patients on morphine PCA, the authors' philosophy is to adjust the PCA dose to provide one to two patient-demanded doses per hour. Thus, to wait 2 h without a demand prior to allowing the concentration to decrease may be to wait too long. Fortunately, a CACI drug delivery system can be programmed to start decreasing the target concentration at any specified time. Another feature of CACI-PCA that needs to be addressed is the size of the maintenance dose. Most potent opiates have a very steep concentration effect, so it will be necessary to establish appropriate and safe increments in opiate concentration with each demand. Thus, it is important to first confirm the optimal settings for a CACI delivery system when used in the patient-controlled mode, and then compare this to the traditional bolus method of patient-controlled analgesia using the same drug. The use of target-controlled drug delivery in a postoperative setting is relatively new. CACI has established itself as an important tool for the intravenous administration of drugs during anesthesia. As a drug delivery system, CACI is akin to the calibrated vaporizer, which is accepted as the standard delivery system for volatile anesthetics. CACI drug delivery has also proven to be more efficacious than intermittent bolus administration and at least equal to a manual infusion system [10]. As a tool CACI has enabled anesthesiologists to define the concentration effect relationship of drugs used in anesthesia, as well as the effect resulting from the interaction between intravenous drugs providing anesthesia [3]. In addition, CACI has enhanced our understanding of the pharmacokinetic and pharmacodynamic principles related to intravenous administration of anesthetic drugs. Like the concept of PCA, target-controlled drug delivery is dependent on having an accessible device. This is largely dependent on industry embracing this concept and providing a commercial device. The paper by van den Nieuwenhuyzen et al. [7] further demonstrates the use and potential of target-controlled drug delivery within our speciality. We predict with certainty and enthusiasm that, when industry and the regulatory agencies produce a CACI device, it will be widely accepted as another step forward in the never-ending quest to optimize patient care.

Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment

Drug delivery systems (DDS) have been the focus of intense research for several decades. Many approaches and strategies have been employed over the years, further expanding this field. For example, the advancements towards targeted drug delivery (TDD) enabled the use of DDS for diagnostic purposes. In addition, DDS research has provided the foundation for tissue engineering and theranostic systems (therapeutic systems with diagnostic properties). Drug delivery research has yielded many successes over the years with a significant amount of therapeutic and diagnostic products out in the market. Nevertheless, many challenges still remain. Herein, in this special edition, we asked various experts to review recent advancements in their field of expertise and report their latest findings. The special edition is well balanced and is comprised of 60% reviews and 40% research articles. One may find up-to-date reviews on advancements made in biomaterials, noninvasive drug delivery, drug conjugations, biosensors, diagnostics, implantable and ingestible devices, nanomaterials, cancer treatment, and endosome-derived vesicles. Additionally, research articles are provided, describing advanced new designs of microneedles (MNs), approaches to enhance tissue engineering capabilities, biomaterials, and DDS. The global market of protein- and nucleotide- based pharmaceutics accounted for $643 million in 2016, and is anticipated to reach over $8000 million by 2028. However, the use of these therapeutics is hindered by issues of immunogenicity, high molecular weight, fast renal clearance, and enzymatic degradation. For these reasons, to date, monoclonal antibodies (mAbs) are administered only via injection. Considering that, Angsantikul et al. propose the use of ionic liquid and eutectic solvent for the oral delivery of mAbs (article number 2002912). Their system reduced the mucosal viscosity and enhanced the paracellular transport of TNFα antibody in vitro. Additionally, Rondon and colleagues review the latest advancements in polymer chemistry and protein engineering in order to overcome part of these limitations (article number 2101633). Another approach to overcome these limitations is by using antibody-drug conjugates (ADCs). Accordingly, Firer and Luboshits review the recent developments employed in ADCs for the treatment of hematological malignancies (article number 2100032). They focus on the important link between the biology of the ADC and clinical efficacy, highlighting newer developments that strengthen this link to provide long-term clinical benefits. One of the most important purposes of drug delivery is achieving TDD. Dacoba and colleagues provide an overview on the concepts of passive and active targeting while exploring current venues for nanotechnology to solve the problems associated with drug delivery (article number 2009860). TDD is especially important for cancer therapy since killing cancerous cells is quite facile, but killing only cancerous cells is extremely challenging. Fu et al. review the latest strategies employed to overcome the barriers of chimeric antigen receptor T cells therapy in solid tumors (article number 2009489). Brain therapy is another challenging route for drug delivery requiring specific TDD system. To this end, Buaron et al. have developed a novel pectic galactan-based gene therapy approach that targets reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 (article number 2100643). Their biocompatible pectin galatcan-plasmid DNA complexes were selectively transfected to glial cells in cortical lesions. Moreover, Avital et al. report their interesting application for nanosized DDS—foliar delivery of siRNA for treating grapevine leafroll associated virus-3 (GLRaV-3) infection that causes major economic losses (article number 2101003). By exploiting a lipid-modified polyethylenimine carrier, they show that a single dose can knock down GLRaV-3 titer, and multiple doses keeps the viral titer at baseline, which triggers the recovery of the vine and berries. Another important aspect of drug delivery research is the development of noninvasive drug administration routes. Rahamim and Azagury review the origins of biomimetic, bioinspired, and bioengineered noninvasive DDS and achievements made in the last decade (article number 2102033). Additionally, Zhang et al. review advances in DDS that access the ear through the tympanic membrane (article number 2008701). Transdermal drug delivery is one of the most used noninvasive drug delivery routes. An exciting approach for transdermal drug delivery is microneedles (MNs). Puigmal and colleagues propose applying MNs array to treat severe burns that simultaneously sample immune cells in the interstitial fluid to diagnose the response (article number 2100128). Their MNs design enables the local delivery of pharmaceutics—the chemokine CCL22 and the cytokine IL-2—thus increasing local immuno-suppression. They found that the immune cell population in the allograft and MN were similar so they can be harvested from the MN for downstream analysis. Moreover, Li et al. have also proposed an improved MNs design where they use a biphasic dissolvable MN patch with water-insoluble backing in order to tackle insufficient drug delivery with MN (article number 2103359). Their new design enables a drug delivery efficiency of >90% into the skin within 5 min. Biomaterials are the building blocks of drug delivery, diagnostics, and tissue engineering research. Therefore, there is an ever-growing need for novel biomaterials with new functionalities and improved properties. To this end, Arun et al. present an exclusive coverage of biocompatible injectable pasty or liquid polymers without the use of any solvent for drug delivery and regenerative medicine applications (article number 2010284). Moreover, Khait et al. review novel biomaterial-based strategies used to modulate the immune response post ischemic stroke while providing their perspective on the potential clinical translation of these therapies (article number 2010674). Additionally, Redenski et al. developed a new composite tissue made of soft-tissue matrices and decellularized bone for bone defect repair (article number 2008687). The use of their novel tissue composite supported a long-term bone defect repair, as well as muscle defect bridging. These aforementioned applications and additional applications use cell-based therapeutics. The major obstacles of cell-based therapeutics are their low yields (i.e., difficult to scale-up), insufficient drug loading, and inconsistencies. For this reason, Guo et al. have developed a scaled-up and facile magnetic-based extrusion method for preparing endosome-derived vesicles (article number 2008326). An additional application of diagnostics and therapeutics is implantable and ingestible devices. In this special edition, Yang and colleagues provide an up-to-date review on the state-of-the-art of powering technologies for implantable and ingestible electronics—one of the greatest challenges for ingestible devices (article number 2009289). Welch et al. have focused their review on the complex hierarchical nano-structures and nano-materials used in biosensors and diagnostic technologies (article number 2104126). Additionally, they discuss their unique advantages and clinical applications while proposing future directions. In this special edition Nakonechny and Nisnevitch provide an up-to-date review focused on ultrasound applications used to combat infections caused by microorganisms, and to promote the local release of antimicrobial drugs from liposomes and medical implants (article number 2011042). Precise and well-controlled scaffolds are highly desired for tissue engineering and regenerative medicine purposes. For example, Dubay et al. review the recent achievements of single-cell microgels and their potential alternatives, which are used when single cell resolution is needed, for example—modular bio-inks and 3D cellular microenvironments (article number 2009946). Another challenge for implantable devices is a foreign body response (FBR). Kutner et al. review the recent advantageous technologies used to overcome the FBR effect via surface modifications and localized DDS (article number 2010929). One such surface modification is reported by Israeli et al. who developed a general and versatile technology to engineer light-responsive protein-based biomaterials (article number 2011276). These novel biomaterials—consist of azobenzene containing elastin-like polypeptides—are capable of forming self-assembled nanostructures and exhibit a reversible, light-mediated phase transition, with up to a 12 °C difference in the transition temperature. We are certain that this assemblage of reviews and research papers on the use of DDS for therapeutic and diagnostic purposes is of high interest for anyone working in this field. It provides up-to-date reviews on state-of-the-art topics and research papers with promising results to further propel drug delivery research. Understanding what has been done in the past, while learning of new approaches and techniques, is crucial for any scholar who wishes to advance their personal research. Joseph Kost D.Sc. is a University Distinguished Professor, he holds The Abraham and Bessie Zacks Chair in Biomedical Engineering and was the Dean of the Faculty of Engineering Sciences at Ben-Gurion University of the Negev (BGU). He is a member of AIMBE, NAE, CRS, and the Israel Academy of Sciences and Humanities. His research interests are in the fields of biomedical engineering, biomaterials science, controlled drug delivery, gene therapy, and ultrasound. Edith Mathiowitz is a full Professor of Medical Science and Engineering at Brown University, Department of Department of Pathology and Laboratory Medicine. She Is an AIMBE, CRS, and NAI fellow member. She founded and directed the ABC/Biotechnology Graduate Program at Brown. Her interdisciplinary research is focused on developing smart oral bioadhesive delivery systems and novel insights in polymer morphology. Her laboratory serves as an incubator for several start-up companies such as Spherics, Perosphere, and Therapyx. Aharon (Roni) Azagury is an Assistant Professor in the Department of Chemical and Biotechnology Engineering in Ariel University. He received his PhD in chemical engineering from BGU. He is a member of the CRS, ICRS, and NAI societies. His current research focuses on developing novel noninvasive biomimetic and bioinspired drug delivery systems.

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.

Nanogels are hydrogels with nanometer-scale three-dimensional networks of physically or chemically cross-linked chains. Nanogels have attracted much interest in recent years for various biomedical applications such as drug delivery systems and bioimaging owing to their specific properties of size tunability and intrinsic hydrophilic surfaces. Nanogels are generally classified either as natural polymer-based or synthetic polymer-based nanogels. Natural polymer-based nanogels are considered better candidates for drug delivery than synthetic polymer-based nanogels. This review summarizes the role of natural polymer-based nanogels, especially carbohydrate-based nanogels as drug and gene delivery systems.