Targeted immunomodulation for chronic diseases through advanced delivery platforms

Controlled Drug Delivery Systems (CDDS) represent a significant advancement in pharmaceutical technology, designed to deliver therapeutic agents in a controlled and sustained manner over an extended period. These systems aim to optimize the drug's efficacy by maintaining therapeutic drug levels in the body, reducing side effects, and enhancing patient compliance. CDDS can be classified into various categories, including polymeric, liposomal, and nanoparticle-based systems, each offering unique benefits. Polymeric systems, for example, allow for the precise release of drugs through diffusion, degradation, or swelling mechanisms. Drugs can be targeted to certain tissues with the use of liposomes and nanoparticles, increasing the therapeutic index while lowering systemic exposure. To further improve the accuracy of drug administration, CDDS can also be made to react to environmental stimuli like pH, temperature, or electromagnetic fields. The creation of CDDS has been the subject of extensive research in recent decades in order to solve issues such patient adherence, drug stability, and bioavailability. With the development of new materials and technology, CDDS remains a promising treatment option for cancer, chronic diseases, and other complex medical problems, offering more individualized and efficient therapeutic alternatives.

Controlled drug delivery has been attracting a great deal of attention in the medical community for years as an efficient way of providing treatment for a wide class of diseases. The common principle on which various drug delivery devices are based is mass transfer of the given drug toward particular organs, in which either the mass transfer rate, or place, or both are prescribed according to certain medical protocols. Much progress has been achieved in the design and development of various controlled drug delivery systems, and many people routinely take medicine designed for controlled release. Mathematical modeling of drug delivery systems is very important because a successful model can provide a better understanding and a quantitative description of the physical, chemical and biological processes governing the performance of the systems. On the basis of this description, better controlled drug delivery systems can be designed. We hope that this collection of papers will result in an increased attention of applied mathematicians to this class of important mass transfer and control problems. We also hope that practitioners will become more aware of the mathematical results that can be useful. The papers differ in mathematical sophistication, ranging from models described by systems of ODEs to quite complex PDE problems. They consider quite a few different aspects of drug delivery thus introducing a significant portion of the field. Each paper has an extensive introduction that should make the paper understandable to an applied mathematician who is not an expert in drug delivery. A discussion of controlled drug delivery in cancer immunotherapy is presented in “Controlled Drug Delivery in Cancer Immunotherapy: Stability, Optimization, and Monte Carlo Analysis" by Minelli, Topputo, and Bernelli-Zazzera, who formulate and solve an optimal control problem and show that the control policy is effective even when the patient's initial conditions are uncertain. A hybrid model of cell population dynamics, where cells are discrete elements whose dynamics depend on continuous intracellular and extracellular processes, is developed in “Hybrid Model of Erythropoiesis and Leukemia Treatment with Cytosine Arabinoside" by Kurbatova, Bernard, Bessonov, Crauste, Demin, Dumontet, Fischer, and Volpert, to simulate the evolution of immature red blood cells in the bone marrow. The model is used to study normal and leukemic red blood cell production and treatment of leukemia. In “Quadratic Models to Fit Experimental Data of Paclitaxel Release Kinetics from Biodegradable Polymers," Blanchet, Delfour, and Garon validate three ODE models against experimental data in order to better understand drug release kinetics. A model for drug diffusion from a spherical polymeric drug delivery device is considered in “Asymptotic and Numerical Results for a Model of Solvent-Dependent Drug Diffusion through Polymeric Spheres" by McCue, Hsieh, Moroney, and Nelson. Here the solvent diffuses into the polymer, which transitions from a glassy to a rubbery state, thus resulting in a moving boundary problem. In “Model Reduction Strategies Enable Computational Analysis of Controlled Drug Release from Cardiovascular Stents," D'Angelo, Zunino, Porpora, Morlacchi, and Migliavacca deal with drug-eluting stents and consider a hierarchy of mathematical models ranging from a lumped ODE model to fully three-dimensional models for drug transfer in the artery. A gene delivery of nucleic acid to the cell nucleus problem is discussed in “Modeling the Early Steps of Cytoplasmic Trafficking in Viral Infection and Gene Delivery," in which Amoruso, Lagache, and Holcman focus on plasmid DNA and virus cytoplasmic trafficking. The editors thank all the authors and reviewers for their contributions to this collection.

Stomach-specific mucoadhesive microspheres as a controlled drug delivery system have been developed to increase gastric retention time of the dosage forms. It is known that differences in gastric physiology, such as gastric pH and motility, exhibit both intra- as well as inter-subject variability demonstrating significant impact on gastric retention time and drug delivery behavior. This article presents the polymers use for mucoadhesive microsphere, factor affecting the mucoadhesion, and preparation techniques of mucoadhesive microsphere. Developments in the techniques for in vitro and in vivo evaluation of mucoadhesive microspheres have also been discussed. How to Cite this Article Pubmed Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB. Mucoadhesive Microsphere as a Controlled Drug Delivery SRP. 2010; 1(1): 70-78. doi:10.4103/0975-8453.59515 Web Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB. Mucoadhesive Microsphere as a Controlled Drug Delivery http://www.sysrevpharm.org/?mno=302644633 [Access: March 28, 2021]. doi:10.4103/0975-8453.59515 AMA (American Medical Association) Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB. Mucoadhesive Microsphere as a Controlled Drug Delivery SRP. 2010; 1(1): 70-78. doi:10.4103/0975-8453.59515 Vancouver/ICMJE Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB. Mucoadhesive Microsphere as a Controlled Drug Delivery SRP. (2010), [cited March 28, 2021]; 1(1): 70-78. doi:10.4103/0975-8453.59515 Harvard Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB (2010) Mucoadhesive Microsphere as a Controlled Drug Delivery SRP, 1 (1), 70-78. doi:10.4103/0975-8453.59515 Turabian Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB. 2010. Mucoadhesive Microsphere as a Controlled Drug Delivery Systematic Reviews in Pharmacy, 1 (1), 70-78. doi:10.4103/0975-8453.59515 Chicago Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB. Stomach-Specific Mucoadhesive Microsphere as a Controlled Drug Delivery System. Systematic Reviews in Pharmacy 1 (2010), 70-78. doi:10.4103/0975-8453.59515 MLA (The Modern Language Association) Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB. Stomach-Specific Mucoadhesive Microsphere as a Controlled Drug Delivery System. Systematic Reviews in Pharmacy 1.1 (2010), 70-78. Print. doi:10.4103/0975-8453.59515 APA (American Psychological Association) Style Rajput G, Majmudar F, Patel J, Thakor R, Rajgor NB (2010) Mucoadhesive Microsphere as a Controlled Drug Delivery Systematic Reviews in Pharmacy, 1 (1), 70-78. doi:10.4103/0975-8453.59515

Next Generation Immunotherapies – Emerging Strategies for Immune Modulation against Cancer, Infections, and Beyond

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.

Comparative evaluation of various structures in polymer controlled drug delivery systems and the effect of their morphology and characteristics on drug release

Polymeric smart materials have a significant role in providing tuneable and sustained release of both hydrophilic and hydrophobic drugs. This chapter is a review on the use of swelling controlled drug delivery systems in the pharmaceutical industry, examining the evolution of swellable polymeric materials into effective delivery systems for therapeutic agents. Within the sub-classes of swelling devices, swellable matrices and superdisintegrants, the discussion of swellable controlled drug delivery devices and systems focus on their structures, properties, and swelling mechanisms. Major factors influencing the manner of drug release will also be investigated, as will mathematical models used to predict drug release characteristics. In the final section, the potential drawbacks of swellable controlled drug delivery systems will be discussed.

Bioadhesive microspheres as a controlled drug delivery system

The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.

Hot-melt extrusion (HME) technology is rapidly growing in the pharmaceutical industry over recent years to provide the industry's most groundbreaking drug delivery technologies. Considering the continuously changing regulatory requirement where there is a constant demand for high production efficiencies with cost-saving and superior product quality, this well-established technology provides easy scale-up and process optimization. Controlled drug delivery systems (CDDS) offer a once-daily dose that is sufficient to maintain consistent plasma levels and provide maximal therapeutic value. Extruded CDDS have been proven effective for oral delivery. The objective of this chapter is to provide a pragmatic guide for research formulators to adapt in making formulation decisions and to understand the HME processing condition at a molecular level. This chapter presents the journey and evolution of CDDS along with case studies utilizing HME, offering myriad solutions for healthcare benefits. This chapter also highlights the specific challenges faced in the development of CDDS.

Medicinal Research ReviewsVolume 1, Issue 4 p. 373-386 Article Systems for controlled drug delivery Alejandro Zaffaroni, Alejandro Zaffaroni ALZA Corporation, 950 Page Mill Road, Palo Alto, California 94304 Alefandro Zaffaroni is noted for his contributions to steriod biochemistry and for his pioneering accomplishments in the field of controlled drug delivery. A native of Montevideo, Uruguay, Dr. Zaffaroni received his Ph.D. from the University of Rochester. At Syntex Corporation, which he joined in 1951, he became Executive Vice President, President of Syntex Laboratories, and President of Syntex Research. in 1968, he left Syntex and established ALZA Corporation to develop more physiologic approaches to drug therapy. Under his direction, ALZA Corporation to develop more physiologic approaches to drug therapy. Under his direction, ALZA has developed innovative systems-for routine use via the oral, injectable, transdermal, intravenous, and topical routed-that deliver drugs at precisely controlled rates over prolonged durations following one application. More recently, Dr. Zaffaroni founded and became Chairman of the Board of DNAX, Ltd., a privately funded corporation in which ALZA holds a minority interest. The new company will develop macromolecular products for medicine by combining the technologies of genetic engineering, immurobiology, and advanced drug delivery systems.Search for more papers by this author Alejandro Zaffaroni, Alejandro Zaffaroni ALZA Corporation, 950 Page Mill Road, Palo Alto, California 94304 Alefandro Zaffaroni is noted for his contributions to steriod biochemistry and for his pioneering accomplishments in the field of controlled drug delivery. A native of Montevideo, Uruguay, Dr. Zaffaroni received his Ph.D. from the University of Rochester. At Syntex Corporation, which he joined in 1951, he became Executive Vice President, President of Syntex Laboratories, and President of Syntex Research. in 1968, he left Syntex and established ALZA Corporation to develop more physiologic approaches to drug therapy. Under his direction, ALZA Corporation to develop more physiologic approaches to drug therapy. Under his direction, ALZA has developed innovative systems-for routine use via the oral, injectable, transdermal, intravenous, and topical routed-that deliver drugs at precisely controlled rates over prolonged durations following one application. More recently, Dr. Zaffaroni founded and became Chairman of the Board of DNAX, Ltd., a privately funded corporation in which ALZA holds a minority interest. The new company will develop macromolecular products for medicine by combining the technologies of genetic engineering, immurobiology, and advanced drug delivery systems.Search for more papers by this author First published: Winter 1981 https://doi.org/10.1002/med.2610010404Citations: 14 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume1, Issue4Winter 1981Pages 373-386 RelatedInformation

Decision makers request increasingly for high levels of evidence when allocating resources in medical care. This is hardly feasible for rare diseases. The objective was to analyze clinical and economic aspects of different immune tolerance induction (ITI) strategies for children with severe haemophilia A and inhibitors. A decision model, time frame 18 years (base case: 2 year old boy), was constructed from a German statutory health insurance (SHI) perspective. Compared were high-dose (HD) ITI, low-dose (LD) ITI, 'ITI with risk assessment', on-demand (OD) treatment with bypassing agents. Clinical data were derived from structured literature research and expert opinion. Sensitivity analyses were conducted for parameters with wide statistical ranges. Base case analysis: total costs for HD ITI amounted to €3.4 million with 40.9% ITI costs, 51 joint bleeds, 36 hospital days; LD ITI, €2.4 million with 21.4% ITI costs, 74 joint bleeds, 52 hospital days; 'ITI with risk assessment', €2.7 million with 27.6% ITI costs, 53 joint bleeds, 37 hospital days; OD treatment, €1.7 million, 146 joint bleeds, 104 hospital days. Incremental costs per bleed avoided with HD ITI decreased from €1 million to €0.15 million with increase of joint bleeds from 3 to 20 per year, when compared to 'ITI with risk assessment' in sensitivity analysis. 'ITI with risk assessment' is cost-saving with comparable outcomes to HD ITI. However, patient-related factors like bleeding frequency have to determine treatment decisions in individual patients. More clinical data is needed to increase the significance of model -calculations.

Controlled drug delivery systems are crucial for maintaining therapeutic efficacy while minimizing side effects. However, they have long presented a significant challenge in the field of medicine. It is difficult to precisely control the drug release kinetics with conventional drug delivery methods, leading to reduced effectiveness and potential toxicity. As a result, there is an increased demand for advanced drug delivery platforms, capable of providing precise and sustained drug release, thereby improving performance and patient outcomes. Implantable microchips are advanced microelectromechanical systems-based devices that have the potential to revolutionize drug delivery and are the preferred choice for researchers and industry pioneers. They are a promising and superior alternative to traditional systems, as they are biocompatible, easy to manufacture, and have patient-friendly designs. Microchips are designed to provide precise control over both the rate and timing of drug release. A single microchip can be engineered with multiple reservoirs (loaded with different active moieties) via different microfabrication techniques, enabling multi-drug therapy. Currently, most implantable microchips are designed as single-use devices, intended to be removed or replaced once the drug reservoirs are depleted. Nevertheless, research is ongoing to address this issue, and efforts are being made to design refillable microchips. They have a wide range of applications, including chronic disease management for conditions like diabetes and cardiovascular diseases, cancer therapy, and treatment of neurological disorders like Parkinson's disease. The current review offers a comprehensive exploration of the evolution of implantable microchips for drug delivery, tracing their development from inception to the latest advancements along with their working methods and fabrication technologies.

Aim: Chitosan-dialdehyde cellulose/DAC-based injectable hydrogel for controlled release of Metformin. Materials and Methods: Biomaterial-based injectable hydrogel was prepared by incorporating chitosan and dialdehyde cellulose. Dialdehyde cellulose (A cross-linker) was prepared by periodate oxidation method. The antidiabetic agent metformin was easily mixed with the chitosan and dialdehyde cellulose cross-linked solution, for the controlled drug delivery applications. The prepared injectable hydrogel showed the shear thinning property. Results: IR spectra confirmed the presence of cross-linked network between chitosan and dialdehyde cellulose. The physical appearance, injectability, pH, sol–gel phase transition, drug content, DSC, FTIR, and SEM studies were investigated. DSC and SEM studies revealed the degradation pattern and the topographical nature of prepared injectable hydrogel, respectively. The %drug release of metformin was found to be 87.25% prolonged for 84 h. The drug release pattern revealed the effective controlled drug delivery of metformin as compared to marketed tablet formulation. Conclusion: The study suggested that the controlled drug delivery system can be incorporated into the injectable hydrogel system; it would be more potential as compared to conventional controlled drug delivery system and preformed hydrogel system.

9 - Thermo- and ultrasound-responsive polysaccharides for controlled drug delivery