Drug Delivery using Nano-Material based Enzymes

Enzyme-responsive nanoparticles have emerged as a promising platform for targeted drug delivery, offering unparalleled control over therapeutic release in response to specific biological cues. This book chapter explores the design principles, mechanisms of action, and biomedical applications of enzyme-responsive nanoparticles in drug delivery. The chapter begins by elucidating the rationale behind the development of enzyme-responsive nanoparticles, highlighting the importance of precise drug release kinetics, site-specific targeting, and reduced off-target effects in enhancing therapeutic efficacy. Key design considerations, including choice of enzyme substrate, nanoparticle composition, and triggering mechanisms, are discussed in detail, emphasizing the versatility and tunability of these nanosystems for diverse therapeutic applications. Furthermore, the chapter delves into the underlying mechanisms governing enzyme-triggered drug release from nanoparticles, such as enzymatic cleavage, conformational changes, and degradation of nanoparticle matrices. Examples of enzyme-responsive nanomaterials, including liposomes, polymeric nanoparticles, and mesoporous silica nanoparticles, are presented, showcasing their ability to selectively release therapeutic payloads in response to specific enzymatic stimuli, such as proteases, phosphatases, and esterases. Moreover, the biomedical applications of enzyme-responsive nanoparticles are comprehensively reviewed, encompassing targeted cancer therapy, inflammation modulation, tissue engineering, and diagnostics. Case studies illustrating the efficacy of enzyme-responsive nanocarriers in overcoming biological barriers, improving drug bioavailability, and minimizing systemic toxicity are highlighted, underscoring their translational potential in clinical settings. The chapter concludes with a discussion of future perspectives and challenges in the field of enzyme-responsive nanoparticles for drug delivery, including optimization of nanoparticle stability, scalability of synthesis methods, and integration of imaging modalities for real-time monitoring of therapeutic responses. By harnessing the catalytic power of enzymes to orchestrate precise drug release, enzyme-responsive nanoparticles offer a paradigm shift in therapeutic precision, paving the way for personalized and targeted treatments with enhanced therapeutic outcomes.

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

The JALA Special Issue on Novel Drug Development and Delivery

Drug research and development has entered into the new epoch of innovation formulation, and the drug delivery system has been in the forefront of pharmaceutical innovation. Chitosan, a natural polysaccharide derived from chitin, due to its well-known biocompatibility and biodegradability, it has been widely used in drug delivery, immunostimulation, tissue regeneration, blood coagulation, wound healing, drug delivery and tissue engineering. Chitosan has become a valuable vaccine adjuvant and delivery carrier, which have attracted increasing attention for its applications. In this paper, we reviewed chitosan nanoparticles, which is a promising biomaterial as vaccine adjuvant and delivery carrier, including characteristics, preparation methods and applications, or even its limitations. We also investigated the mucosal immune delivery route for drug loaded chitosan nanoparticles, such as the routes of oral and nasal. Due to the low toxicity, better biodegradability and adhesivity of chitosan nanoparticles, it can be used as the delivery carrier of vaccine antigens and drugs. These promising studies laid a foundation for the applications of chitosan nanoparticles as a delivery carrier in the vaccine or drug. We undertook a structured research of biodegradable polymeric nanoparticles of chitosan used as a delivery carrier for the mucosal immunity of vaccine. We have searched the bibliographic databases for peer-reviewed research literature. The outstanding characteristics of the screened papers were described respectively, and a systematic content analysis methodology was used to analyse the findings. Sixty-three papers were included in the review, the majority defined leadership and governance approaches that had impacted upon the polymeric nanoparticles as the delivery carrier for the mucosal immunity of vaccine in therapeutic applications and developments. Thirty-five papers outlined the superiority characteristics of chitosan nanoparticles that applied in the field of vaccine. Twenty-eight papers overviewed the application prospects of chitosan derivatives used as drug delivery systerm. These included current advances in research and clinical applications of chitosan derivatives. This review identified the drug delivery systerm of chitosan or its derivatives, and we described the synthesis methods, applications and challenges of chitosan. The findings of this review identified that the chitosan derivatives were used as delivery carrier for vaccines. It also indicates that the chitosan or its derivatives play a vital role in the drug and vaccine delivery systerm.

The third Annual ARVO/Pfizer Ophthalmic Research Institute Conference was held Friday and Saturday, May 4 and 5, 2007 at the Fort Lauderdale Grande Hotel and Yacht Club, Fort Lauderdale, Florida. The conference, funded by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to develop strategies to address drug delivery to posterior intraocular tissues—a topic of great interest, as the major route of drug delivery is via intravitreous injection. A working group of 33 participants, focused interdisciplinary contributors, 19 observers from ARVO/Pfizer, and clinical and basic ophthalmic researchers convened to identify (1) unmet patient needs regarding current drug delivery, novel treatment of retinal diseases, the potential for novel drug design opportunities, drug delivery methods for targeted localized and sustained release, and delivery of macromolecules (siRNA, DNA); and (2) to evaluate the usefulness of nanoparticles, microbeads, and implants for drug delivery, as well as physical means of drug delivery (ionophoresis, electroporation, and microneedles). Session I: Unmet Needs and New Drug Opportunities in Treating Disorders of the Posterior Segment Session II: Animal Models of Posterior Ocular Diseases Session III: New Drug Design and Delivery Systems: What Do Experts See Beyond the Horizon? Session IV: Ocular Drug Delivery Using Nanoparticles, Microbeads, and Microneedles Session V: Transscleral, Intravitreous, and Suprachoroidal Drug Delivery Session VI: Ocular Tissue Dissection, Modeling, and Ocular Tissue Assays Session VII: Iontophoresis, Electroporation, Electrophoresis, and Photo-acoustic Delivery Each session began with a 10-minute introduction followed by a 30-minute lecture by a distinguished expert. Allan S. Hoffman, ScD, Professor of Bioengineering at the University of Washington, Seattle, presented “Design of Polymer Carriers for Intracellular Delivery of Biomolecular Drugs” and Mansoor Amiji, RPh, PhD, Professor and Associate Chairman of Pharmaceutical Science at Northeastern University (Boston, MA), presented “Nanotechnology for Advanced Drug Delivery.” During the remainder of each session, participants, and attendees discussed pertinent questions, voiced opinions, and identified unanswered questions. These discussions confirmed current and future needs for ocular drug delivery to the posterior segment.

Nanocarriers have emerged as promising drug delivery systems due to their unique properties and capabilities. This abstract provides an overview of the concept of nanocarriers as drug delivery systems, highlighting their significance and potential applications. The report begins by introducing the background and significance of drug delivery systems. It emphasizes the limitations of conventional drug delivery methods and the need for more efficient and targeted approaches. Nanocarriers offer a solution to these challenges by providing controlled and targeted drug delivery, leading to improved therapeutic outcomes. The advantages and challenges of nanocarriers as drug delivery systems are discussed. The advantages include enhanced drug stability, prolonged drug release, improved bioavailability, and targeted delivery to specific tissues or cells. However, challenges such as manufacturing complexity, regulatory considerations, and potential toxicity need to be addressed for successful clinical translation. The report then highlights the different types of nanocarriers used in drug delivery, including lipid-based nanocarriers, polymeric nanocarriers, and inorganic nanocarriers. Each type is briefly described, along with their synthesis methods, properties, and applications. The report also covers the principles of drug delivery using nanocarriers, focusing on the mechanisms of drug loading and release from nanocarriers. It discusses the factors influencing drug release kinetics and the strategies employed for enhanced drug delivery, such as targeting strategies. Finally, the report concludes by emphasizing the importance of nanocarriers in various therapeutic applications, including cancer drug delivery, central nervous system drug delivery, gene delivery, vaccines, and treatment of infectious diseases. It also highlights the future perspectives and challenges in the field of nanocarrier-based drug delivery systems.

Advanced drug delivery systems for therapeutic applications.

Enzyme-responsive nanoparticles for drug release and diagnostics

The ARVO 2012 Summer Eye Research Conference (SERC 2012) on “Drug and Gene Delivery to the Back of the Eye: From Bench to Bedside” was held June 15 and 16, 2012, at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The SERC provided a diverse group of approximately 150 scientists and physicians representing industry and academia from 14 countries with a unique opportunity to explore the latest approaches to drug and gene delivery to the posterior segment of the eye. Unlike the 2009 SERC meeting, which focused on novel drug delivery platforms while elucidating the anatomic barriers to reach the posterior segment,1 the most recent meeting explored strategies for bypassing ocular barriers using novel materials, nanoparticulate delivery systems, and gene therapy. It brought together experts in both ophthalmology and tangentially related areas to discuss the application and inherent technical challenges for translating experimental results from the laboratory bench to dependable medical therapies at the bedside and, where possible, it exemplified findings in ocular models with methods and results gleaned from disciplines outside of ophthalmology. The present review of the SERC provides investigators with tools to navigate these nascent approaches by exploring strategies from key laboratory investigations, drug development specialists, and clinical trials. The 2-day conference comprised the following six sessions: (1) barriers to drug delivery and transporter-guided drug design; (2) drug/gene delivery systems and cell therapies for the eye; (3) pharmacokinetics (PK), pharmacodynamics, and alternative routes of drug delivery; (4) nanotechnology for diagnosis and treatment of posterior eye disease; (5) translation of gene delivery for posterior eye disease; and (6) clinical trials. Rather than being a deliberate summary of each presentation, this review describes the common themes expressed during the six sessions.

PurposeAge-related eye diseases are becoming more prevalent. A notable increase has been seen in the most common causes including glaucoma, age-related macular degeneration (AMD), and cataract. Current clinical treatments vary from tissue replacement with polymers to topical eye drops and intravitreal injections. Research and development efforts have increased using polymers for sustained release to the eye to overcome treatment challenges, showing promise in improving drug release and delivery, patient experience, and treatment compliance. Polymers provide unique properties that allow for specific engineered devices to provide improved treatment options. Recent work has shown the utilization of synthetic and biopolymer derived biomaterials in various forms, with this review containing a focus on polymers Food and Drug Administration (FDA) approved for ocular use.MethodsThis provides an overview of some prevalent synthetic polymers and biopolymers used in ocular delivery and their benefits, brief discussion of the various types and synthesis methods used, and administration techniques. Polymers approved by the FDA for different applications in the eye are listed and compared to new polymers being explored in the literature. This article summarizes research findings using polymers for ocular drug delivery from various stages: laboratory, preclinical studies, clinical trials, and currently approved. This review also focuses on some of the challenges to bringing these new innovations to the clinic, including limited selection of approved polymers.ResultsPolymers help improve drug delivery by increasing solubility, controlling pharmacokinetics, and extending release. Several polymer classes including synthetic, biopolymer, and combinations were discussed along with the benefits and challenges of each class. The ways both polymer synthesis and processing techniques can influence drug release in the eye were discussed.ConclusionThe use of biomaterials, specifically polymers, is a well-studied field for drug delivery, and polymers have been used as implants in the eye for over 75 years. Promising new ocular drug delivery systems are emerging using polymers an innovative option for treating ocular diseases because of their tunable properties. This review touches on important considerations and challenges of using polymers for sustained ocular drug delivery with the goal translating research to the clinic.

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(N,N-dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding.

Polymeric micelles (PMs) have been the most popular and promising topic of many researches in the field of drug delivery and targeting for the past two decades. Polymeric micelles are the selfassembled nano-sized colloidal particles which are made up of amphiphilic block copolymers i.e. polymers consisting of hydrophobic block and hydrophilic block. In this highlight, we give an overview of the structure of micelles and polymeric micelles followed by a summary of the methods used for their preparation. We then focus on several kinds of PMs based on intermolecular forces such as polyion complex micelles (PICMs), non-covalently connected micelles (NCCMs) and recently developed smart polymeric assemblies which can respond to the application of external stimuli such as a change in temperature, pH, redox and light to afford novel nanomaterials. The types of polymers used in the preparation of PMs have also been highlighted so as to facilitate its use in drug delivery and targeting. These polymeric micelles nanocarriers have applications in drug delivery primarily such as anticancer therapy, to the brain to treat neurodegenerative diseases, antifungal agents, stimuli-responsive nanocarriers for drug and gene delivery, ocular drug delivery. Targeted drugs will hopefully reduce adverse reactions by limiting their action to cancer tissue only. Finally, this review broadly presents the basic aspects of PMs which help in delivery and targeting of actives with its recent advancements and applications. Key words: micelles, polymeric micelles, block copolymer, stimuli sensitivity

Since the previous decade, biodegradable polymeric nanoparticles have gained remarkable attention in pharmaceuticals industry. Poly(lactic- co -glycolic acid) (PLGA) is one of the outstanding biodegradable polymers. It is widely investigated for drug delivery, tissue engineering, and other biomedical applications. PLGA is considered as an excellent candidate for drug delivery due to its versatile characteristics. So, it is needed to gain basic knowledge of synthetic procedure and the physicochemical properties of polymer for developing polymeric drug delivery system. In this chapter, we have presented the PLGA synthesis strategies, physicochemical properties, chemistry of the polymer, degradation mechanism, and various applications in diverse fields such as drug delivery, tissue engineering, and other biomedical applications with its mechanism of action. As this chapter mainly focuses on the application of PLGA nanoparticles in drug delivery, various methods used for the synthesis of PLGA micro-/nanoparticles such as emulsion–evaporation method, emulsion–diffusion method, emulsion reverse salting-out method, phase separation method, spray-drying method, nanoprecipitation method, microfluidic method are discussed thoroughly. Moreover, the drug release mechanism form PLGA nanoparticle is presented schematically. Surface modification and functionalization strategies of PLGA micro-/nanoparticles are also highlighted. This chapter presents a comprehensive overview of PLGA-based nanoformulations for the treatment of several diseases including pulmonary diseases, ophthalmic diseases, cardiovascular diseases, neurodegenerative diseases, cancer, infections, and inflammations and also presents the future prospective of PLGA nanoparticles in drug delivery field.

Uniform, Scalable, High-Temperature Microwave Shock for Nanoparticle Synthesis through Defect Engineering

Objective TheDES are formed by mixing a Hydrogen Bond Donor (HBD) and a Hydrogen Bond Acceptor (HBA) in appropriate molar ratios. These solvents have been shown to enhance drug solubility, permeability, and delivery. The main objective of the present article is to review these advantages of TheDES. Significance TheDES show unique properties, such as low toxicity, biodegradability, improved bioavailability and enhanced drug delivery of poorly soluble active pharmaceutical ingredients. They are also biocompatible in nature which makes them a promising candidate for various therapeutic applications, including drug formulations, drug delivery and other biomedical uses. The development and utilization of TheDES shows significant advancement in pharmaceutical research, providing new opportunities for improving drug delivery. Methods The current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to demonstrate the effectiveness of TheDES in enhancing drug solubility, permeability, and delivery. All chosen articles were selected considering their significance, quality, and approach to addressing issues. Result As a result, various TheDES were identified that can be formulated in different ways: one component can act as a vehicle for an API, either HBD or HBA can be an API, both HBD and HBA can be APIs, or the individual components of DES are not therapeutically active but the resulting DES possesses therapeutic activity. Additionally, TheDES were also recognized to enhance drug delivery and solubility for different APIs, including NSAIDs, anesthetic drugs, antifungals, and others.