Conventional Drug Administration Research Articles

Fabrication of hydrogel mini-capsules as carrier systems

Conventional drug administration often results in systemic action, thus needing high dosages and leading to potentially pronounced side effects. Targeted delivery, employing carriers like nanoparticles, aims to release drugs at a target site, but only a small fraction of nanoparticles actually reaches it. Microrobots have been proposed to overcome this issue since they can be guided to hard-to-reach sites and locally deliver payloads. To enhance their functionality, we propose microrobots made as deformable capsules with hydrogel shells and aqueous cores, having the potential added advantages of biocompatibility, permeability, and stimulus-responsiveness. Endowing microrobots with deformability could allow them to navigate inside capillaries and cross barriers to finally reach the target site. In this study, we present a cost-effective method for fabricating core-shell structures without the use of organic solvents, surfactants, or extreme pH conditions unlike other techniques (e.g. Layer by Layer). The process begins with the dripping of a mixture of hydrogels, agarose and alginate, into a solution to gelate the drops into beads. After they are loaded with calcium ions at different concentrations, they are immersed in an alginate solution to form the shell. Finally, the beads are heated to let the agarose melt and diffuse out, leaving a liquid core. By varying the concentration of calcium ions, we obtain shells of different thicknesses. To estimate it, we have developed a method using the colour intensity from microscope images. This allowed us to observe that lowering the calcium ions concentration below a threshold does not lead to the formation of continuous shells. For higher concentrations, although the core may remain partially gelled, continuous shells successfully form. Therefore, our fabrication process could find applications in drug delivery, encapsulation systems, and microrobotics.

Novel Drug Delivery Systems: An Important Direction for Drug Innovation Research and Development.

The escalating demand for enhanced therapeutic efficacy and reduced adverse effects in the pharmaceutical domain has catalyzed a new frontier of innovation and research in the field of pharmacy: novel drug delivery systems. These systems are designed to address the limitations of conventional drug administration, such as abbreviated half-life, inadequate targeting, low solubility, and bioavailability. As the disciplines of pharmacy, materials science, and biomedicine continue to advance and converge, the development of efficient and safe drug delivery systems, including biopharmaceutical formulations, has garnered significant attention both domestically and internationally. This article presents an overview of the latest advancements in drug delivery systems, categorized into four primary areas: carrier-based and coupling-based targeted drug delivery systems, intelligent drug delivery systems, and drug delivery devices, based on their main objectives and methodologies. Additionally, it critically analyzes the technological bottlenecks, current research challenges, and future trends in the application of novel drug delivery systems.

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport.

The nose-to-brain drug-delivery system has emerged as a promising strategy to overcome the challenges associated with conventional drug administration for central nervous system disorders. This emerging field is driven by the anatomical advantages of the nasal route, enabling the direct transport of drugs from the nasal cavity to the brain, thereby circumventing the blood-brain barrier. This review highlights the significance of the anatomical features of the nasal cavity, emphasizing its high permeability and rich blood supply that facilitate rapid drug absorption and onset of action, rendering it a promising domain for neurological therapeutics. Exploring recent developments and innovations in different nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, nanoemulsions, nanosuspensions, carbon nanotubes, mesoporous silica nanoparticles, and nanogels unveils their diverse functions in improving drug-delivery efficiency and targeting specificity within this system. To minimize the potential risk of nanoparticle-induced toxicity in the nasal mucosa, this article also delves into the latest advancements in the formulation strategies commonly involving surface modifications, incorporating cutting-edge materials, the adjustment of particle properties, and the development of novel formulations to improve drug stability, release kinetics, and targeting specificity. These approaches aim to enhance drug absorption while minimizing adverse effects. These strategies hold the potential to catalyze the advancement of safer and more efficient nose-to-brain drug-delivery systems, consequently revolutionizing treatments for neurological disorders. This review provides a valuable resource for researchers, clinicians, and pharmaceutical-industry professionals seeking to advance the development of effective and safe therapies for central nervous system disorders.

State-of-All-the-Art and Prospective Hydrogel-Based Transdermal Drug Delivery Systems

Over the past few decades, notable advancements have been made in the field of transdermal drug delivery systems (TDDSs), presenting a promising alternative to conventional oral drug administration. This comprehensive review aims to enhance understanding of this method by examining various transdermal techniques, the skin’s role as a barrier to TDDS, factors affecting skin diffusion, and current challenges in TDDSs. The primary focus of this analysis centers on TDDSs utilizing hydrogels. A thorough exploration of hydrogel fundamentals, encompassing structure, properties, and synthesis, is provided to underscore the importance of hydrogels as carriers in transdermal drug delivery. The concluding section delves into strategies for hydrogel-based drug delivery, addressing challenges and exploring future directions.

Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders

The lack of effective treatments for neurodegenerative diseases (NDs) is an important current concern. Lipid nanoparticles can deliver innovative combinations of active molecules to target the various mechanisms of neurodegeneration. A significant challenge in delivering drugs to the brain for ND treatment is associated with the blood–brain barrier, which limits the effectiveness of conventional drug administration. Current strategies utilizing lipid nanoparticles and cell-penetrating peptides, characterized by various uptake mechanisms, have the potential to extend the residence time and bioavailability of encapsulated drugs. Additionally, bioactive molecules with neurotropic or neuroprotective properties can be delivered to potentially mediate the ND targeting pathways, e.g., neurotrophin deficiency, impaired lipid metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, accumulation of misfolded proteins or peptide fragments, toxic protein aggregates, oxidative stress damage, and neuroinflammation. This review discusses recent advancements in lipid nanoparticles and CPPs in view of the integration of these two approaches into nanomedicine development and dual-targeted nanoparticulate systems for brain delivery in neurodegenerative disorders.

Fabrication of hydrogel mini-capsules as carrier systems

Conventional drug administration often results in systemic action, thus needing high dosages and leading to potentially pronounced side effects. Targeted delivery, employing carriers like nanoparticles, aims to release drugs at a target site, but only a small fraction of nanoparticles actually reaches it. Microrobots have been proposed to overcome this issue since they can be guided to hard-to-reach sites and locally deliver payloads. To enhance their functionality, we propose microrobots made as deformable capsules with hydrogel shells and aqueous cores, having the potential added advantages of biocompatibility, permeability, and stimulus-responsiveness. In this study, we present a cost-effective method for fabricating core-shell structures without the use of organic solvents or surfactants. The process begins with the dripping of a mixture of hydrogels, agarose and alginate, into a solution to gelate the drops into beads. After they are loaded with calcium ions at different concentrations, they are immersed in an alginate solution to form the shell. Finally, the beads are heated to let the agarose melt and diffuse out, leaving a liquid core. By varying the concentration of calcium ions, we obtain shells of different thickness. To estimate it, we have developed a method using the colour intensity from microscope images. This allowed us to observe that lowering the calcium ions concentration below a threshold does not lead to the formation of continuous shells. For higher concentrations, although the core may remain partially gelled, continuous shells successfully form. Therefore, our fabrication process could find applications in drug delivery, encapsulation systems, and microrobotics.

Individually Tailored Modular "Egg" Hydrogels Capable of Spatiotemporally Controlled Drug Release for Spinal Cord Injury Repair.

Controllable drug delivery systems (DDS) can overcome the disadvantages of conventional drug administration processes, such as high dosages or repeated administration. Herein, we deploy a smart DDS collagen hydrogel for spinal cord injury (SCI) repair based on modular designing of "egg" nanoparticles (NPs) that ingeniously accomplish controlled drug release via inducing a signaling cascade in response to external and internal stimuli. The "egg" NPs consist of a three-layered structure: tannic acid/Fe3+ /tetradecanol "eggshell," zeolitic imidazolate framework-8 (ZIF-8) "egg white," and paclitaxel "yolk". Then NPs served as a crosslinking epicenter, blending with collagen solutions to generate functional hydrogels. Remarkably, the "eggshell" efficiently converts near-infrared (NIR) irradiation into heat. Subsequently, tetradecanol can be triggered to disintegrate via heat, exposing the structure of ZIF-8. The Zn-imidazolium ion coordination bond of the "egg white" was susceptible to cleaving at the acidic SCI site, decomposing the skeleton to release paclitaxel on demand. As expected, the paclitaxel release rate upon NIR irradiation increased up to 3-folds on the seventh day, which matches endogenous neural stem/progenitor cell migration process. Taken together, the collagen hydrogels facilitated the neurogenesis and motor function recovery, demonstrating a revolutionary strategy for spatiotemporally controlled drug release and providing guidelines for the design of DDS. This article is protected by copyright. All rights reserved.

A computational study of droplet-spray formation from pressurized metered dose inhalers with applications to drug deposition in a human lung-airway model

Orally administered drugs using portable devices, such as pressurized metered dose inhalers (pMDIs), can alleviate the symptoms of various respiratory diseases. The basic non-isothermal fluid-particle dynamics of pMDIs have been simulated, including computer model validations and different inhalation techniques, using the Ventolin HFA from GlaxoSmithKline (UK) as a representative application. Specifically, the evolution of thermal droplet sprays has been realistically simulated and experimentally validated, employing the open-source computational fluid dynamics (CFD) toolbox OpenFOAM. The segmental droplet temperature results show elevated temperatures for higher inhalation flow rates because of stronger convective flow around the evaporating droplets. The general problems of high, wasteful oropharyngeal deposition and cold impacting droplets were tackled by devising a new ‘pulsed injection’ strategy in which the spray was broken into pulses with a time delay between them. This new methodology indicated up to a 20% increase in useful lung deposition beyond the oropharynx over conventional drug administration methods. In addition, compared to the conventional single injection approach, the segmental variations in temperature of the deposited aerosols show an increase in temperature of around 10% and 7% for the 30 LPM and 60 LPM cases up to segment 4 for pulsed injection. An increase of 23% and 13% for the 30 LPM and 60 LPM cases were observed for segments 5–7 for pulsed injection. Also, a reduction in inertia of the droplets at 30 LPM, where the spray was broken into eight pulses with 100 ms delay between them, resulted in higher residence times and an increase in temperature of over 35°C.Copyright © 2023 American Association for Aerosol Research

Floating Tablet for Drug Delivery System

The purpose of developing novel delivery systems was to address some issues with the physicochemical properties of pharmaceutical compounds as well as formulation creation, as well as some flaws in conventional dosage forms. The controlled release floating system is a way of medication administration that shows promise. Device for dispensing a potential drug with a narrowing window of absorption. Medicines are insoluble or just very slightly soluble, as well as those that release locally in the stomach and have a low rate of absorption in the colon. Under the floating drug delivery system is a continuous supply gastroretentive medicine administration system. minimally soluble medications are delivered to the absorption site in a controlled manner. These points discuss the floating drug delivery system's advantages and disadvantages in comparison to more conventional drug administration technique. The floating medication delivery system is covered in great length in the review, along with its benefits and drawbacks compared to more traditional drug administration methods.These considerations must be examined when developing dosage forms. There are numerous ways that this dosage type was developed. The review's primary objectives were the formulation and evaluation of the effervescent floating medication delivery system. The goal of this comprehensive study is to bring together the ongoing research on this delivery method, which highlights the different effects that can affect and lessen stomach retention and offers crucial information on its formulation.

Revolutionizing Drugs Administration: Techniques in Drug Delivery and Development

The safety, compliance, and therapeutic efficacy of pharmaceuticals have been greatly improved in the last few years by notable developments in the drug development and administration fields. An overview of significant advances and approaches affecting medication development and distribution is given in this abstract. The administration of pharmacological chemicals to humans and animals for therapeutic purposes is known as drug delivery, and it is a primary area of concern. The safety-to-efficacy ratio of approved drugs has been investigated using a variety of strategies, including dose titration, therapeutic drug monitoring, and personalized drug therapy. Furthermore, a lot of emphasis has been paid to innovative drug delivery techniques such controlled drug release, sustained release, and targeted delivery. Even while conventional drug administration methods are still widely used, these innovations seek to overcome some of its shortcomings. Up to forty percent of pharmaceutical items on the US market are expected to use these cutting-edge techniques by 2000. The efficient transportation of therapeutic agents or naturally derived active compounds to their intended locations for the treatment of various illnesses has been made possible by recent advancements in delivery systems. In order to precisely convey pharmaceuticals to their targeted areas, whether it be a specific location or for the regulated release of medicinal compounds, state-of-the-art technologies must be created. Although various drug delivery strategies have showed promise, obstacles still need to be overcome.

Synthesis and Characterization of Curcumin-Loaded Nanoparticles of Poly(Glycerol Sebacate): A Novel Highly Stable Anticancer System.

The research for alternative administration methods for anticancer drugs, towards enhanced effectiveness and selectivity, represents a major challenge for the scientific community. In the last decade, polymeric nanostructured delivery systems represented a promising alternative to conventional drug administration since they ensure secure transport to the selected target, providing active compounds protection against elimination, while minimizing drug toxicity to non-target cells. In the present research, poly(glycerol sebacate), a biocompatible polymer, was synthesized and then nanostructured to allow curcumin encapsulation, a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of Curcuma longa L. Curcumin was selected as an anticancer agent in virtue of its strong chemotherapeutic activity against different cancer types combined with good cytocompatibility within healthy cells. Despite its strong and fascinating biological activity, its possible exploitation as a novel chemotherapeutic has been hampered by its low water solubility, which results in poor absorption and low bioavailability upon oral administration. Hence, its encapsulation within nanoparticles may overcome such issues. Nanoparticles obtained through nanoprecipitation, an easy and scalable technique, were characterized in terms of size and stability over time using dynamic light scattering and transmission electron microscopy, confirming their nanosized dimensions and spherical shape. Finally, biological investigation demonstrated an enhanced cytotoxic effect of curcumin-loaded PGS-NPs on human cervical cancer cells compared to free curcumin.

Efficacy and Safety of Nanoadministration in the Treatment of Non-Small-Cell Lung Cancer Is Good to Some Extent: A Systematic Review and Meta-Analysis.

Purpose The purpose of this study was to evaluate the efficacy and safety of a nanodrug delivery regimen compared with conventional drug administration for the treatment of lung cancer. Materials and Methods Studies were retrieved through PubMed, Web of Science, and ScienceDirect. Primary and secondary outcome measures, including overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events, were extracted from the retrieved literature and systematically evaluated. Results Six trials, including 4806 advanced non-small-cell lung cancer patients, were included in this study. Compared with conventional drug administration in the treatment of lung cancer, the nanodrug delivery regimen improved the ORR (risk ratio = 1.43, 95% confidence interval (CI) = 1.25–1.63, p ≤ 0.001), prolonged PFS (hazard ratio (HR) = 0.83, 95% CI = 0.76–0.92, p ≤ 0.001), and obtained superior OS (HR = 0.91, 95% CI = 0.83–0.99, p ≤ 0.001). Regarding safety, the incidence of neutropenia, alopecia, sensory neuropathy, myalgia, and arthralgia was lower in the nanoadministration group, but the risk of thrombocytopenia, anaemia, and nausea was increased. Conclusion Nanodrug administration is safe and effective in patients with non-small-cell lung cancer to some extent.

Recent Development of Drug Delivery Systems through Microfluidics: From Synthesis to Evaluation.

Conventional drug administration usually faces the problems of degradation and rapid excretion when crossing many biological barriers, leading to only a small amount of drugs arriving at pathological sites. Therapeutic drugs delivered by drug delivery systems to the target sites in a controlled manner greatly enhance drug efficacy, bioavailability, and pharmacokinetics with minimal side effects. Due to the distinct advantages of microfluidic techniques, microfluidic setups provide a powerful tool for controlled synthesis of drug delivery systems, precisely controlled drug release, and real-time observation of drug delivery to the desired location at the desired rate. In this review, we present an overview of recent advances in the preparation of nano drug delivery systems and carrier-free drug delivery microfluidic systems, as well as the construction of in vitro models on-a-chip for drug efficiency evaluation of drug delivery systems. We firstly introduce the synthesis of nano drug delivery systems, including liposomes, polymers, and inorganic compounds, followed by detailed descriptions of the carrier-free drug delivery system, including micro-reservoir and microneedle drug delivery systems. Finally, we discuss in vitro models developed on microfluidic devices for the evaluation of drug delivery systems, such as the blood–brain barrier model, vascular model, small intestine model, and so on. The opportunities and challenges of the applications of microfluidic platforms in drug delivery systems, as well as their clinical applications, are also discussed.

The effects of glycols on molecular mobility, structure, and permeability in stratum corneum

The skin provides an attractive alternative to the conventional drug administration routes. Still, it comes with challenges as the upper layer of the skin, the stratum corneum (SC), provides an efficient barrier against permeation of most compounds. One way to overcome the skin barrier is to apply chemical permeation enhancers, which can modify the SC structure. In this paper, we investigated the molecular effect of three different types of glycols in SC: dipropylene glycol (diPG), propylene glycol (PG), and butylene glycol (BG). The aim is to understand how these molecules influence the molecular mobility and structure of the SC components, and to relate the molecular effects to the efficiency of these molecules as permeation enhancers. We used complementary experimental techniques, including natural abundance 13C NMR spectroscopy and wide-angle X-ray diffraction to characterize the molecular consequences of these compounds at different doses in SC at 97% RH humidity and 32 °C. In addition, we study the permeation enhancing effects of the same glycols in comparable conditions using Raman spectroscopy. Based on the results from NMR, we conclude that all three glycols cause increased mobility in SC lipids, and that the addition of glycols has an effect on the keratin filaments in similar manner as Natural Moisturizing Factor (NMF). The highest mobility of both lipids and amino acids can be reached with BG, which is followed by PG. It is also shown that one reaches an apparent saturation level for all three chemicals in SC, after which increased addition of the compound does not lead to further increase in the mobility of SC lipids or protein components. The examination with Raman mapping show that BG and PG give a significant permeation enhancement as compared to SC without any added glycol at corresponding conditions. Finally, we observe a non-monotonic response in permeation enhancement with respect to the concentration of glycols, where the highest concentration does not give the highest permeation. This is explained by the dehydration effects at highest glycol concentrations. In summary, we find a good correlation between the molecular effects of glycols on the SC lipid and protein mobility, and macroscopic permeation enhances of the same molecules.

Chitosan Nanoparticle-Based System: A New Insight into the Promising Controlled Release System for Lung Cancer Treatment.

Lung cancer has been recognized as one of the most often diagnosed and perhaps most lethal cancer diseases worldwide. Conventional chemotherapy for lung cancer-related diseases has bumped into various limitations and challenges, including non-targeted drug delivery, short drug retention period, low therapeutic efficacy, and multidrug resistance (MDR). Chitosan (CS), a natural polymer derived from deacetylation of chitin, and comprised of arbitrarily distributed β-(1-4)-linked d-glucosamine (deacetylated unit) and N-acetyl-d-glucosamine (acetylated unit) that exhibits magnificent characteristics, including being mucoadhesive, biodegradable, and biocompatible, has emerged as an essential element for the development of a nano-particulate delivery vehicle. Additionally, the flexibility of CS structure due to the free protonable amino groups in the CS backbone has made it easy for the modification and functionalization of CS to be developed into a nanoparticle system with high adaptability in lung cancer treatment. In this review, the current state of chitosan nanoparticle (CNP) systems, including the advantages, challenges, and opportunities, will be discussed, followed by drug release mechanisms and mathematical kinetic models. Subsequently, various modification routes of CNP for improved and enhanced therapeutic efficacy, as well as other restrictions of conventional drug administration for lung cancer treatment, are covered.

Transdermal Patches: A review of a new drug delivery system approach

Background: Transdermal patch is a transdermal delivery system that can overcome problems in conventional drug administration such as oral drug administration. Patches can provide controlled drug release and have advantages over oral administration such as avoiding first pass metabolism, increasing drug bioavailability, avoiding adverse effects on the gastrointestinal (GI) tract, minimizing patient variability, maintaining a constant drug in plasma, and providing a stable therapeutic effect. The effectiveness of a patch is determined by the ability of the drug to release from the patch matrix and penetrate into the stratum corneum. According to the method used to make the patches, they are divided into single layer, multi-layer, reservoir system, and matrix system patches. The basic components of a patch are polymer matrix, membrane, drug, permeation enhancer, pressure-sensitive adhesives, backing film, release liner, and plasticizer. Methods of review : This review refers to several previously published data regarding physical characteristics and transdermal drug release. This review also includes some explanations regarding the patch as a transdermal drug delivery system. Conclusion: This review focuses on patch analysis methods after the manufacturing process such as physical characteristics test, in vitro drug release test, in vitro skin permeation test, skin irritation test, and stability test as well as some explanations related to transdermal drug delivery system.

Nanotechnology as a tool to advance research and treatment of non-oncologic urogenital diseases.

Nanotechnology represents an expanding area of research and innovation in almost every field of science, including Medicine, where nanomaterial-based products have been developed for diagnostic and therapeutic applications. Because of their small, nanoscale size, these materials exhibit unique physical and chemical properties that differ from those of each component when considered in bulk. In Nanomedicine, there is an increasing interest in harnessing these unique properties to engineer nanocarriers for the delivery of therapeutic agents. Nano-based drug delivery platforms have many advantages over conventional drug administration routes as this technology allows for local and transdermal applications of therapeutics that can bypass the first-pass metabolism, improves drug efficacy through encapsulation of hydrophobic drugs, and allows for a sustained and controlled release of encapsulated agents. In Urology, nano-based drug delivery platforms have been extensively investigated and implemented for cancer treatment. However, there is also great potential for use of nanotechnology to treat non-oncologic urogenital diseases. We provide an update on research that is paving the way for clinical translation of nanotechnology in the areas of erectile dysfunction (ED), overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and catheter-associated urinary tract infections (CAUTIs). Overall, preclinical and clinical studies have proven the utility of nanomaterials both as vehicles for transdermal and intravesical delivery of therapeutic agents and for urinary catheter formulation with antimicrobial agents to treat non-oncologic urogenital diseases. Although clinical translation will be dependent on overcoming regulatory challenges, it is inevitable before there is universal adoption of this technology to treat non-oncologic urogenital diseases.

Designing nanocarriers to overcome the limitations in conventional drug administration for Parkinson's disease.

Designing nanocarriers to overcome the limitations in conventional drug administration for Parkinson's disease.

A Review on Nanoparticles: Preparation and Characterization of Nanoparticles

The development of innovative medication delivery systems has increased at an exponential rate in the last few years. Nanoparticles are particles with a size of between one and one hundred nanometers. Nanoparticles provide substantial benefits over conventional drug administration in terms of high bioavailability, high stability, high drug-carrying capacity, and other characteristics. This review concentrated mostly on the classification of nanoparticles, the technique of synthesis, the evaluation of nanoparticles, and the list of FDA-approved nanomedicines now available on the market.

Microfluidics Technology for the Design and Formulation of Nanomedicines.

In conventional drug administration, drug molecules cross multiple biological barriers, distribute randomly in the tissues, and can release insufficient concentrations at the desired pathological site. Controlling the delivery of the molecules can increase the concentration of the drug in the desired location, leading to improved efficacy, and reducing the unwanted effects of the molecules under investigation. Nanoparticles (NPs), have shown a distinctive potential in targeting drugs due to their unique properties, such as large surface area and quantum properties. A variety of NPs have been used over the years for the encapsulation of different drugs and biologics, acting as drug carriers, including lipid-based and polymeric NPs. Applying NP platforms in medicines significantly improves the disease diagnosis and therapy. Several conventional methods have been used for the manufacturing of drug loaded NPs, with conventional manufacturing methods having several limitations, leading to multiple drawbacks, including NPs with large particle size and broad size distribution (high polydispersity index), besides the unreproducible formulation and high batch-to-batch variability. Therefore, new methods such as microfluidics (MFs) need to be investigated more thoroughly. MFs, is a novel manufacturing method that uses microchannels to produce a size-controlled and monodispersed NP formulation. In this review, different formulation methods of polymeric and lipid-based NPs will be discussed, emphasizing the different manufacturing methods and their advantages and limitations and how microfluidics has the capacity to overcome these limitations and improve the role of NPs as an effective drug delivery system.