Drug Delivery Approaches Research Articles

Advancements in Macrophage-Targeted Drug Delivery for Effective Disease Management.

Macrophages play a crucial role in tissue homeostasis and the innate immune system. They perform essential functions such as presenting antigens, regulating cytokines, and responding to inflammation. However, in diseases like cancer, cardiovascular disorders, and autoimmune conditions, macrophages undergo aberrant polarization, which disrupts tissue regulation and impairs their normal behavior. To address these challenges, there has been growing interest in developing customized targeted drug delivery systems specifically designed for macrophage-related functions in different anatomical locations. Nanomedicine, utilizing nanoscale drug systems, offers numerous advantages including improved stability, enhanced pharmacokinetics, controlled release kinetics, and precise temporal drug delivery. These advantages hold significant promise in achieving heightened therapeutic efficacy, specificity, and reduced side effects in drug delivery and treatment approaches. This review aims to explore the roles of macrophages in major diseases and present an overview of current strategies employed in targeted drug delivery to macrophages. Additionally, this article critically evaluates the design of macrophage-targeted delivery systems, highlighting limitations and discussing prospects in this rapidly evolving field. By assessing the strengths and weaknesses of existing approaches, we can identify areas for improvement and refinement in macrophage-targeted drug delivery.

One-dimensional Polymeric Nanocomposites in Drug Delivery Systems

Abstract: Nanocomposites have become a promising approach for drug delivery in the pharmaceutical field due to several benefits and current research development. Polymer nanocomposites (PNCs) are blends of nanomaterials and polymers with at least one-dimensional structure and one component in the sub-100 nm range. By incorporating nanoparticles into the polymer matrix, it is feasible to create a new class of given characteristics. Nano-clay (a type of nanocomposite) is mainly used for the controlled release of therapeutics in various disease conditions. Nanocomposites are promising drug delivery systems due to several advantages, including surface and rheological characteristics. Considering physical and chemical properties, nanocomposites are divided into two different components. Polymer-fabricated nanocomposites are potentially used in multi-particulate systems, which results in a controlled drug release profile with improved mechanical integrity. Nanotechnology-based drug delivery nanocomposites offer an improved half-life, greater biocompatibility, minimum immunogenicity, site-specific targeting, and avoid membrane barriers. Specifically, one-dimensional (1D) nanocomposites show promising responses in theranostics due to improved surface area-to-volume ratios that offer specific targeting, improved encapsulation efficiency, and susceptibility to biomolecules.

Microemulsions, nanoemulsions and emulgels as carriers for antifungal antibiotics.

According to estimates, up to 25% of the world's population has fungal skin diseases, making them the most prevalent infectious disease. Several chemical classes of antifungal drugs are available to treat fungal infections. However, the major challenges of conventional formulations of antifungal drugs include poor pharmacokinetic profiles like solubility, low permeability, side effectsand decreased efficacy. Novel drug delivery is a promising approach for overcoming pharmacokinetic limitations and increasing the effectiveness of antibiotics. In this review, we have shed light on microemulsions, nanoemulsions, and emulgels as novel drug delivery approaches for the topical delivery of antifungal antibiotics. We believe these formulations have potential translational value and could be developed for treating fungal infections in humans.

Trends in Formulation Approaches for Sustained Drug Delivery to the Posterior Segment of the Eye.

The eye, an intricate organ comprising physical and physiological barriers, poses a significant challenge for ophthalmic physicians seeking to treat serious ocular diseases affecting the posterior segment, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Despite extensive efforts, the delivery of therapeutic drugs to the rear part of the eye remains an unresolved issue. This comprehensive review delves into conventional and innovative formulation strategies for drug delivery to the posterior segment of the eye. By utilizing alternative nanoformulation approaches such as liposomes, nanoparticles, and microneedle patches, researchers and clinicians can overcome the limitations of conventional eye drops and achieve more effective drug delivery to the posterior segment of the eye. These innovative strategies offer improved drug penetration, prolonged residence time, and controlled release, enhancing therapeutic outcomes for ocular diseases. Moreover, this article explores recently approved delivery systems that leverage diverse polymer technologies, such as chitosan and hyaluronic acid, to regulate drug-controlled release over an extended period. By offering a comprehensive understanding of the available formulation strategies, this review aims to empower researchers and clinicians in their pursuit of developing highly effective treatments for posterior-segment ocular diseases.

Targeted drug delivery approaches for the management of tumors

The treatment of tumors requires specific and selective drug delivery approaches capable of efficiently eliminating the root cause of oncogenesis. In this context, targeted drug delivery strategies are the preferred choice due to their exceptional recognition of tumor cell biology and their high transfection efficacy within the tumor microenvironment. The emergence of nanoscale techniques has marked significant milestones in the successful management of various types of tumors. The development of targeted delivery approaches for tumor therapeutics has gained momentum over the past few decades. However, in contrast to the plethora of successful pre-clinical studies, only a limited number of passively targeted nanocarriers have been approved for clinical use, and none of the actively targeted nanocarriers have advanced beyond clinical trials. This review delves into the major molecular principles associated with tumorigenesis, including active targeting, passive targeting, and cell-mediated targeting. It also explores the biological barriers (systemic, biological, and cellular) encountered in tumor drug delivery. Moreover, the review examines various tumor-targeted drug delivery systems that have been developed over the past decade. These systems encompass polymeric nanoparticles (micelles, nanoparticles, dendrimers, and polyplexes), lipid-based carriers (solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion), vesicular systems (liposomes, niosomes, aquasomes, and phytosomes), and inorganic nanocarriers (iron oxide nanoparticles, quantum dots, carbon-based nanoparticles, and mesoporous silica nanoparticles), all designed for the alleviation of tumors.

Reassembled Vacuoles for Drug Delivery Carriers Using Yeast Vacuoles for Enhanced Antibacterial Activity.

In this study, we aimed to develop an efficient drug delivery system by reassembling vacuoles isolated from Saccharomyces cerevisiae. Initially, we assessed the impact of vacuolar enzymes on the efficacy of the loaded antibiotic polymyxin B (PMB), by conducting antibacterial activity tests using Shigella flexneri and Salmonella enteritidis. The results showed that vacuolar enzymes inhibited the effectiveness of PMB, highlighting the limitations of using natural vacuoles as drug carriers. To overcome this, we proposed a new drug delivery system called reassembled vacuoles (ReV). ReV particles were created by removing vacuolar enzymes and reassembling the vacuolar membrane through extrusion. ReV demonstrated improved structural stability, a more uniform size, and enhanced PMB release compared to natural vacuoles. Encapsulation efficiency tests revealed high loading efficiency for both normal vacuoles (NorV) and ReV, with over 80% efficiency at concentrations up to 600 μg/mL. The antibacterial activity of PMB-loaded ReV showed comparable results to PMB alone, indicating the potential of ReV as a drug delivery system. In conclusion, reassembled vacuoles offer a promising approach for drug delivery, addressing the limitations of natural vacuoles and providing opportunities for targeted and efficient drug release.

Pharmaceutical nanonization by green supercritical processing: Investigation of Exemestane anti-estrogenic medicine solubility using machine learning

Oral administration is known as the most prevalently-employed approach of drug delivery because of possessing different benefits like simplicity of use, affordability and negligible sterility restrictions. Despite the noteworthy interests of scientists to manufacture oral therapeutic medicines, poor solubility/bioavailability of orally-administered drugs remains a big challenge in recent years. Therefore, various scientists are trying to develop novel techniques to enhance the solubility of orally-administered therapeutic agents. One of the promising ways, which has recently attracted the global attentions is the use of supercritical fluids (SCFs). This technique could overcome the unfavorable/detrimental influences of organic solvents on the environment due to its environmentally-benign characteristics, non-inflammability and low toxicity. In this research, the solubility of Exemestane (EXE) drug is modeled based on two parameters of temperature and pressure. In order to handle the modeling process, the AdaBoost method with three core models of linear regression (LR), K-Nearest Neighbor (KNN) and Gaussian Process (GPR) are considered, which are tuned by AEO method in terms of their hyper-parameters. Based on the evaluations carried out in this research, ADA GPR, ADA KNN, and ADA LR models showed 0.996, 0.991, and 0.925 values in terms of R-square score. Also, in terms of the error rate, the three models ADA GPR, ADA KNN, and ADA LR have an RMSE error equal to 1.3459, 1.8967, and 5.8875, respectively. Based on these facts and some other analyses, the Gaussian process model optimized and boosted with AdaBoost can be accepted as the most accurate model of this research.

Multimodal nanoparticle-containing modified suberoylanilide hydroxamic acid polymer conjugates to mitigate immune dysfunction in severe inflammation.

Excessive immune activation and immunosuppression are opposing factors that contribute to the dysregulated innate and adaptive immune responses seen in severe inflammation and sepsis. Here, a novel analog of the histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA-OH), was incorporated into immunomodulatory poly(lactic acid)-based nanoparticles (iNP-SAHA) by employing a prodrug approach through the covalent modification of poly(lactic-co-glycolic acid) (PLGA) with SAHA-OH. iNP-SAHA formulation allowed for controlled incorporation and delivery of SAHA-OH from iNP-SAHA and treatment led to multimodal biological responses including significant reductions in proinflammatory cytokine secretions and gene expression, while increasing the survival of primary macrophages under lipopolysaccharide (LPS) challenge. Using a lethal LPS-induced endotoxemia mouse model of sepsis, iNP-SAHA administration improved the survival of mice in a dose-dependent manner and tended to improve survival at the lowest doses compared to iNP control. Further, iNP-SAHA reduced the levels of plasma proinflammatory cytokines and chemokines associated with sepsis more significantly than iNP and similarly improved inflammation-induced spleen and liver toxicity as iNP, supporting its potential polypharmacological activity. Collectively, iNP-SAHA offers a potential drug delivery approach to modulate the multifaceted inflammatory responses observed in diseases such as sepsis.

Exploring the potential of transethosomes in therapeutic delivery: A comprehensive review

AbstractThe growing need for innovative drug delivery systems has led to extensive research to address the limitations associated with conventional dosage forms. Lipid nanoparticles have become prominent as frontline nanocarriers for the delivery of drugs and vaccine formulations. However, the pursuit of new materials and modifications to improve lipid nanocarrier properties remains ongoing. In this context, transethosomes have gained attention as a promising solution, offering distinct advantages over traditional formulations. Transethosomes minimize plasma fluctuations, first‐pass metabolism, organ toxicity, and poor bioavailability. This comprehensive review provides an in‐depth exploration of transethosomes, starting with an overview of the impact of formulation components on their properties and effective targeting. This article delves into the production techniques and evaluation properties employed to ensure efficient drug delivery. A significant contribution of this review lies in the analysis of various routes of administration for transethosomes, including transdermal, transvaginal, pulmonary, and ocular delivery, showcasing the versatility of transethosome‐loaded with drugs and their potential to target specific tissues to achieve controlled release. Furthermore, the potential of functionalization and photodynamic therapy approaches to enhance drug delivery efficacy are explored. Overall, this review emphasizes the significant potentiality of transethosomes as a promising drug delivery system addressing the challenges associated with conventional drug delivery approaches.

Chronomodulated drug delivery systems for the treatment of hypertension: An overview

This review paper aims to provide an overview of chronomodulated drug delivery systems for the treatment of hypertension. Hypertension is a chronic medical condition that affects millions of people worldwide, and effective treatment is crucial to prevent complications such as heart disease and stroke. Chronomodulated drug delivery utilises the concept of circadian rhythms to optimise drug efficacy and minimise side effects. The paper examines various chronomodulated drug delivery approaches, including pulsatile, delayed-release, and chronopharmaceutical systems, highlighting their advantages and limitations. Furthermore, the potential future developments in this field are discussed, emphasising the importance of personalised medicine and the integration of wearable technology for real-time monitoring and drug administration. Overall, this review provides valuable insights into the potential of chronomodulated drug delivery systems for improving patient outcomes and minimising side effects. By utilising chronomodulated drug delivery approaches, healthcare professionals can ensure that medications are released at specific times when they are most effective, thereby maximising their therapeutic benefits. Pulsatile drug delivery systems, for example, can mimic the body's natural circadian rhythm, allowing for targeted drug release during periods of peak efficacy. Delayed-release systems, on the other hand, can help reduce side effects by delivering drugs to specific regions of the gastrointestinal tract where they are better tolerated.

PEGylated therapeutics in the clinic.

The covalent attachment of polyethylene glycol (PEG) to therapeutic agents, termed PEGylation, is a well-established and clinically proven drug delivery approach to improve the pharmacokinetics and pharmacodynamics of drugs. Specifically, PEGylation can improve the parent drug's solubility, extend its circulation time, and reduce its immunogenicity, with minimal undesirable properties. PEGylation technology has been applied to various therapeutic modalities including small molecules, aptamers, peptides, and proteins, leading to over 30 PEGylated drugs currently used in the clinic and many investigational PEGylated agents under clinical trials. Here, we summarize the diverse types of PEGylation strategies, the key advantages of PEGylated therapeutics over their parent drugs, and the broad applications and impacts of PEGylation in clinical settings. A particular focus has been given to the size, topology, and functionalities of PEG molecules utilized in clinically used PEGylated drugs, as well as those under clinical trials. An additional section has been dedicated to analyzing some representative PEGylated drugs that were discontinued at different stages of clinical studies. Finally, we critically discuss the current challenges faced in the development and clinical translation of PEGylated agents.

Advances in Pancreatic Cancer Treatment by Nano-Based Drug Delivery Systems.

Pancreatic cancer represents one of the most lethal cancer types worldwide, with a 5-year survival rate of less than 5%. Due to the inability to diagnose it promptly and the lack of efficacy of existing treatments, research and development of innovative therapies and new diagnostics are crucial to increase the survival rate and decrease mortality. Nanomedicine has been gaining importance as an innovative approach for drug delivery and diagnosis, opening new horizons through the implementation of smart nanocarrier systems, which can deliver drugs to the specific tissue or organ at an optimal concentration, enhancing treatment efficacy and reducing systemic toxicity. Varied materials such as lipids, polymers, and inorganic materials have been used to obtain nanoparticles and develop innovative drug delivery systems for pancreatic cancer treatment. In this review, it is discussed the main scientific advances in pancreatic cancer treatment by nano-based drug delivery systems. The advantages and disadvantages of such delivery systems in pancreatic cancer treatment are also addressed. More importantly, the different types of nanocarriers and therapeutic strategies developed so far are scrutinized.

Drug Delivery and Therapy Strategies for Osteoporosis Intervention.

With the advent of the aging society, osteoporosis (OP) risk increases yearly. Currently, the clinical usage of anti-OP drugs is challenged by recurrent side effects and poor patient compliance, regardless of oral, intravenous, or subcutaneous administration. Properly using a drug delivery system or formulation strategy can achieve targeted drug delivery to the bone, diminish side effects, improve bioavailability, and prolong the in vivo residence time, thus effectively curing osteoporosis. This review expounds on the pathogenesis of OP and the clinical medicaments used for OP intervention, proposes the design approach for anti-OP drug delivery, emphatically discusses emerging novel anti-OP drug delivery systems, and enumerates anti-OP preparations under clinical investigation. Our findings may contribute to engineering anti-OP drug delivery and OP-targeting therapy.

Electrosprayed Core (Cellulose Acetate)-Shell (Polyvinylpyrrolidone) Nanoparticles for Smart Acetaminophen Delivery.

Smart drug delivery, through which the drug molecules are delivered according to the requests of human biological rhythms or by maximizing drug therapeutic effects, is highly desired in pharmaceutics. Many biomacromolecules have been exploited for this application in the past few decades, both in industry and laboratories. Biphasic release, with an intentional pulsatile release and a following extended release stage, represents a typical smart drug delivery approach, which aims to provide fast therapeutic action and a long time period of effective blood drug concentration to the patients. In this study, based on the use of a well-known biomacromolecule, i.e., cellulose acetate (CA), as the drug (acetaminophen, ATP)-based sustained release carrier, a modified coaxial electrospraying process was developed to fabricate a new kind of core-shell nanoparticle. The nanoparticles were able to furnish a pulsatile release of ATP due to the shell polyvinylpyrrolidone (PVP). The time cost for a release of 30% was 0.32 h, whereas the core-shell particles were able to provide a 30.84-h sustained release of the 90% loaded ATP. The scanning electron microscope and transmission electron microscope results verified in terms of their round surface morphologies and the obvious core-shell double-chamber structures. ATP presented in both the core and shell sections in an amorphous state owing to its fine compatibility with CA and PVP. The controlled release mechanisms of ATP were suggested. The disclosed biomacromolecule-based process-structure-performance relationship can shed light on how to develop new sorts of advanced nano drug delivery systems.

Circumventing Physicochemical Barriers of Cyclometalated Gold(III) Dithiocarbamate Complexes with Protein-Based Nanoparticle Delivery to Enhance Anticancer Activity.

Optimizing the bioavailability of drug candidates is crucial to successful drug development campaigns, especially for metal-derived chemotherapeutic agents. Nanoparticle delivery strategies can be deployed to overcome physicochemical limitations associated with drugs to improve bioavailability, pharmacokinetics, efficacy, and minimize toxicity. Biodegradable albumin nanoconstructs offer pragmatic solutions for drug delivery of metallodrugs with translational benefits in the clinic. In this work, we explored a logical approach to investigate and resolve the physicochemical drawbacks of gold(III) complexes with albumin nanoparticle delivery to improve solubility, enhance intracellular accumulation, circumvent premature deactivation, and enhance anticancer activity. We synthesized and characterized stable gold(III) dithiocarbamate complexes with a variable degree of cyclometalation such as phenylpyridine (C^N) or biphenyl (C^C) Au(III) framework and different alkyl chain lengths. We noted that extended alkyl chain lengths impaired the solubility of these complexes in biological media, thus adversely impacting potency. Encapsulation of these complexes in bovine serum albumin (BSA) reversed solubility limitations and improved cancer cytotoxicity by ∼25-fold. Further speciation and mechanism of action studies demonstrate the stability of the compounds and alteration of mitochondria bioenergetics, respectively. We postulate that this nanodelivery strategy is a relevant approach for translational small-molecule gold drug delivery.

A critical analysis of the vesicular drug delivery system: recent advancements and prospects for the future

Vesicular system drug design has revitalised the efficacy of previous medications by effectively regulating and sustaining their therapeutic action. The objective of this study is to evaluate the feasibility of utilizing pharmaceutical interventions to target novel vesicular drug delivery systems. The objective of innovative medication administration is to minimize adverse effects while ensuring drug efficacy at a predetermined or reasonably consistent level within the body. A novel drug delivery approach is characterized by the controlled release of medication at a predetermined rate, which is determined based on factors such as therapeutic requirements, pharmacological properties, drug characteristics, physiological condition of the organism, and other relevant considerations. At present, there is a lack of medication delivery technologies that effectively achieve the aforementioned objectives while minimizing adverse effects. The utilization of vesicular systems in drug delivery has brought about changes in the understanding and application of diagnosis and therapy across different domains within the biomedical field. The vesicular drug delivery system (VDDS) serves as a means to address the disparity between the theoretical ideal and the presently accessible innovative drug delivery systems, accomplishing this by enclosing active moieties within vesicular structures. Various vesicular drug delivery systems, such as liposomes, niosomes, transferases, pharmacosomes, colloidosomes, herbosomes, sphinosomes, among others, have been developed. This review primarily focuses on the examination of various pharmacological targets, both lipiodal and nonlipoidal, within vesicular systems. Liposomes and niosomes represent innovative drug delivery systems.

Cytotoxic effect of iron oxide nanoparticles functionalized with glucose and conjugated with Coumarin (Fe3O4@Glu-Coumarin NPs) on liver cancer, HepG2, cell line

Liver cancer is a severe and frequent disease that is the 3rd leading cause of cancer related-death, worldwide. The use of magnetic nanoparticles in cancer treatment has gained interest. This work aimed to synthesize novel iron oxide nanoparticles functionalized with Glucose and conjugated with Coumarin (Fe3O4@Glu-Coumarin NPs) and characterize their anticancer effects on liver cancer cells. Physicochemical properties of the nanoparticles (NPs) were characterized by Fourier-Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta potential, Thermogravimetric/ Derivative Thermogravimetric Analysis (TGA/DTG), and Vibrating Sample Magnetometer (VSM) analyses, which confirmed the synthesis, purity, magnetic property, and stability of the NPs. The NPs were in a size range of 29–43 nm and their zeta potential and hydrodynamic size were −15 mV and 290 nm, respectively. The antiproliferative effect of Fe3O4@Glu-Coumarin NPs on HepG2 (liver cancer cell line) and THLE2 (normal hepatocyte cell line) was studied by the MTT assay. Further, apoptosis induction in NPs treated cells was evaluated by flow cytometry and Hoechst staining. According to the results, Fe3O4@Glu-Coumarin NPs had considerably higher cytotoxicity for liver cancer cells than for normal human cells and the 50% inhibitory concentration (IC50) was 121 and 273 µg/mL, respectively. In addition, treating THLE2 cells with Fe3O4@Glu-Coumarin NPs at their IC50 concentration significantly increased the frequency of cell apoptosis, compared with the untreated cells and resulted in the appearance of apoptotic nuclear characteristics. In our opinion, the anticancer feature of Fe3O4@Glu-Coumarin NPs is mainly related to the coumarin molecule and, the synthesized NPs could be used for drug delivery approaches after further study.

Advancements in Nanogels for Enhanced Ocular Drug Delivery: Cutting-Edge Strategies to Overcome Eye Barriers.

Nanomedicine in gel or particle formation holds considerable potential for enhancing passive and active targeting within ocular drug delivery systems. The complex barriers of the eye, exemplified by the intricate network of closely connected tissue structures, pose significant challenges for drug administration. Leveraging the capability of engineered nanomedicine offers a promising approach to enhance drug penetration, particularly through active targeting agents such as protein peptides and aptamers, which facilitate targeted release and heightened bioavailability. Simultaneously, DNA carriers have emerged as a cutting-edge class of active-targeting structures, connecting active targeting agents and illustrating their potential in ocular drug delivery applications. This review aims to consolidate recent findings regarding the optimization of various nanoparticles, i.e., hydrogel-based systems, incorporating both passive and active targeting agents for ocular drug delivery, thereby identifying novel mechanisms and strategies. Furthermore, the review delves into the potential application of DNA nanostructures, exploring their role in the development of targeted drug delivery approaches within the field of ocular therapy.

Current Perspectives on Nanoparticle-based Targeted Drug Delivery Approaches in Breast Cancer Treatment.

Breast cancer is avertible yet one of the most widespread carcinomas globally. Though periodic screening and monitoring have resulted in reduced incidences, the malignancy claims increased death rates across the globe. Due to the non-specific and aggressive nature of available conventional cancer therapeutics, there is a crucial need for better treatment paradigms. Recent advancements in nanotechnology have aided in this by utilizing nanocarriers in targeted drug delivery approaches. Optimized nanoparticles have been used to enhance the circulation time and target the efficacy of conventional therapeutic drugs. Passive targeting comprises surface modulation to avoid drug elimination via a standard body defense system. Active targeting includes chemical interaction with various genes, receptors, and antigens overexpressed during cancer progression. Therefore, the present review recapitulates drug delivery approaches and nanoparticle-based targeting that can potentially overcome the limitations of conventional drug therapies.

Importance of P-gp inhibitors and nanoengineered approaches for effective delivery of anti-retroviral drugs across barriers in HIV management

Importance of P-gp inhibitors and nanoengineered approaches for effective delivery of anti-retroviral drugs across barriers in HIV management