Optimal Drug Delivery Research Articles

Unlocking the Potential of Drug Delivery Systems: A Comprehensive Review of Formulation Strategies and Technologies in the Field of Pharmaceutics

: The creation of innovative drug delivery systems to enhance therapeutic effectiveness, safety, and patient compliance has resulted in considerable developments in pharmaceutics in recent years. The most recent formulation techniques and technologies are reviewed in this article to improve medication distribution and accomplish specific therapeutic goals. : This article thoroughly summarizes the most recent formulation techniques and technologies used to enhance medication delivery and provide specific therapeutic effects. It discusses the variety of medication delivery methods, including nanoparticles, liposomes, micelles, and dendrimers, and explores the application of nanotechnology and biotechnology in drug delivery. Additionally, the paper emphasizes the significance of targeted drug delivery systems and their capacity to cross biological barriers including the blood-brain barrier and tumor microenvironment. : The review also addresses the challenges faced in developing and commercializing drug delivery systems and suggests potential solutions to overcome them. Furthermore, the article emphasizes the role of computational modeling and simulation in designing and optimizing drug delivery systems. : Overall, this review paper offers insightful information for pharmaceutics researchers, scientists, and practitioners that will help in the creation of novel drug delivery systems that improve patient outcomes and quality of life.

Recent Advances in Prodrug Approach over Conventional Drug Therapy

Background: Prodrugs represent a strategically designed category of medicinal compounds aimed at optimizing drug pharmacokinetics. By modifying the pharmacological action of the drug within a prodrug, subsequent enzymatic bioconversion in the human body facilitates the release of the active drug. This strategy has been highly effective, as demonstrated by the substantial number of prodrugs found in commercial pharmaceutical products. Prodrugs have emerged as a recognized strategy for augmenting the physical, chemical, biological, or pharmacokinetic attributes of pharmacologically active molecules in the realm of drug research and development. Objective: This systematic review intended to offer insights into the recent developments in the prodrug approach used in drug research and development, with a focus on highlighting its effectiveness. The objective was to illustrate the diverse applications of prodrugs and their impact on enhancing drug properties and therapeutic outcomes. Area covered: This review is centered on the most recent developments in the prodrug approach used for drug development and research. The prodrug concept has a wide range of practical uses, some of which are illustrated in this review article. These illustrations are categorized based on the intention behind their creation. Results: Prodrugs have been designed to address challenges, such as poor water solubility and low bioavailability. Strategies, like using neutral or charged promoieties, have been reported to be successful in enhancing solubility. For permeability and bioavailability, prodrugs have been employed to mask polar groups, enabling better absorption. Prolonged half-life prodrugs have been developed to extend drug action, while tissue-targeted delivery prodrugs have shown promise in enhancing drug delivery to specific sites. Conclusion: Prodrug design offers promising strategies to optimize drug delivery and efficacy. Despite challenges, ongoing clinical trials and research efforts indicate the potential of prodrugs in improving therapeutic outcomes. Addressing formulation challenges and understanding pharmacokinetic variability are essential for successful prodrug development.

A Pioneer Review on Intermolecular Hydrogen Bonding in Drug-Polymer Mixtures: Implication of a Stable Delivery System

Intermolecular hydrogen bonding plays a pivotal role in the stability and efficacy of drug-polymer mixtures, which are essential components in modern drug delivery systems. The knowledge of prominent interactions might provide a means to optimize the physiochemical stability of the developed targeted system. Hence, this review explores the fundamental principles of hydrogen bonding in drug-polymer interactions which can significantly influence the solubility, stability and release profiles of pharmaceutical formulations. The review provides an in-depth examination of the types of functional groups that participate in hydrogen bonding, the characterization techniques employed to study these interactions and the implications of hydrogen bonding on drug delivery. Case studies of successful drug-polymer systems stabilized by hydrogen bonding are presented, highlighting the practical applications and challenges associated with these formulations. Furthermore, the review discusses the future perspectives in this field, including the design of novel polymers and the integration of computational modeling to predict hydrogen bonding behavior. By understanding and leveraging hydrogen bonding, researchers can optimize drug delivery systems, ensuring enhanced bioavailability, controlled release and improved patient outcomes. This review aims to serve as a comprehensive resource for pharmaceutical scientists and formulators, offering insights into the strategic use of hydrogen bonding to develop more effective and stable drug delivery systems.

Impact of dimensional variability of primary packaging materials on the break-loose and gliding forces of prefilled syringes.

A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGF) required during injection, certain primary packaging materials (PPM) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory defined silicone oil quantities in certain drug products, such as ophthalmic, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of PPM has an important role in controlling BLGF. The dimensions of PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmic focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of PPM on the BLGF in ophthalmic PFS. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated, were first sampled during aseptic production, and tested for BLGF. Subsequently, defined dimensions of PPM were measured individually. The results showed that the dimensional variability of PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPM is improvable for critical drug products such as ophthalmic. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.

Pharmacological Approaches to Hearing Loss.

Hearing disorders pose significant challenges to individuals experiencing them and their overall quality of life, emphasizing the critical need for advanced pharmacological approaches to address these conditions. Current treatment options often focus on amplification devices, cochlear implants, or other rehabilitative therapies, leaving a substantial gap regarding effective pharmacological interventions. Advancements in our understanding of the molecular and cellular mechanisms involved in hearing disorders induced by noise, aging, and ototoxicity have opened new avenues for drug development, some of which have led to numerous clinical trials, with promising results. The development of optimal drug delivery solutions in animals and humans can also enhance the targeted delivery of medications to the ear. Moreover, large genome studies contributing to a genetic understanding of hearing loss in humans combined with advanced molecular technologies in animal studies have shown a great potential to increase our understanding of the etiologies of hearing loss. The auditory system exhibits circadian rhythms and temporal variations in its physiology, its vulnerability to auditory insults, and its responsiveness to drug treatments. The cochlear clock rhythms are under the control of the glucocorticoid system, and preclinical evidence suggests that the risk/benefit profile of hearing disorder treatments using chronopharmacological approaches would be beneficial. If translatable to the bedside, such approaches may improve the outcome of clinical trials. Ongoing research into the molecular and genetic basis of auditory disorders, coupled with advancements in drug formulation and delivery as well as optimized timing of drug administration, holds great promise of more effective treatments. SIGNIFICANCE STATEMENT: Hearing disorders pose significant challenges to individuals and their overall quality of life, emphasizing the critical need for advanced pharmacological approaches to address these conditions. Ongoing research into the molecular and genetic basis of auditory disorders, coupled with advancements in drug delivery procedures and optimized timing of drug administration, holds the promise of more effective treatments.

Design optimization of Fucoidan-coating Cationic Liposomes for enhance Gemcitabine delivery.

Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.

Oral in vivo biodistribution of fluorescent labelled nano lipid carrier system of erlotinib using real time optical imaging technique

This study investigates the biodistribution of a nano lipid carrier system (NLCs) containing the hydrophobic drug erlotinib (ERL-NLCs). The system was labelled with the fluorescent dye IR-780 for real-time dynamic imaging. ERL-NLCs were initially developed using the ultrasonication method with oleic acid and stearic acid. In vitro and ex vivo studies were performed to confirm the formation and penetration of NLCs within the intestine. Subsequently, the biological distribution of ERL-NLCs was monitored using a fluorescent dye through the IVIS® fluorescent optical imaging technique in whole live animals. Mice were orally administered blank IR 780 dye solution, ERL suspension, and IR 780 labelled NLCs. Fluorescence images were acquired at different time intervals up to 24 h and then total radiant efficiency was calculated through the region of interest (ROI) of the whole animal at each interval of time for all three groups. To validate the results obtained from in vivo imaging, various organs including lungs, heart, liver, both kidneys, stomach, and intestine were subsequently extracted and examined after 24 h. The ROI was found to be higher in the blank IR 780 dye solution, followed by the drug suspension and IR 780 labelled NLCs. These results confirm that the plain ERL suspension distributes across the body, and its encapsulation in NLCs facilitates passage through the lymphatic intestinal pathway, effectively avoiding first-pass metabolism. The remarkable results indicated that the NLCs formulation effectively circumvents first-pass metabolism by adopting the intestinal lymphatic pathway, thereby enhancing the oral bioavailability of the drug. This observed behaviour underscores the potential of NLCs in optimizing drug delivery and minimizing adverse effects associated with gastrointestinal and metabolic processes.

Enhancing targeted tumor treatment: A novel fuzzy logic framework for precision drug delivery strategy selection

Objective:This study aims to address the challenge of selecting optimal drug delivery strategies for tumor patients by introducing a novel theoretical framework. Methods:We propose a fuzzy logic-based framework for quantitatively assessing Health States (HS) in tumor patients. This framework integrates quantified HS assessments with causality strength analyses, offering a comprehensive understanding of various drug delivery schemes’ effectiveness from pharmacokinetic and pharmacodynamic perspectives. Results:The efficacy of our approach is demonstrated through a series of real-world patient case studies, highlighting its potential to enhance the evaluation and selection of targeted drug delivery strategies. Conclusion:Our work contributes to the field by showcasing practical applications of fuzzy logic in targeted drug delivery systems (TDDs) and establishing a new benchmark for precision in drug delivery strategy selection. Significance:This study has significant implications for developing personalized medical treatments, potentially revolutionizing the field with a more nuanced and scientifically rigorous method for evaluating and selecting drug delivery protocols. Contributions:Development of a fuzzy logic framework for precise quantification of health states in tumor patients. Innovative integration of a causal system for comprehensively evaluating targeted drug delivery strategies.

Revolutionizing Brain Drug Delivery: Buccal Transferosomes on the Verge of a Breakthrough.

The buccal cavity, also known as the oral cavity, is a complex anatomical structure that plays a crucial role in various physiological processes. It serves as a gateway to the digestive system and facilitates the initial stages of food digestion and absorption. However, its significance extends beyond mere digestion as it presents a promising route for drug delivery, particularly to the brain. Transferosomes are lipid-based vesicles that have gained significant attention in the field of drug delivery due to their unique structure and properties. These vesicles are composed of phospholipids that form bilayer structures capable of encapsulating both hydrophilic and lipophilic drugs. Strategies for the development of buccal transferosomes for brain delivery have emerged as promising avenues for pharmaceutical research. This review aims to explore the various approaches and challenges associated with harnessing the potential of buccal transferosomes as a means of enhancing drug delivery to the brain. By understanding the structure and function of both buccal tissue and transferosomes, researchers can develop effective formulation methods and characterization techniques to optimize drug delivery. Furthermore, strategic approaches and success stories in buccal transferosome development are highlighted, showcasing inspiring examples that demonstrate their potential to revolutionize brain delivery.

Developing Self-Nanoemulsifying Drug Delivery Systems Comprising an Artemether-Lumefantrine Fixed-Dose Combination to Treat Malaria.

Despite attempts to control malaria, poor drug bioavailability means malaria still places enormous pressure on health globally. It has been found that the solubility of highly lipophilic compounds can be enhanced through lipid formulations, e.g., self-emulsifying drug delivery systems (SEDDSs). Thus, quality-by-design and characterization were used to justify the development and determine the feasibility of oral oil-in-water SEDDSs comprising a fixed-dose combination (FDC) of artemether-lumefantrine to treat malaria more effectively without the aid of a fatty meal. These formulations were compared to a commercial product containing the same active compounds. Excipient compatibility and spontaneous emulsification capacity of different FDC-excipient combinations were identified by employing isothermal microcalorimetry, solubility, and water titration tests. Pseudoternary phase diagrams were constructed, and checkpoint formulations were selected within the self-emulsification region by reviewing formulation properties essential for optimized drug delivery. SEDDSs capable of enduring phase separation within 24 h were subjected to characterization experiments, i.e., drug concentration determination, cloud point, droplet size, size distribution, self-emulsification time, self-emulsification efficacy, viscosity, zeta potential, and thermodynamic stability analysis. SEDDSs with favorable characteristics were identified in the micro or nano range (SNEDDSs) before being subjected to drug release studies. All final formulations depicted enhanced artemether and lumefantrine release compared to the commercial product, which could not release lumefantrine at a quantifiable concentration in this study. The avocado oil (AVO)4:6 and olive oil (OLV)3:7 SNEDDSs overall portrayed the ideal characteristics and depicted the highest percentage of drug release. This study offers evidence that SNEDDSs from selected natural oils comprising an artemether-lumefantrine FDC can potentially enhance the bioavailability of these lipophilic drugs.

Optimizing Drug Delivery with Nanosuspensions: A Review of Current Strategies

Optimizing Drug Delivery with Nanosuspensions: A Review of Current Strategies

An Insight into Perfusion Anisotropy within Solid Murine Lung Cancer Tumors.

Blood vessels are essential for maintaining tumor growth, progression, and metastasis, yet the tumor vasculature is under a constant state of remodeling. Since the tumor vasculature is an attractive therapeutic target, there is a need to predict the dynamic changes in intratumoral fluid pressure and velocity that occur across the tumor microenvironment (TME). The goal of this study was to obtain insight into perfusion anisotropy within lung tumors. To achieve this goal, we used the perfusion marker Hoechst 33342 and vascular endothelial marker CD31 to stain tumor sections from C57BL/6 mice harboring Lewis lung carcinoma tumors on their flank. Vasculature, capillary diameter, and permeability distribution were extracted at different time points along the tumor growth curve. A computational model was generated by applying a unique modeling approach based on the smeared physical fields (Kojic Transport Model, KTM). KTM predicts spatial and temporal changes in intratumoral pressure and fluid velocity within the growing tumor. Anisotropic perfusion occurs within two domains: capillary and extracellular space. Anisotropy in tumor structure causes the nonuniform distribution of pressure and fluid velocity. These results provide insights regarding local vascular distribution for optimal drug dosing and delivery to better predict distribution and duration of retention within the TME.

Defect-Engineered Metal-Organic Frameworks as Nanocarriers for Pharmacotherapy: Insights into Intracellular Dynamics at The Single Particle Level.

Nanoscale Metal-Organic Frameworks (nanoMOFs) are widely implemented in a host of assays involving drug delivery, biosensing catalysis, and bioimaging. However, the cell pathways and cell fate remain poorly understood. Here, a new fluorescent nanoMOF integrating ATTO 655 into surface defects of colloidal UiO-66 is synthesized, allowing to track the spatiotemporal localization of Single nanoMOF in live cells. Density functional theory reveals the stronger binding of ATTO 655 to the Zr6 cluster nodes compared with phosphate and Alendronate Sodium. Parallelized tracking of the spatiotemporal localization of thousands of nanoMOFs and analysis using machine learning platforms reveals whether nanoMOFs remain outside as well as their cellular internalization pathways. To quantitatively assess their colocalization with endo/lysosomal compartments, a colocalization proxy approach relying on the nanoMOF detection of particles in one channel to the signal in the corresponding endo/lysosomal compartments channel, considering signal versus local background intensity ratio and signal-to-noise ratio is developed. This strategy mitigates colocalization value inflation from high or low signal expression in endo/lysosomal compartments. The results accurately measure the nanoMOFs' colocalization from early to late endosomes and lysosomes and emphasize the importance of understanding their intracellular dynamics based on single-particle tracking for optimal and safe drug delivery.

A multi-scale numerical study of monoclonal antibodies uptake by initial lymphatics after subcutaneous injection

This paper studies the transport of monoclonal antibodies through skin tissue and initial lymphatics, which impacts the pharmacokinetics of monoclonal antibodies. Our model integrates a macroscale representation of the entire skin tissue with a mesoscale model that focuses on the papillary dermis layer. Our results indicate that it takes hours for the drugs to disperse from the injection site to the papillary dermis before entering the initial lymphatics. Additionally, we observe an inhomogeneous drug distribution in the interstitial space of the papillary dermis, with higher drug concentrations near initial lymphatics and lower concentrations near blood capillaries. To validate our model, we compare our numerical simulation results with experimental data, finding a good alignment. Our parametric studies on the drug molecule properties and injection parameters suggest that a higher diffusion coefficient increases the transport and uptake rate while binding slows down these processes. Furthermore, shallower injection depths lead to faster lymphatic uptake, whereas the size of the injection plume has a minor effect on the uptake rate. These findings advance our understanding of drug transport and lymphatic absorption after subcutaneous injection, offering valuable insights for optimizing drug delivery strategies and the design of biotherapeutics.

CFD simulation of blood-mediated drug transport through a dense solid tumour

ABSTRACT Advancements in cancer treatment have underscored the importance of understanding the intricate interplay between tumour microenvironments and drug delivery mechanisms. This research delves into the dynamic relationship between blood-mediated drug transport and the density of the tumour matrix within solid tumours. The study seeks to unravel the effects of varying tumour matrix densities on drug transport characteristics and, subsequently, on the perfusion efficacy of therapeutic agents. Through computational fluid dynamics simulation, this research elucidates the intricate balance between transport dynamics and drug distribution within solid tumours. A simple two-dimensional circular geometry has been chosen to represent the tumour and the surrounding microcirculation. The drug molecules diffuse into the interstitial tumour matrix through the microcirculation and then from the matrix into the tumour cells. The matrix is considered to be a porous medium, and the porosity of the media has been varied to simulate the effect of the matrix density on drug perfusion. Simulation results have shown that the density significantly affects the transport flux of the drug through the tumour matrix. The outcomes of this research hold potential implications for optimising drug delivery strategies in cancer therapy possibly by designing drug molecules that can effectively diffuse through dense tumour matrices.

Role of functional group orientation in the drug partitioning and micelle-mediated delivery of quinoline family drugs to the carrier protein

The understanding of the characteristics of the carrier vehicle and the specific drug it transports is required for designing an effective drug delivery system. We have done a comprehensive analysis of the distribution of three quinolines − quinine, quinidine, and cinchonidine − within hexadecyltrimethyl-ammonium bromide (HTAB) micelles. Further, we tracked their journey as they are transported to the carrier protein human serum albumin (HSA), using spectroscopy, calorimetry, and molecular docking methodologies. The mechanism of partitioning of the quinolines in HTAB micelles is explained based on thermodynamic parameters obtained from isothermal titration calorimetry (ITC). The partitioning coefficient obtained for the quinolines is in the range of 102-104 M−1 and is strongest for quinidine [(1.17 ± 0.78) × 104 M−1]. The stereochemistry and hydroxyl group orientation modulates the partitioning of the quinolines and also the delivery of the quinolines via micellar HTAB. The polar/electrostatic/H-bonding interactions of the hydrophilic polar head of HTAB hinders in efficient quinine delivery, while hydrophobic interactions through the micellar palisade layer facilitate the delivery of quinidine and cinchonidine. Such thorough exploration into the delivery of drugs via micelles is crucial in identifying functionalities necessary to optimize drug delivery systems for the successful delivery of drugs.

Development of Polyvinyl Alcohol (PVA) Nanofibers Containing Cationic Lipid/siRNA Complexes via Electrospinning: The Impact of PVA Characterization.

This study aimed to develop polyvinyl alcohol (PVA) nanofibers encapsulating 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/siRNA complexes via electrospinning for the delivery of nucleic acid-based drugs. It also focused on the influence of the intrinsic properties of PVA on the efficacy of the system. PVA nanofibers, with diameters of 300-400 nm, were obtained, within which the siRNA remained intact and the DOTAP/siRNA complexes were uniformly dispersed. By incorporating DOTAP/siRNA complexes into the PVA nanofibers and assessing the impact of their RNA interference (RNAi) activity in A549-Luc cells, a stable inhibition of luciferase expression was observed. An examination of the nanofiber preparation process revealed that even when DOTAP or siRNA were added separately to the PVA solution without forming complexes, the RNAi effect was retained. The DOTAP/siRNA complexes released from the PVA nanofibers were internalized by the cells, with some PVA residues remaining on their surfaces. The significance of the degree of hydrolysis and polymerization of PVA on the performance of nanofibers was highlighted. Notably, PVA with a low degree of hydrolysis substantially enhanced RNAi effects, with luciferase expression inhibition reaching 91.5 ± 0.7%. Nanofibers made of PVA grades with anionic or cationic modifications were also evaluated, suggesting that they affect the efficacy of siRNA delivery. The insights obtained suggest avenues for future research to optimize drug delivery systems further.

A Pioneering Review on Quantitative Analysis of the Effect of Macromolecular Crowding on Drug Transport and Release: Current Implications

The intricate interplay of macromolecules within biological systems significantly influences the behavior of therapeutic agents, making the understanding of macromolecular crowding crucial for the advancement of drug delivery technologies. This review article provides a comprehensive analysis of the effects of macromolecular crowding on drug transport and release, emphasizing its quantitative impact and current implications in the field. Macromolecular crowding, characterized by the dense packing of proteins, nucleic acids, and other polymers in cellular environments, alters key biophysical properties, such as viscosity, diffusion rates, and molecular interactions. These changes critically affect the pharmacokinetics and pharmacodynamics of drugs, presenting both challenges and opportunities for therapeutic design and application. The article delves into the theoretical foundations of macromolecular crowding, grounded in thermodynamics and statistical mechanics, to elucidate how such conditions modulate drug behavior. Through an integrated review of empirical research and advanced simulation models, it highlights innovative strategies to harness crowding effects for optimizing drug delivery systems. The discussion extends to the evaluation of experimental methodologies and measurement techniques, including spectroscopy and imaging that are pivotal in quantifying the implications of crowding. This pioneering review not only synthesizes current research but also identifies gaps in knowledge and proposes directions for future investigation. It aims to serve as a vital resource for researchers and practitioners, fostering the development of more effective drug delivery mechanisms by leveraging the nuanced understanding of macromolecular crowding. This work underscores the potential of this underexplored area to significantly influence the next generation of pharmaceutical formulations and therapeutic interventions.

Nanocarrier optimization: Encapsulating Hydrastis canadensis in chitosan nanoparticles for enhanced antibacterial and dye degradation performance

This study focuses on the optimization of Hydrastis canadensis-based nanocarriers in environmental and microbial applications like antibacterial and dye degradation. Hydrastis canadensis (H. canadensis) is loaded into the nanocarrier using a gelation method. Characterization involves pH analysis, UV-VIS spectrophotometry, scanning electron microscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, high-performance liquid chromatography, encapsulation efficiency. Further antimicrobial activity against Staphylococcus aureus and Escherichia coli were tested. Dye degradation was evaluated at concentrations of 1 % of high molecular (HM) and 1.5 % of low molecular (LM) chitosan nanoparticles with both 3C and 1000C concentrations of the drug. The obtained results confirm the presence of chitosan nanocarrier alongside the pure drug in 1 % HM and 1.5 % LM chitosan particles with a notable encapsulation efficiency activity in both 3C and 1000C concentrations. Antimicrobial studies were carried out using the agar well diffusion method and revealed a significant zone of inhibition of 20 mm and 25 mm for E. coli and S. aureus, respectively in chitosan nanocarrier-loaded samples compared to pure drug and chitosan nanocarriers samples. The dye degradation studies of four dyes methylene blue, methylene orange, methylene red, and safranin using both pure drugs and chitosan nanocarrier-loaded drugs showed the highest percentage of degradation (76 %) against methylene blue in the chitosan nanocarrier-drug loaded formulation. These findings cumulatively underscore chitosan nanoparticles can be used as an effective carrier for Hydrastis Canadensis, with enhanced antimicrobial and dye degradation capabilities. Varied concentrations and molecular weights highlight the versatility of the ionotropic gelation method in optimizing drug delivery. Enhanced efficacy of the nanocarrier was evident in the observed zone of inhibition in antimicrobial testing. The substantial degradation percentage in methylene blue emphasizes the formulation's applicability in environmental dye removal processes, with potential avenues for improvement explored through interactions between the chitosan nanocarrier and H. canadensis characteristics. Future investigations may focus on scaling up the optimized formulation for large-scale applications and exploring release kinetics and comprehensive toxicity assessments for a holistic understanding of potential environmental and biomedical implications.

Harnessing cholesterol uptake of malaria parasites for therapeutic applications

Parasites, such as the malaria parasite P. falciparum, are critically dependent on host nutrients. Interference with nutrient uptake can lead to parasite death and, therefore, serve as a successful treatment strategy. P. falciparum parasites cannot synthesise cholesterol, and instead source this lipid from the host. Here, we tested whether cholesterol uptake pathways could be ‘hijacked’ for optimal drug delivery to the intracellular parasite. We found that fluorescent cholesterol analogues were delivered from the extracellular environment to the intracellular parasite. We investigated the uptake and inhibitory effects of conjugate compounds, where proven antimalarial drugs (primaquine and artesunate) were attached to steroids that mimic the structure of cholesterol. These conjugated antimalarial drugs improved the inhibitory effects against multiple parasite lifecycle stages, multiple parasite species, and drug-resistant parasites, whilst also lowering the toxicity to human host cells. Steroids with introduced peroxides also displayed antimalarial activity. These results provide a proof-of-concept that cholesterol mimics can be developed as a drug delivery system against apicomplexan parasites with the potential to improve drug efficacy, increase therapeutic index, and defeat drug resistance.