Delivery Paradigm Research Articles

Microorganism microneedle micro-engine depth drug delivery

As a transdermal drug delivery method, microneedles offer minimal invasiveness, painlessness, and precise in-situ treatment. However, current microneedles rely on passive diffusion, leading to uncontrollable drug penetration. To overcome this, we developed a pneumatic microneedle patch that uses live Enterobacter aerogenes as microengines to actively control drug delivery. These microbes generate gas, driving drugs into deeper tissues, with adjustable glucose concentration allowing precise control over the process. Our results showed that this microorganism-powered system increases drug delivery depth by over 200%, reaching up to 1000 μm below the skin. In a psoriasis animal model, the technology effectively delivered calcitriol into subcutaneous tissues, offering rapid symptom relief. This innovation addresses the limitations of conventional microneedles, enhancing drug efficiency, transdermal permeability, and introducing a creative paradigm for on-demand controlled drug delivery.

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Starch-based "smart" nanomicelles: Potential delivery systems for doxorubicin.

Vesicular nanosystems are a cornerstone to the contemporary drug delivery paradigm owing to their ability to encapsulate a variety of drug molecules, which improves the overall pharmacokinetics and bioavailability of the cargo drug. These systems have proven potential in the delivery of hydrophobic chemotherapeutic "Doxorubicin" (DOX), which faces frequent challenge relating to its nonspecific interactions, dose-limiting toxicity (myelosuppression being the most common manifestation), and short half-life (distribution half-life of 5 min, terminal half-life of 20-48 h), which limit its overall clinical effectiveness. "Smart" nanomicelles with stimuli-responsive linkages take advantage of tumor microenvironment for deploying the cargo drug at the target site, which prevents nonspecific distribution and, hence, low toxicity. Similarly, those with stealth properties evade protein response, which triggers the immunogenic response. The nanomicelles co-loaded with magnetic nanoparticles provide additional utility such as contrast enhancement agents in theranostics. Overall, the starch-based nanomicelles prove to be an excellent delivery system for overcoming the limitations associated with the conventional DOX delivery regime.

Ultrasound and x-ray imageable poloxamer-based hydrogel for loco-regional therapy delivery in the liver.

Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances-which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes.

Possible association of dose rate and the development of late visual toxicity for patients with intracranial tumours treated with pencil beam scanned proton therapy

Background and purposeRare but severe toxicities of the optic apparatus have been observed after treatment of intracranial tumours with proton therapy. Some adverse events have occurred at unusually low dose levels and are thus difficult to understand considering dose metrics only. When transitioning from double scattering to pencil beam scanning, little consideration was given to increased dose rates observed with the latter delivery paradigm. We explored if dose rate related metrics could provide additional predicting factors for the development of late visual toxicities.Materials and methodsRadiation-induced intracranial visual pathway lesions were delineated on MRI for all index cases. Voxel-wise maximum dose rate (MDR) was calculated for 2 patients with observed optic nerve toxicities (CTCAE grade 3 and 4), and 6 similar control cases. Additionally, linear energy transfer (LET) related dose enhancing metrics were investigated.ResultsFor the index cases, which developed toxicities at low dose levels (mean, 50 GyRBE), some dose was delivered at higher instantaneous dose rates. While optic structures of non-toxicity cases were exposed to dose rates of up to 1 to 3.2 GyRBE/s, the pre-chiasmatic optic nerves of the 2 toxicity cases were exposed to dose rates above 3.7 GyRBE/s. LET-related metrics were not substantially different between the index and non-toxicity cases.ConclusionsOur observations reveal large variations in instantaneous dose rates experienced by different volumes within our patient cohort, even when considering the same indications and beam arrangement. High dose rate regions are spatially overlapping with the radiation induced toxicity areas in the follow up images. At this point, it is not feasible to establish causality between exposure to high dose rates and the development of late optic apparatus toxicities due to the low incidence of injury.

Design and characterization of 3D-printed hollow microneedle arrays for transdermal insulin delivery

The delivery of insulin to diabetic patients remains a challenge due to the limitations of current insulin delivery paradigms, including painful cannula insertion, potential infections, interference with activity, embarrassment, and sometimes cost. To address this problem, we designed and fabricated nine prototypes of stereolithographic 3D-printed microneedle arrays (MNAs) appropriate for the minimally invasive delivery of insulin. We characterized their transdermal penetration performance by delivering fluid at a constant rate to porcine skin through these MNAs. Moreover, we characterized the force required for these MNAs to puncture porcine skin using a mechanical testing apparatus. We developed an improved method of mechanical testing for the MNAs against porcine skin by incorporating an imitation soft tissue layer under the skin and compared the MNA results with those using a single microneedle and a hypodermic needle. In addition, we investigated the mechanical flexural strength of the MNAs by performing a flexural failure load test on them. We confirmed that the prototype MNAs are mechanically robust and do not fracture during skin penetration, setting the stage for future trials in vitro and in vivo. The final, optimized designs are freely available in stereolithography (STL) file format.

Steps to accelerate net zero delivery

Worley and Princeton University’s Andlinger Center for Energy and the Environment are working together to shift the net zero narrative from what is needed, to how to meet this immense infrastructure delivery challenge. Together, we assert that this challenge cannot be met through a traditional project delivery approach. We have developed a new delivery paradigm, which identifies five key shifts in infrastructure delivery practices to build the durable, responsible, and pragmatic means of achieving the required scale and speed of mid-century net zero. We believe that the new delivery paradigm needs to be in place by 2030, and an annual survey conducted by Princeton University is tracking the uptake by industry. The third instalment in our thought leadership series ‘From Ambition to Reality (FATR): Steps to accelerate net zero delivery’, explores the scale of the EU’s 2030 Hydrogen ambition and how the five key shifts could accelerate the delivery of 10 million tonnes per annum of renewable hydrogen in the next 6 years. This has led to our proposed EU Renewable H2 Plan, which has been further globalised to our 2024 FATR Plan for application to any low carbon sector or supply chain. In this paper, we examine the initiatives set out in the 2024 FATR Plan in the context of the Australian oil and gas industry. We outline the steps that can be taken right now to support the decarbonisation of the Australian oil and gas industry alongside the development of a new hydrogen industry.

National Emergency Tele-Critical Care in a Pandemic: Barriers and Solutions.

The COVID-19 pandemic caused tremendous disruption to the U.S. healthcare system and nearly crippled some hospitals during large patient surges. Limited ICU beds across the country further exacerbated these challenges. Telemedicine, specifically tele-critical care (TCC), can expand a hospital's clinical capabilities through remote expertise and increase capacity by offloading some monitoring to remote teams. Unfortunately, the rapid deployment of telemedicine, especially TCC, is constrained by multiple barriers. In the summer of 2020, to support the National Emergency Tele-Critical Care Network (NETCCN) deployment, more than 50 national leaders in applying telemedicine technologies to critical care assembled to provide their opinions about barriers to NETCCN implementation and strategies to overcome them. Through consensus, these experts developed white papers that formed the basis of this article. Herein, the authors share their experience and propose multiple solutions to barriers presented by laws, local policies and cultures, and individual perspectives according to a minimum, better, best paradigm for TCC delivery in the setting of a national disaster. Cross-state licensure and local privileging of virtual experts were identified as the most significant barriers to rapid deployment of services, whereas refining the model of TCC to achieve the best outcomes and defining the best financial model is the most significant for long-term success. Ultimately, we conclude that a rapidly deployable national telemedicine response system is achievable.

Beyond the Maze: Recent Advancements in Molecular and Cellular Tethered Drug Delivery Systems.

The relentless pursuit of precision medicine has catalyzed the development of molecular and cellular tethered drug delivery systems, a burgeoning field that stands to redefine the paradigms of therapeutic delivery. This review encapsulates the cutting-edge advancements within this domain, emphasizing the engineering of molecular tethers and cellular vectors designed to ferry therapeutics directly to their target sites with unparalleled specificity and efficiency. By exploiting the unique biochemical signatures of disease states, these systems promise a substantial reduction in off-target effects and an enhancement in drug bioavailability, thereby mitigating the systemic side effects that are often associated with conventional drug therapies. Through a synthesis of recent research findings, this review highlights the innovative approaches being explored in the design and application of these tethered systems, ranging from nanotechnology-based solutions to genetically engineered cellular carriers. The potential of these systems to provide targeted therapy for a wide array of diseases, including cancer, autoimmune disorders, and neurological conditions, is thoroughly examined. This abstract aims to provide a succinct overview of the current state and future prospects of molecular and cellular tethered drug delivery systems in advancing the frontiers of precision medicine.

Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury

AbstractSpinal cord injury (SCI) is a cause of profound and irreversible damage, with no effective therapy to promote functional recovery. Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near‐infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI. Dose optimization studies were performed using a serum withdrawal model of injury in cultures of primary adult rat dorsal root ganglion neurons (DRGN). Implantable and transcutaneous PBM delivery protocols were developed and validated using cadaveric modeling. The efficacy of PBM in promoting recovery after SCI in vivo was studied in a dorsal column crush injury model of SCI in adult rats. Optimal neuroprotection in vitro was achieved between 4 and 22 mW/cm2. 11 mW/cm2 for 1 min per day (0.66 J/cm2) increased cell viability by 45% over 5 days (p <0.0001), increasing neurite outgrowth by 25% (p <0.01). A method for invasive application of PBM was developed using a diffusion‐tipped optogenetics fiber optic. Delivery methods for PBM were developed and validated for both invasive (iPBM) and noninvasive (transcutaneous) (tcPBM) application. iPBM and tcPBM (24 mW/cm2 at spinal cord, 1 min per day (1.44 J/cm2) up to 7 days) increased activation of regeneration‐associated protein at 3 days after SCI, increasing GAP43+ axons in DRGN from 18.0% (control) to 41.4% ± 10.5 (iPBM) and 45.8% ± 3.4 (tcPBM) (p <0.05). This corresponded to significant improvements at 6 weeks post‐injury in functional locomotor and sensory function recovery (p <0.01), axonal regeneration (p <0.01), and reduced lesion size (p <0.01). Our results demonstrated that PBM achieved a significant therapeutic benefit after SCI, either using iPBM or tcPBM application and can potentially be developed for clinical use in SCI patients.

Development of QCT loaded TPGS coated solid lipid nanoparticles for improved in vivo neuroprotective activity in LPS administered adult zebrafish model: A QbD-based approach

This work contains the development of QCT-loaded TPGS-coated SLNs by QbD to enhance neuroinflammation potential. Developed SLNs were in the nanometer range (263±3.62 nm) with desired parameters i.e., PDI (0.244±0.003), zeta potential (28.2 ± 0.74 mV), and%EE (74.3 ± 2.45 %) respectively. The release study showed sustained drug release of the developed formulation T-QCT-SLN (83.2 % release in 48 h). The study found QCT can reduce oxidative stress and neuroinflammation in adult zebrafish. Results showed reduced disruption in neuronal cells, decreased TNF-α and IL-1β levels, and reduced LPO, nitrite, and AChEs levels while increasing GSH levels, indicating its potential for treating oxidative stress and neuroinflammation. It can be concluded that QCT-loaded TPGS-coated SLN effectively prevents oxidative damage and neuroinflammation in adult zebrafish exposed to LPS compared to the QCT alone. The suggested work will be a focal paradigm for neuroinflammatory drug delivery.

A Data Mining Study of Zinc Oxide Nanostructures Utilization in Drug Delivery Nanosystems

AbstractThe present investigation offers a thorough bibliometric exploration spotlighting the pivotal utilization of zinc oxide nanostructures, encompassing both zero‐dimensional (0D) nanoparticles and one‐dimensional (1D) nanostructures, within the realm of nanotechnology‐driven drug delivery systems. This analysis particularly illuminates the distinctive potential of these nanostructures in the cancer therapy context, not merely as carriers and deliverers of pharmaceutical agents, but as entities capable of selectively inducing apoptosis in cancer cells through the orchestrated generation of reactive oxygen species (ROS). Recent research endeavors notably underscore the application prospects of ZnO nanostructures in domains like DNA cleavage, bioimaging, and agricultural defense mechanisms. Moreover, the study elucidates the pronounced enhancement in solubility and biocompatibility that these nanostructures bring about when harmoniously integrated into polymeric nanocomposites. Concomitantly, the involvement of polymers in this symbiotic system is unveiled, wherein they play a multifaceted role in dictating release selectivity, thereby facilitating targeted and efficacious interactions with tissues. Functionally engineered polymeric nanocomposites emerge as promising candidates for targeted delivery modalities in cancer treatment, demonstrating an affinity for specific cell receptors and exhibiting enhanced cellular uptake within the size range of 100–200 nm. The study unearths robust associations among pivotal research terminologies through an exhaustive analysis of Link Strength Between Items (LSBI), culminating in the presentation of a cogent map delineating the evolving trends and forthcoming trajectories in this dynamic domain. In summation, this all‐encompassing bibliometric inquiry serves as a poignant testament to the prodigious potential of zinc oxide nanostructures in the realm of forthcoming nanotechnology‐driven drug delivery paradigms.

Integration of UAVs with public transit for delivery: Quantifying system benefits and policy implications

The maturation and scalability of unmanned aerial vehicle (UAV) technology offer transformative opportunities to revolutionize prompt delivery. This study explores integrating UAVs with public transportation vehicles (PTVs) to establish a novel delivery paradigm that enhances revenue for public transit operators and improves transport system efficiency without compromising passenger convenience or operational efficiency. Employing hexagonal planning technology, this study identifies and quantifies the available spatio-temporal resources of PTVs for UAV integration. This involves aligning the spatio-temporal dynamics of prompt delivery orders with PTV ridership, based on field data from Beijing’s Haidian District. Utilizing these outputs, we quantitatively analyze the benefits of integrating UAVs with PTVs on increasing public transit revenue, and potentials of reducing carbon emissions and mitigating congestion. Furthermore, we quantify the long-term benefits of UAV-PTV integration by predicting future increases in delivery demand. Based on obtained quantitative results, this study discusses practical and policy implications to support the sustainable integration of UAVs with PTVs.

Augmented and virtual reality in financial services: A review of emerging applications

In the contemporary financial landscape, the advent of Augmented Reality (AR) and Virtual Reality (VR) technologies heralds a transformative era, redefining the paradigms of customer engagement, service delivery, and educational methodologies within the sector. This paper embarks on a scholarly expedition to dissect the integration of AR and VR technologies in financial services, elucidating their evolutionary trajectory, foundational concepts, and the burgeoning implications of their adoption across various facets of the industry. Anchored by a qualitative research design, the study meticulously navigates through the technological advancements, applications, theoretical frameworks, and the regulatory and security considerations that encapsulate the AR and VR domains within financial services. The investigation reveals a nascent yet rapidly evolving landscape, where AR and VR technologies emerge as potent catalysts for innovation, operational efficiency, and competitive differentiation. The findings underscore the strategic importance of AR and VR in enhancing customer experiences, democratizing financial education, and fostering a culture of continuous innovation and adaptation. Conclusively, the paper articulates pragmatic recommendations for overcoming the multifarious challenges associated with AR and VR integration, advocating for a strategic, informed, and ethical approach to harnessing their transformative potential. This scholarly endeavor not only achieves its aims and objectives with academic rigor but also contributes a seminal perspective to the discourse on digital transformation in financial services, urging stakeholders to transcend traditional paradigms and embrace the digital renaissance heralded by AR and VR technologies.

Distributed multi-horizon model predictive control for network of energy hubs

The increasing penetration of renewable energy resources has transformed the energy system from a traditional hierarchical energy delivery paradigm to a distributed structure. Local energy hubs activates synergies among energy carriers rendering flexibility to the system and gives rise to possible energy trading among networked local energy hubs. Joint operation of such hubs and peer-to-peer trading between them can improve energy efficiency and support the integration of renewable energy resources. However, for such complex systems involving multiple stakeholders, both computational tractability and privacy concerns need to be accounted for. In this work, a novel multi-horizon distributed MPC framework is introduced for the control of energy hub networks. The multi-horizon approach increases the prediction horizon for MPC without compromising the time discretization or making the problem computationally intractable. The distributed scheme is based on a consensus alternating direction method of multipliers algorithm. It combines the superior performance of the centralized approach with the privacy preservation of the decentralized approach. A benchmark three-hub network is used to investigate the performance of the proposed method in simulation and compare it to the decentralized, centralized and standard model predictive control (MPC) approaches. The results show superior performance of the distributed multi-horizon MPC in terms of total cost, computational time, and robustness to demand and prices variations. Finally, the performance was also experimentally validated in real time by implementing the controller on a real energy hub system.

Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors. To improve the solubility and bioavailability of auranofin, we hypothesized that the nanodelivery of auranofin using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance anticancer activity against TNBC by comparing the best nanoformulation with the free drug. The selection of the nanoformulation was based on synthesis of various chitosan PEG copolymers via formaldehyde-mediated engraftment of PEG onto chitosan to form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties of the copolymer was based on the formaldehyde ratio towards nanoparticles (CP 1-4 NPs). Following the recruitment of PEG onto the chitosan polymer surface, we explored how this process influenced the stiffness of the nanoparticle using atomic force microscopy (AFM), a factor crucial for in vitro and in vivo studies. Our objective was to ensure the full functionality and inherent properties of chitosan as the parent polymer was maintained without allowing PEG to overshadow chitosan's unique cationic properties while improving solubility in neutral pH. Hence, CP 2 NP was chosen. To demonstrate the efficacy of CP 2 NP as a good delivery carrier for auranofin, we administered a dose of 3 mg/kg of auranofin, in contrast to free auranofin, which was given at 5 mg/kg. In vivo studies revealed the potency of encapsulated auranofin against TNBC cells with a severe necrotic effect following treatment superior to that of free auranofin. In conclusion, chitosan-g-PEG nanoparticles have the potential to be an excellent delivery system for auranofin, increasing its effectiveness and potentially reducing its clinical limitations.

Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.

Early Stage Preclinical Formulation Strategies to Alter the Pharmacokinetic Profile of Two Small Molecule Therapeutics.

Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. There is a need to develop strategies for achieving the desired systemic concentration for these compounds. This will enable further evaluation of the biological response upon a compound-target interaction, providing deeper insight into the postulated biological pathways. Our study elucidates alternative drug delivery paradigms by comparing formulation strategies across oral (PO), intraperitoneal (IP), subcutaneous (SC), and intravenous (IV) routes. While each modality boasts its own set of merits and constraints, it is the drug's formulation that crucially influences its pharmacokinetic (PK) trajectory and the maintenance of its therapeutic levels. Our examination of model compounds G7883 and G6893 highlighted their distinct physio-chemical attributes. By harnessing varied formulation methods, we sought to fine-tune their PK profiles. PK studies showcased G7883's extended half-life using an SC oil formulation, resulting in a 4.5-fold and 2.5-fold enhancement compared with the IP and PO routes, respectively. In contrast, with G6893, we achieved a prolonged systemic coverage time above the desired target concentration through a different approach using an IV infusion pump. These outcomes underscore the need for tailored formulation strategies, which are dictated by the compound's innate properties, to reach the optimal in vivo systemic concentrations. Prioritizing formulation and delivery optimization early on is pivotal for effective systemic uptake, thereby facilitating a deeper understanding of biological pathways and expediting the overall clinical drug development timeline.

Advancing Drug Delivery Paradigms: Polyvinyl Pyrolidone (PVP)-Based Amorphous Solid Dispersion for Enhanced Physicochemical Properties and Therapeutic Efficacy.

The current challenge in drug development lies in addressing the physicochemical issues that lead to low drug effectiveness. Solubility, a crucial physicochemical parameter, greatly influences various biopharmaceutical aspects of a drug, including dissolution rate, absorption, and bioavailability. Amorphous solid dispersion (ASD) has emerged as a widely explored approach to enhance drug solubility. The objective of this review is to discuss and summarize the development of polyvinylpyrrolidone (PVP)-based amorphous solid dispersion in improving the physicochemical properties of drugs, with a focus on the use of PVP as a novel approach. This review was conducted by examining relevant journals obtained from databases such as Scopus, PubMed, and Google Scholar, since 2018. The inclusion and exclusion criteria were applied to select suitable articles. This study demonstrated the versatility and efficacy of PVP in enhancing the solubility and bioavailability of poorly soluble drugs. Diverse preparation methods, including solvent evaporation, melt quenching, electrospinning, coprecipitation, and ball milling are discussed for the production of ASDs with tailored characteristics. PVP-based ASDs could offer significant advantages in the formulation strategies, stability, and performance of poorly soluble drugs to enhance their overall bioavailability. The diverse methodologies and findings presented in this review will pave the way for further advancements in the development of effective and tailored amorphous solid dispersions.