Route Of Delivery Research Articles

Development of complex generics: Insights into trends, challenges, and market opportunities

Complex generics are generic versions of pharmaceutical products containing formulations, routes of delivery, dosage forms, drug-device combination products, active ingredients in complex form or features that may make it difficult for products to prove bio-equivalency. NBCD (Non-Biological Complex Drugs) offers workable options for approving complicated generics through optimal utilization of USFDA’s current shortened approval processes, 505(j) and 505(b) (2). The FDA awarded funding on August 2020 to establish the Centre for Research on Complex Generics (CRCG) to address issues related to complex generic development. Complex Generics Face Key Challenges such as bioequivalence standards, substitutability, patent/exclusivity issues, and lifecycle quality assurance. PLGA (poly (lactic-co-glycolic acid)) is a preferred inactive ingredient for long-acting injectable medications with complex formulations. Challenges in creating long-acting injectable/implantable (LAI) drug products are drug loading and release issue, physicochemical properties of PLGA etc. To achieve critical “time-to-market” strategic and operational goals, biopharma businesses should implement Good Regulatory Practices by specifying the where, what, when, and how. Biopharma businesses should select industry partners with clinical experience, worldwide regulatory knowledge, and quality/compliance competence to quickly deliver verified results to avoid problems in the shift to complex generics. The complex generics market is poised for significant growth, increasing from $84 billion in 2024 to $170 billion by 2035, at a compound annual growth rate (CAGR) of 8%. In future the complex generics market will evolve through innovative drug delivery methods, personalized treatment approaches, advanced manufacturing techniques, increased biosimilar products, strategic partnerships to address shifting healthcare needs.

Transforming Medicine: Cutting-Edge Applications of Nanoscale Materials in Drug Delivery.

Since their inception in the early 1960s, the development and use of nanoscale materials have progressed tremendously, and their roles in diverse fields ranging from human health to energy and electronics are undeniable. The application of nanotechnology inventions has revolutionized many aspects of everyday life including various medical applications and specifically drug delivery systems, maximizing the therapeutic efficacy of the contained drugs by means of bioavailability enhancement or minimization of adverse effects. In this review, we utilize the CAS Content Collection, a vast repository of scientific information extracted from journal and patent publications, to analyze trends in nanoscience research relevant to drug delivery in an effort to provide a comprehensive and detailed picture of the use of nanotechnology in this field. We examine the publication landscape in the area to provide insights into current knowledge advances and developments. We review the major classes of nanosized drug delivery systems, their delivery routes, and targeted diseases. We outline the most discussed concepts and assess the advantages of various nanocarriers. The objective of this review is to provide a broad overview of the evolving landscape of current knowledge regarding nanosized drug delivery systems, to outline challenges, and to evaluate growth opportunities. The merit of the review stems from the extensive, wide-ranging coverage of the most up-to-date scientific information, allowing unmatched breadth of landscape analysis and in-depth insights.

New strategies for an old problem - Oral vaccines research

New strategies for an old problem - Oral vaccines research Despite their advantages, oral vaccines encounter several challenges. Professor Elizabeth Norton from Tulane University discusses how her team is addressing these issues and their research on developing and testing dmLT and saponin combination adjuvants. The gut is home to a remarkable concentration of the body’s immune cells, particularly antibody-secreting plasma cells. It serves as a critical site for interactions with microbes, exposure to pathogens, and maintaining overall health. Globally, several human vaccines leverage oral delivery routes due to their ability to stimulate mucosal immunity and suitability for mass immunization campaigns. (1) Notable licensed oral vaccines include live-attenuated vaccines for polio, rotavirus, Salmonella typhi, and adenovirus, as well as whole-inactivated vaccines for cholera. These vaccines offer additional benefits, such as eliminating the need for syringes and needles. This is particularly valuable in resource-limited settings, where needle reuse can lead to accidental transmission of bloodborne infections like HIV and hepatitis, and it also mitigates needle-related aversion among individuals.

Topical Application onto the Eyelid Skin: Is it a Feasible Delivery Route of Ophthalmic Drugs?

Topical application of ophthalmic drugs remains to be the preferred delivery method. Eye drops lead the pharmaceutical forms due to ease of application. Despite the poor bioavailability of drugs administered topically, especially related to the dilution and excretion by tear fluid, the absence of controlled drug delivery, and the poor compliance within pediatric and senior populations, eye drops and ointments are still the first choices in eye--related disorders management. Only a few studies have explored the eyelid skin as a site for drug application and transdermal delivery as an alternative route of administration of ophthalmic drugs. Such works have validated the delivery of drugs into the ocular tissues through the eyelid barrier. The eyelid represents a differentiated skin barrier concerning the thickness, the structure of the stratum corneum, the vasculature, and the amount of lipids. This work intends to question why the eyelid, being an accessible, non-invasive, comfortable route of administration is not considered a feasible route for ophthalmic drugs. The eyelid structure is presented, and the anatomical and physiological distinctive characteristics are presented. The work also presents the research work on topical drug application to the eyelid skin that has been published so far.

Pathogen delivery route impacts disease severity in experimental Mycoplasma ovipneumoniae infection of domestic lambs

M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M. ovipneumoniae infection have reported highly variable clinical signs and pathology. Here, we assessed the impact of administering M. ovipneumoniae to the upper respiratory tract (URT) or to the lower respiratory tract (LRT) of two-month-old specific pathogen-free lambs. Lambs were inoculated with PBS (control) or with ceftiofur-treated nasal wash fluid obtained from sheep with natural M. ovipneumoniae infection, monitored for eight weeks, and subsequently euthanized. All lambs in the URT and LRT groups developed a stable infection with M. ovipneumoniae. M. ovipneumoniae infection led to lower weight gains and mild respiratory disease, with significantly greater effects following LRT inoculation compared to URT inoculation. At necropsy, lambs inoculated via the LRT showed consolidation of the cranial lung lobes. In addition, histological signs of alveolar, bronchiolar, and interstitial inflammation were significantly more severe in the LRT compared to the URT group. M. ovipneumoniae loads in the trachea and bronchi also were significantly higher after LRT than URT inoculation. Interestingly, 9/10 inoculated lambs also tested positive for M. haemolytica in nasal swab but not in bronchial swab samples. In summary, our study suggests that bypassing protective mechanisms of the URT by delivering respiratory pathogens to the LRT leads to more severe respiratory disease and lung damage than delivery to the URT.

Antisense oligonucleotide as novel therapies for neurogenetic disorders

Antisense oligonucleotide (ASO) was discovered several decades ago and initially used only as a research tool in the laboratory. In recent years, several ASO therapeutics have been developed for neurological disorders. Some of these therapeutics, including eteplirsen, golodirsen, viltolarsen, nusinersen and inotersen, have been approved by the Food and Drug Administration (FDA) and begun to draw the public's attention as an effective therapeutic approach. These novel therapeutics have shown great performance, while many similar therapeutics are under investigation and in clinical trials. This n-of-1 precision medicine may start a new chapter in the paradigm of therapeutics. Clinicians, clinical geneticists, and genetic counselors may know about this novel therapy, but very few may understand the background in details. During genetic counseling, they have the responsibility to convey the effectiveness, side effects and cost of such therapies to patients and their families. As these target therapies will require precise genetic diagnosis before treatment, healthcare professionals and genetic counselors play a vital role in relating the patients to the corresponding ASO drugs. This review has elaborated the mechanism of ASO therapies, including basic rationales, modifications, side effects and delivery routes. It also systemically summarized the FDA-approved ASO therapeutics and their applications for various neurological disorders, and discussed the limitations and challenges the real-world market may face and issues genetic counselor should take into consideration in the near future.

The Impact of Integrating Open Data in Smart Last-Mile Logistics: The Example of Pamplona Open Data Catalog

Last-mile logistics is one of the most complicated operations in the whole logistic process. This concept describes the final leg of a product travel from a warehouse or hub to specific customers. One of the last-mile logistics challenges that courier delivery companies face is route planning. Ineffective route planning can cause operational delays that cascade and affect several last-mile deliveries. Thus, numerous factors need to be considered to plan and optimize effective delivery routes. These involve many extraordinary and unpredictable events, including weather, traffic conditions, and traffic regulations. A lack of accessible data hinders dynamic, efficient, and reliable route planning, leading to these factors being overlooked. In this paper, we propose the use of open data (OD) to overcome these limitations. OD are information available for anyone to access, reuse, and distribute for free with minimal attribution and sharing restrictions. Therefore, the aim of this work is to examine the impact of incorporating specific open data elements on the performance of the Clarke and Wright algorithm, particularly in calculating savings, and identifying optimal routes. The results we obtained showed the effect of considering OD with an increase rate of approximately 2% on the total distance compared to not considering them.

Optimization of Multi-Vehicle Cold Chain Logistics Distribution Paths Considering Traffic Congestion

Urban road traffic congestion has become a serious issue for cold chain logistics in terms of delivery time, distribution cost, product freshness, and even organization revenue and reputation. This study focuses on the cold chain distribution path by considering road traffic congestion with transportation, real-time vehicle delivery speeds, and multiple-vehicle conditions. Therefore, a vehicle routing optimization model has been established with the objectives of minimizing costs, reducing carbon emissions, and maintaining cargo freshness, and a multi-objective hybrid genetic algorithm has been developed in combination with large neighborhood search (LNSNSGA-III) for leveraging strong local search capabilities, optimizing delivery routes, and enhancing delivery efficiency. Moreover, by reasonably adjusting departure times, product freshness can be effectively enhanced. The vehicle combination strategy performs well across multiple indicators, particularly the three-type vehicle strategy. The results show that costs and carbon emissions are influenced by environmental and refrigeration temperature factors, providing a theoretical basis for cold chain management. This study highlights the harmonious optimization of cold chain coordination, balancing multiple constraints, ensuring efficient logistic system operation, and maintaining equilibrium across all dimensions, all of which reflect the concept of symmetry. In practice, these research findings can be applied to urban traffic management, delivery optimization, and cold chain logistics control to improve delivery efficiency, minimize operational costs, reduce carbon emissions, and enhance corporate competitiveness and customer satisfaction. Future research should focus on integrating complex traffic and real-time data to enhance algorithm adaptability and explore customized delivery strategies, thereby achieving more efficient and environmentally friendly logistics solutions.

The Impact of Using AI in Supply Chain on Corporate Management

As the current market becomes increasingly competitive and labor costs continue to rise, enterprises must explore alternative strategies to enhance their supply chain management for better development and innovation. The main study in this research paper is the potential impact of AI on improving supply chain efficiency. Key components of the supply chain include information processing, inventory management, logistics management and customer feedback. This study focuses on the practical applications of existing AI technologies in supply chain management. The main features are to fasten and animate order data processing, improve order accuracy, simplify and accelerate inventory processes, optimize express delivery routes, and improve customer satisfaction. In addition, AI applications in supply chain management can significantly reduce work time costs and reduce labor costs, enabling companies to develop rapidly and gain a competitive edge in the market.

Dynamic Route Optimization in Last-Mile Delivery Using Predictive Analytics: A Case Study of E-commerce in the U.S.

The last-mile delivery problem is one of the most complex and resource-intensive aspects of modern logistics, especially within the growing e-commerce sector. As online shopping continues to expand, companies are under immense pressure to deliver goods more quickly, efficiently, and at lower costs, all while meeting the demands of increasingly time-sensitive customers. This has created a need for innovative solutions that can tackle challenges related to dynamic traffic patterns, fluctuating customer preferences, and operational constraints such as vehicle capacities and delivery windows. In response to these challenges, this paper explores the application of predictive analytics as a tool for optimizing last-mile delivery routes in real-time.The study begins by identifying the core challenges inherent in last-mile logistics, particularly in the U.S. e-commerce landscape, where the cost of last-mile delivery can represent up to 53% of total shipping costs. With traffic congestion, unpredictable customer availability, and delivery time constraints posing significant hurdles, conventional static route planning models often fall short. In this paper, predictive analytics is proposed as a solution to these challenges, utilizing real-time data to inform more efficient routing decisions. By processing vast amounts of real-time traffic data, customer preferences, and delivery constraints, predictive models can offer a more flexible and responsive approach to last-mile delivery.The research then presents a comprehensive literature review of existing route optimization methods, such as the traditional Vehicle Routing Problem (VRP) and its extensions, including VRP with Time Windows (VRPTW), Dynamic VRP (DVRP), and Capacitated VRP (CVRP). While these models have proven useful, their limitations are exposed when faced with real-time operational complexities in the e-commerce sector. Therefore, this study introduces an advanced dynamic routing model that integrates machine learning algorithms—such as decision trees and neural networks—with traditional VRP frameworks. These machine learning models, trained on historical data, are capable of predicting future traffic patterns, customer behavior, and delivery time windows.A case study is conducted using data from U.S.-based e-commerce companies to demonstrate the practical application of predictive analytics in optimizing last-mile delivery. The case study outlines how predictive models are used to dynamically adjust delivery routes based on real-time conditions, leading to significant improvements in efficiency, cost savings, and customer satisfaction. Key performance indicators such as delivery times, fuel consumption, and vehicle utilization are examined before and after the implementation of the predictive models, with the results showing a reduction in delivery time by 20% and fuel costs by 15%, alongside improved on-time delivery rates.The paper concludes by presenting the proposed dynamic route optimization model as a solution that combines the flexibility and responsiveness of predictive analytics with the robust framework of traditional VRP models. Through the integration of machine learning, real-time data processing, and dynamic routing, the model is shown to significantly improve last-mile delivery efficiency. This study's findings highlight the potential for predictive analytics to revolutionize the logistics industry, particularly in the high-demand e-commerce sector, where quick and reliable delivery is paramount. The research suggests that as e-commerce continues to grow, predictive analytics will play an increasingly critical role in ensuring that last-mile delivery is both cost-effective and responsive to the evolving needs of consumers.

Systemic Clodronate Liposome Treatment for Depletion of Blood-Contacting Phagocytes and Investigation of Their Role in the Control of Bunyavirus Viremia.

During viral infection, phagocytic cells participate in numerous immunological processes. A common approach to elucidate the specific contributions of phagocytic cells is through direct comparison of viral pathogenesis of phagocyte-depleted and phagocyte-intact animals. Clodronate liposomes are a versatile and simple means of depleting phagocytes in any animal model. Selection of clodronate liposome route of delivery can yield systemic or local phagocyte depletion as needed. Here we describe the application of clodronate liposome-mediated depletion of blood-contacting phagocytes to investigate their interactions with La Crosse virus (or other bunyaviruses) in a reductionist model of viremia.

Recent Advancement in Inhaled Nano-drug Delivery for Pulmonary, Nasal, and Nose-to-brain Diseases.

Pulmonary, nasal, and nose-to-brain diseases involve clinical approaches, such as bronchodilators, inhaled steroids, oxygen therapy, antibiotics, antihistamines, nasal steroids, decongestants, intranasal drug delivery, neurostimulation, and surgery to treat patients. However, systemic medicines have serious adverse effects, necessitating the development of inhaled formulations that allow precise drug delivery to the airways with minimum systemic drug exposure. Particle size, surface charge, biocompatibility, drug capacity, and mucoadhesive are unique chemical and physical features that must be considered for pulmonary and nasal delivery routes due to anatomical and permeability considerations. The traditional management of numerous chronic diseases has a variety of drawbacks. As a result, targeted medicine delivery systems that employ nanotechnology enhancer drug efficiency and optimize the overall outcome are created. The pulmonary route is one of the most essential targeted drug delivery systems because it allows the administering of drugs locally and systemically to the lungs, nasal cavity, and brain. Furthermore, the lungs' beneficial characteristics, such as their ability to inhibit first-pass metabolism and their thin epithelial layer, help treat several health complications. The potential to serve as noninvasive self-administration delivery sites of the lung and nasal routes is discussed in this script. New methods for treating respiratory and some systemic diseases with inhalation have been explored and highlight particular attention to using specialized nanocarriers for delivering various drugs via the nasal and pulmonary pathways. The design and development of inhaled nanomedicine for pulmonary, nasal, and respiratory medicine applications is a potential approach for clinical translation.

Decarbonizing the Transport of Microalgae-based Products -The Role of E-mobility.

The decarbonization of road transport is a precondition for achieving carbon neutrality. Battery-electric vehicle technology, driven by several patents, can make this a reality. In this bias, the objective of the article is to shed light on the ongoing debate about the potentially important role of the adoption of electric vehicles in the transport of microalgae-based products to help them advance to a cleaner life cycle. Five routes, including unimodal and multimodal conditions, were defined to assess the carbon emissions of the transport system and, more specifically, of road transport. The headquarters of market-leading microalgae manufacturers were selected as the origin of the routes and, as the destination, regions that sustain them. The results reveal the supremacy of road transport of microalgae-based products using electric vehicles powered by nuclear, hydroelectric, and wind, followed by biomass and photovoltaic energy. They also show that the positive impact of wind, water, and photovoltaic energy on the climate, added to the lower battery charging costs and the greater opportunity to generate revenue from the sale of carbon credits, make their trade-offs. The exquisite results of this study convey key messages to decision-makers and stakeholders about the role of electromobility in building a zero-carbon delivery route.

Meal Delivery Routing Problem with a Hybrid Fleet of Riders and Autonomous Vehicles under Dynamic Environment

Meal Delivery Routing Problem with a Hybrid Fleet of Riders and Autonomous Vehicles under Dynamic Environment

Proteomics analysis revealed the therapeutic role of adipose-derived mesenchymal stem cells on radiation-induced colorectal fibrosis in rats.

Radiation-induced colorectal fibrosis (RICF) is a chronic condition that can develop after pelvic radiation therapy for colorectal cancer. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as promising candidate for fibrosis treatment, yet the mode of action of ADSC upon RICF remains obscure. This study aimed to investigate the optimal delivery route, treatment timing, anti-fibrotic effects, and underlying mechanisms of ADSCs upon RICF. The RICF rat model was constructed by single dose of 20 Gy irradiation, and ADSCs were delivered via diverse ways (e.g., tail vein injection, abdominal aorta injection, peritoneal injection, or perianal tissue injection) at different frequencies (once, twice, or thrice a week) for 10 weeks. TMT-labelled proteomic and phosphoproteomic analysis was conducted for dissecting the underlying mechanisms of ADSCs upon RICF. ADSCs were co-cultured with primary human intestinal fibroblasts to verify the anti-fibrotic effects upon radiation-induced fibroblasts. Additionally, 4D label-free proteomic analysis and 4D-parallel reaction monitoring were carried out to explore their molecular mechanisms. RICF rats revealed better outcomes after intraperitoneal injection of ADSCs rather than the relative ways, and in particular, those with thrice-weekly injections showed effective prevention and improvement in RICF. Proteomic and phosphoproteomic analyses, together with multifaceted analyses (e.g., co-culture, 4D-PRM analysis), indicated Cytochrome b-245 alpha chain (Cyba) as a candidate target in mediating the efficacy of ADSCs upon RICF. This comprehensive multilevel proteomic study provides valuable insights into the molecular mechanisms underlying RICF and enhances understanding of the potential of ADSCs-based cytotherapy.

A narrative review on potential applications of spanlastics for nose-to-brain delivery of therapeutically active agents.

Spanlastics, which are commonly referred to as elastic niosomes, presents a modified advancement in the area of colloidal system based drug delivery carriers. They are different from niosomes, which are non-ionic surfactant vesicles in having an edge activator. Initially, they were described as ocular drug delivery systems in 2011 by Kakkar and Kaur. Spanlastics have discovered a wide range of applications via different routes of administration. The purpose of this article is to provide information about spanlastics, a newly developed drug delivery system for the management of diseases pertaining to the Central Nervous System (CNS) via intranasal route. The article begins with the details on spanlastics and their composition, their benefits over traditional niosomes, and the mechanism underlying their enhanced absorption. Their applications through various routes of administration in a variety of diseases for a variety of drugs have been discussed. Furthermore, the article explains the nose to brain delivery channels and the advantages that this route offers over conventional delivery routes. Finally, the article discusses the studies encompassing the drug candidates that have been formulated as intranasal spanlastics for the management of different diseased conditions along with the future prospects of this emerging drug delivery system.

Optimizing Drone-Based Delivery Using the Pity Beetle Algorithm A Novel Approach.

The Travelling Salesman Problem with Drones (TSP-D) has emerged as a significant optimization challenge in last-mile delivery systems. Addressing scalability issues with datasets exceeding 250 nodes, this study introduces the Pity Beetle Algorithm (PBA), a novel metaheuristic. The PBA demonstrates superior performance in balancing exploration and exploitation to optimize delivery routes effectively. Results from new simulations conducted for this journal show delivery time reductions in a broader range of scenarios, with improvements up to 60% over standard benchmarks. Statistical analyses confirm the algorithm’s capability to enhance computational efficiency and scalability. Additionally, the PBA’s dynamic tuning mechanisms enable it to adapt effectively to varying dataset sizes and configurations. Beyond its computational benefits, this study underscores the real-world applicability of the PBA in logistics, providing industries with a robust tool to optimize delivery times and reduce operational costs. This research opens avenues for integrating PBA with hybrid models and real-time optimization techniques, further enhancing its potential to tackle complex logistical challenges.

Risk Factors Associated with Pediatric Asthma Hospitalization: A Retrospective Case-Control Study

Objective: To evaluate the risk factors associated with asthma in children hospitalized at Hospital Belen de Trujillo. Materials and methods: An analytical study of retrospective cases and controls was carried out in which 258 clinical histories of children between 5 to 14 years of age who were hospitalized in the Hospital Belen de Trujillo (HBT) during the period 2015-2019 were included, which were grouped into 129 histories of children who had been hospitalized for asthma (cases) and 129 histories of children hospitalized for a different cause (controls). The frequency distribution will be calculated, the Chi-square statistical test will be used, the odds ratio will be obtained and the 95% confidence interval will be calculated; finally, a multivariate analysis will be performed by means of logistic regression to determine whether the influence of other variables generates a greater risk of developing asthma in children. Results: The multivariate analysis showed that the factors: cesarean delivery, non-exclusive breastfeeding, history of bronchiolitis, obesity and maternal age together predict 92. 0% of the cases of asthma; however, taking the influence of all the factors at the same time, it was found that the cesarean delivery route, non-exclusive breastfeeding, obesity and maternal age are significant for the regression (p<0.05), while the factor history of bronchiolitis is not significant (p>0.05). Likewise, when the bivariate analysis of the five variables studied was performed and the Chi-square test was applied, it was found that all five factors were significant (p<0.05) for asthma in children at Hospital Belen de Trujillo. Conclusion: The factors cesarean delivery route, non-exclusive breastfeeding, history of bronchiolitis, obesity and maternal age are associated with asthma in children hospitalized at HBT.

Is Quick Delivery Related to Quick-Commerce Environmentally Sustainable?

The rapid expansion of quick-commerce (q-commerce) businesses, which promise quick last-mile delivery, requires an urgent assessment of their environmental sustainability. This study investigates the sustainability of the q-commerce business model, which relies heavily on electric vehicles (EVs) and dark stores for last-mile delivery services, and assesses the environmental impact of express-delivery operations, particularly in terms of greenhouse gas (GHG) emissions. It examines the ability of EVs and dark stores under Q-Commerce to reduce the carbon footprint compared to traditional online last-mile delivery methods and evaluates the environmental pollution potential of increased delivery frequency and faster last-mile delivery in terms of GHG emissions. By analysing data from various q-commerce companies and last-mile deliveries, the paper provides insight into the trade-off between the benefits of fast delivery and its environmental sustainability. The results highlight the complexities of achieving sustainability in the rapid last-mile delivery sector by combustion vehicles and propose a framework for integrating environmentally friendly practices to reduce overall environmental impacts, such as optimizing electric vehicle adoption and delivery routes. The conclusion of the paper discusses the feasibility and significance of establishing a more sustainable q-commerce environment, as well as its limits and future prospects.

Differential Regulatory Effects of Probiotics on Bone Metabolism by the Status of Bone Health and Delivery Route.

Probiotics are known to have favorable effects on human health. Nevertheless, probiotics are not always beneficial and can cause unintended adverse effects such as bacteremia and/or inflammation in immunocompromised patients. In the present study, we investigated the effects of probiotics on the regulation of bone metabolism under different health conditions and delivery routes. Intragastric administration of Lactiplantibacillus plantarum to ovariectomized mouse models for mimicking post-menopausal osteoporosis in humans substantially ameliorated osteoporosis by increasing bone and mineral density. In contrast, such effects did not occur in normal healthy mice under the same condition. Interestingly, however, intraperitoneal administration of L. plantarum induced bone destruction by increasing osteoclast differentiation and decreasing osteoblast differentiation. Furthermore, when L. plantarum was implanted into mouse calvarial bone, it potently augmented bone resorption. Concordantly, L. plantarum upregulated osteoclastogenesis and downregulated osteoblastogenesis in in vitro experiments. These results suggest that L. plantarum can have distinct roles in the regulation of bone metabolism depending on bone health and thedelivery route.