Abstract

Bacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers. Moreover, attributing to considerable intrinsic immunogenicity, BEVs are able to interact with the host immune system to boost immunotherapy as the novel nanovaccine against a wide range of diseases. Towards these significant directions, in this review, we elucidate the nature of BEVs and their role in activating host immune response for a better understanding of BEV-based nanopharmaceuticals’ development. Additionally, we also systematically summarize recent advances in BEVs for achieving the target delivery of genetic material, therapeutic agents, and functional materials. Furthermore, vaccination strategies using BEVs are carefully covered, illustrating their flexible therapeutic potential in combating bacterial infections, viral infections, and cancer. Finally, the current hurdles and further outlook of these BEV-based nanopharmaceuticals will also be provided.

Introduction

Vesiculation is a crucial and fundamental process across all kinds of species to produce the extracellular vesicles that serve as essential mediators of basic physiological events [1]. These nanovesicles are filled with molecular patterns originated from parent cells, including metabolites, nucleic acids, proteins, and signaling molecules, to maintain cell growth and homeostasis [2, 3]. Biological regulation by extracellular vesicles is widespread across both prokaryotes and eukaryotes [4]. Notably, bacteria, as one of the major inhabitants in the human body, establish intricate relationships with host health and disease, wherein bacterial extracellular vesicles (BEVs) are indispensably involved in these processes [5, 6]. With the increasing and deep understanding of their biological function, BEVs are found to influence various cellular behaviors, including the transport of genetic information, phage infection, mediation of metabolism, as well as interaction between bacteria-bacteria and bacteria-host [7, 8].

Particularly, BEVs are characterized as nanosized nanoparticles, surrounded by lipid-bilayer membranes, ranging from 20 to 400 nm in diameter [7]. In account of the diversity of bacterial types and biogenesis mechanisms, the BEVs could carry versatile cargos inherited from mother cells, such as lipopolysaccharides (LPS), endotoxins, genetic information, cytosolic and membrane proteins [9]. By thanking the unique structure and intrinsic properties of BEVs, these naturally occurring nanovesicles attract the research interest to be developed as novel nanopharmaceuticals, prompting further exploration of their biomedical applications [10, 11]. Generally, BEVs are widely evaluated as biotherapeutics in different forms. Firstly, these nanovesicles with hollow structures could serve as novel drug delivery platforms, facilitating the transport of diverse bioactive molecules and therapeutic cargo to the recipient cells at the lesion site [12]. Thanks to the stability of naturally-occurring membrane structure, the BEVs-based drug delivery platform could carry the therapeutic genetic tools (e.g. siRNA, CRISPR-Cas9, etc.), protecting them from enzymatic degradation or hydrolysis in the complex physiological environment [13, 14]. Besides, benefiting from the ease of modification, BEVs-based drug delivery platforms could efficiently load the small molecular therapeutics [14], or directly produce the synthetic cargo (e.g. antigens, enzymes, therapeutic proteins, etc.) on the BEVs by editing the desired gene in parent bacteria. The BEVs-based drug carriers are also featured in their capability for targeting delivery toward the disease area to enhance drug accumulation and availability [15]. Moreover, the BEVs drug delivery platform can integrate with functional materials, to facilitate combinational therapy (e.g. photodynamic therapy, photothermal therapy, etc.) and maximize the synergistic therapeutic efficiency [16].

Conclusion and further perspective

In this review, we comprehensively summarize the development of BEV-based nanopharmaceuticals to facilitate disparate biomedical applications in recent years. Amongst the unique advantages and functions of BEVs, we demonstrated the tremendous potential of applying these naturally occurring nanovesicles to establish a myriad of innovative therapeutic strategies for new-generation pharmaceuticals evolution, especially in the versatile bioactive cargo delivery and powerful vaccination approaches.

Taking the unique merits of nanovesicles, the structural stability, ease of cargo loading, promising penetration across physiological barriers, and specific targeting capabilities endow the BEVs application to be beneficial in delivery for a wide range of therapeutics. Particularly, the naturally occurring membrane structure of BEVs enables targeting delivery of therapeutic genetic tools (e.g., siRNA, DNA, CRISPR-Cas9, etc.) in the physiological, preserving stability and bioactivity, thus enhancing gene therapy. Leveraging the ease of genetic modification in parent bacteria, protein cargo, such as enzymes and antigens, can also be directly expressed within BEVs, optimizing loading efficiency compared to conventional delivery platforms. Furthermore, advancements in nanotechnology and material science have witnessed the integration of functional materials with BEV delivery platforms to achieve combinational therapy, thereby further improving the synergistic therapeutic efficacy.

Abstract

     5-10% of all breast cancers are associated with mutations in hereditary breast cancer genes several of which are involved in the DNA damage response.

     BRCA1 and BRCA2 mutation is not associated with poor prognosis in breast cancers, but infact better prognosis when treated with chemotherapy in comparison to similar non BRCA mutated breast cancers.

    Treatment with the small molecule PARP inhibitor olaparib after chemotherapy improves overall survival in patients with early breast cancer and germline BRCA1 or BRCA2 mutations.

     Platinum based chemotherapy is highly active in those with germline BRCA1 or BRCA2 mutations but cross resistance between platinum agents and PARP inhibitors can be mediated by somatic “reversion mutations” in BRCA1 or BRCA2 and is a clinical challenge.

     Understanding the underlying mechanisms of overlapping or distinctive resistance is vital to therapy development in this evolving area of translational medicine.

Introduction

     Approximately 5% to 10% of the 2.3 million breast cancer cases diagnosed annually are associated with a mutation in a known hereditary breast cancer predisposition gene such as BRCA1 or BRCA2.1,2 The integration of genomics into the standard diagnostic pathways for breast cancer patients and the availability of targeted treatment approaches for those with hereditary breast cancer predisposition gene mutations means that the management of these patients is now distinct to that a decade ago. In this review, we discuss the recent advances made in systemic treatments for hereditary breast cancer and highlight future challenges that must be addressed for improvements in clinical outcomes to be achieved in this distinct subgroup.

Hereditary Breast Cancer Genes

     Many of the germline mutations associated with hereditary breast cancer occur in “caretaker” tumor suppressor genes (genes whose normal function is to maintain the integrity of the genome and whose dysfunction leads to genome instability) and include BRCA1, BRCA2, PALB2, ATM, CHEK2, and p53.3 For example, germline deleterious mutations in BRCA1 (gBRCA1m) or BRCA2 (gBRCA2m), which play key roles in DNA repair by homologous recombination (HR), are associated with an increased lifetime risk of developing breast, ovarian, prostate and pancreatic cancer.2,4,5 gBRCA1m carriers have a cumulative lifetime breast cancer risk of 46% to 60% and when diagnosed with breast cancer typically have the basal-like, triple negative (B-L, TNBC), subtype of the disease. gBRCA2m carriers have a cumulative lifetime breast cancer risk of 43% to 55% and tend to develop estrogen receptor-positive (ER+), luminal B subtype, breast cancers (significantly more so than for gBRCA1m carriers).6, 7, 8, 9 gBRCA1/2m breast cancers in those who have a strong family history are usually detected at a younger age than sporadic breast cancers.

Disclosure

     E.H.-J. is a clinical PhD fellow funded by Cancer Research UK and AstraZeneca. A.T. is a consultant for AstraZeneca, Merck KGaA, Artios, Pfizer, Vertex, GE Healthcare, Inbiomotion, MD Anderson Cancer Centre; has received grant/research support from AstraZeneca, Myriad, Medivation, and Merck KGaA; and is a stockholder in Inbiomotion. Stands to gain from the use of PARP inhibitors as part of the ICR’s “rewards to inventors” scheme. C.J.L. makes the following disclosures: receives and/or has received research funding from: AstraZeneca, Merck KGaA, Artios. Received consultancy, SAB membership or honoraria payments from: Syncona, Sun Pharma, Gerson Lehrman Group, Merck KGaA, Vertex, AstraZeneca, Tango, 3rd Rock, Ono Pharma, Artios, Abingworth, Tesselate, Dark Blue Therapeutics. Has stock in: Tango, Ovibio, Enedra Tx., Hysplex, Tesselate. C.J.L. is also a named inventor on patents describing the use of DNA repair inhibitors and stands to gain from their development and use as part of the ICR “Rewards to Inventors” scheme.

Abstract

The application of Artificial Intelligence (AI) is rapidly transforming various industries, and the pharmaceutical industry is no exception. AI is increasingly being used to automate, optimize and personalize various aspects of the pharmacy industry, from drug discovery to drug dispensing. In this context, this paper explores the potential of AI to revolutionize the pharmacy industry, by discussing the current and future applications of AI in the industry. We will examine how AI is being used in drug discovery, personalized medicine, drug safety and quality control, inventory management, and patient counselling. We will also discuss the challenges and limitations of AI in the pharmacy industry, such as data privacy, ethical concerns and regulatory barriers. The paper will argue that AI has the potential to revolutionize the pharmacy industry by enabling faster drug discovery, improving patient outcomes, reducing costs, and increasing the efficiency and accuracy of various pharmacy operations. The old pharmacy system relied on manual processes and human decision-making, while the new AI pharmacy system automates routine tasks, provides personalized treatment plans, and reduces costs while improving patient outcomes. However, it is important to ensure that AI is used ethically and responsibly, and that its impact on the workforce and society is carefully considered. The major benefit of integrating AI into specific applications within the pharmacy field is improved accuracy and efficiency in patient care. Overall, this paper will provide an insight into the future of the pharmacy industry, and the transformative potential of AI in this field.

Introduction

The conventional pharmacy system relies heavily on manual processes and human expertise, which can lead to inefficiencies, errors, and delays. For example, the process of filling a prescription involves several manual steps, such as interpreting the prescription, dispensing the medication, and verifying the dosage and frequency1, 2, 3. These manual processes are prone to errors and can be time-consuming. Moreover, the conventional pharmacy system lacks the ability to personalize medication regimens for individual patients, which can limit the efficacy of drug therapy. However, by using AI-powered tools like AI, pharmacies can enhance their operations and overcome these limitations. AI can help automate various aspects of the pharmacy workflow, from prescription interpretation to drug dispensing, reducing the risk of errors and improving efficiency. Additionally, by analyzing large amounts of patient data, AI can assist pharmacists in developing personalized medication regimens that are tailored to the patient’s unique needs and medical history. While the conventional pharmacy system has been effective in providing patients with necessary medications, it is limited by its manual processes and lack of personalization. The use of AI-powered tools like AI can overcome these limitations, making the pharmacy system more efficient, accurate, and personalized, ultimately leading to better patient outcomes4, 5, 6, 7.

Conclusion, scope for future work and limitations

In conclusion, the potential applications of AI in pharmacy can revolutionize the industry, providing numerous benefits for both pharmacists and patients. From medication management to drug discovery and chronic disease management, AI technology can improve the accuracy and safety of medication dispensing, accelerate the drug development process, and help to improve patient outcomes. The implementation of AI technology can also help to reduce healthcare costs by improving efficiency and reducing errors. However, it is important to note that the implementation of AI in pharmacy also presents some limitations and challenges that need to be addressed. For example, there may be concerns around patient privacy and security when using AI-powered systems to monitor patient data. Additionally, there may be a need for pharmacists to undergo additional training to effectively use and integrate AI technology into their practice. Nonetheless, with proper implementation and management, the benefits of AI in pharmacy far outweigh the potential limitations and challenges, paving the way for a brighter future in healthcare.

While the potential applications of AI in pharmacy are vast, there is still much work that needs to be done in terms of research and development. One potential area for future study could be the integration of AI technology with other healthcare systems, such as electronic health records (EHRs) or telemedicine platforms. This could allow for a more comprehensive and coordinated approach to healthcare delivery, improving patient outcomes and reducing healthcare costs. Another area for future research could be the ethical considerations around the use of AI technology in pharmacy. As the technology continues to evolve, it is important to consider issues such as data privacy and security, algorithmic bias, and the potential for AI systems to replace human jobs. Addressing these issues in a thoughtful and proactive manner can help to ensure that the implementation of AI in pharmacy is both effective and ethical. By continuing to explore these areas of study, we can further unlock the potential of AI technology in pharmacy and pave the way for a more efficient and effective healthcare system.

Abstract

Introduction

Materials and methods

DPPH

Microbial studies

Result and discussion

Microbial studies

Conclusion

Acknowledgements

References

Abstract

     Nanotechnology involving biopolymers is comprehensively used in biomedical applications, planning sciences, and food development. The present work describes the synthesis, characterization, and application of carrageenan and zinc oxide nanoparticles (ZnONPs) based hydrogel. The synthesized hydrogels were subsequently characterized using FTIR, XRD, SEM, and TG-DTA. The swelling property, antioxidant activity, and whole blood clotting effectiveness of the Carrageenan hydrogel, and Carrageenan Hydrogels Impregnated with Zinc Oxide Nanoparticles were evaluated. The Carrageenan + ZnONPs (C/ZnONPs) hydrogels showed good antioxidant, and blood clotting activity than the pure carrageenan hydrogel. In addition, the stable C/ZnONPs hydrogels exhibit good antimicrobial activities against both Gram-negative and Gram-positive bacterial strains. Biofilm analysis showed that C/ZnONPs hydrogels have excellent anti-biofilm potential in both inhibition and disruption of preformed biofilm. The obtained results suggested that the carrageenan and Zinc oxide nanoparticles based hydrogel have promising biological applications.

Introduction

     Pathogenic microorganism resistance to frequently used antibiotic substances have become an important health concern in the 21st century. The development of microorganism resistance to antibiotics has significantly increased morbidity and mortality, longer hospitalization and increased health care costs.[1] Resistance is increasing against antibiotics, particularly to the first line, inexpensive, and broad-spectrum antibiotics, but also to the newly developed antibiotics; since the development of novel alternative is necessary.[2,3]

In the specific case of wound management there are several reports of the microorganism resistance to the drug used to manage wounds.[4] The role of microbial infections in the development of wound infections is well established, the life threatening nature of the wound infections has maximized its importance in human health. In addition, the cost of medication for wound management is also high.[5,6] Hence the exploration of new substance for the wound management is very important.

Conclusion

     The synthesized C/ZnONPs hydrogels was produced by a simple and efficient method, performing proper swelling capacity and much better mechanical properties. It exhibited better antioxidant, blood clotting activity and also possess excellent antibacterial and biofilm efficacy against B. subtilis, S. aureus, E. coli and K. pneumonia. The present study confirmed that C/ZnONPs hydrogel have multi-potential property. Thus, the present study suggests that this bio-reduction practice is a well suitable system for large-scale production. The blood clotting and biofilm efficacy were tested in this study only at the grassroot stage which needs to be addressed further.

Abstract

Introduction

Polyacrylamide hydrogels and their polymerization

Polyacrylamide hydrogel in cell biology and drug delivery system

Classification of hydrogels: a broad overview

Homo-polymeric hydrogels

Co-polymer hydrogels

Semi-interpenetrating network

Interpenetrating network

Recent progress (2019–2022) of polyacrylamide-based hydrogel composites

Swelling and degradation behaviour of PAM hydrogels

Mechanical properties of PAM hydrogel composites

Tribological and rheological properties of PAM composites

Magnetic hydrogel composites

Biological properties of the PAM hydrogel composites

Applications of polyacrylamide hydrogels

Conclusions

Scope for the future work

Acknowledgements

References

Abstract

     Polyacrylamide hydrogels have made an immensely important place in various fields having bio-compatibility, high water-holding capacity, tunability and cheap synthesis, which has attracted researchers’ attention. Polyacrylamide can be chemically infused with other elements or compounds to find applications in magnetic biosensors, drug delivery, cartilage repair and wound dressing. This paper throws light on the brief introduction of hydrogels and their classification. The polymerization method of polyacrylamide hydrogel followed by its clinical uses (cell biology and drug delivery) is adorned in the report. Keeping at the centre, the recent highlights on the research work done on polyacrylamide hydrogel composites using various reinforcing additives are crucially explored first time in the present report. The improvement practice in the strength, bonding and self-healing of the polyacrylamide hydrogel is demonstrated by the encapsulation of nanoparticles like silicon, carbon nanotubes, gelatine, cellulose, etc. The clinical aspects of the polyacrylamide are corroborated by the cell viability, proliferation and migration. Thus, polyacrylamide hydrogels are emerging candidates, precisely illuminated in the review, which can be an influential highlight designed for upcoming research.

Introduction

     Hydrogels are flexible polymers with excellent biocompatibility. Due to their three-dimensional network, hydrogels have high water-holding capacity. Further, hydrogels have the ability to form blends by using more than one monomers and cross-linkers. Chemical infusion of hydrogels has also been tested with several biocompatible materials. These hydrogel composites are tested for a ‘new generational’ changes in existing applications. This infusion using corresponding salts followed by reduction using a suitable reducing agent forms nanoparticles suspended in the hydrogel. Research in magnetic bio-sensing materials has tested hydrogels infused with magnetic nanoparticles also called ferrogels. For applications like cartilage replacement as well, hydrogel-based composites are carefully prepared for specific cartilage-like properties [1, 2]. Gels are formed when crosslinker forms bonds laterally linking two polymeric chains. This is much like the two sugar phosphate DNA backbones that are joined by chromosome pairs. Except that, the polymeric chains are flexible, unlike DNA backbones! Without cross-linking, the polymeric chains will dissolve into the aqueous phase and only interaction between the chains is through a physical bond. Cross-linking also decides the strength-related properties of the gel. Optimizing the cross-linking method and the cross-linking ratio is essential for strength-related properties.

Conclusions

     Polyacrylamide hydrogels are emerging polymers due to their unique properties, which have made them useful in fields like cartilage repair, wound dressing, contact lenses, drug delivery and biosensors. The PAM hydrogel can be prepared by a monomer unit along with a cross-linker mixed in a suitable quantity. The PAM composites were fabricated by introducing some nanoparticles and reducing them to change these cations/anions into metal ions. The present review described the introduction of hydrogels with their different types, based on the polymeric network structure. The PAM hydrogels along with different nanoparticles like TiO2 and CNTs are turned with high strength ([ 0.43 and 2.340 MPa compressive strength and elastic modulus, respectively) composites. However, the puncture resistant of the PAM was also enhanced with these nanoparticles, estimated using the needle insertion technique. The tribological and magnetic investigations (magnetic saturation 1.41 emu/g) revealed an improved performance of PAM with encapsulation of nanoparticles due to the fine-grained structure and lubrication effects (created by CNTs). Furthermore, the biological activity of PAM composites was remarkably important and ideal for the implementation in biomedical research. Thus, in short, this review report is an important highlight for PAM hydrogel composites and can provide a prominent direction to future research based on the PAM hydrogels for biomedical applications.

Abstract

Introduction

Materials and methods

Characterizations

Results and discussion

Optimized reaction conditions

FTIR spectra analysis

SEM–EDS analysis

XRD analysis

TGA analysis

Conclusion

Declarations

References

Abstract

     An interpenetrating polymer network (IPN) containing gum acacia (GA), poly(methacrylic acid) (MAA), and poly(acrylic acid) (AA) was developed using a two-step aqueous polymerization method. Firstly, semi-IPNs were produced by radical polymerization of MAA chains onto GA in the presence of ammonium persulfate as a free radical initiator and N, N′-methylene-bisacrylamide (MBA) as a cross-linking agent using a microwave heating. To obtain a semi-IPN with a higher swelling percentage, several reaction parameters such as initiator, monomer, and crosslinker concentrations were varied. The percentage swelling (%S) was highly dependent upon the reaction conditions. The optimal reaction conditions for maximal %S were 2.55 × 10–2 mol/L initiator concentration, 12 mL solvent, 0.424 × 10–3 mol/L of monomer, and 2.16 × 10–2 mol/L cross-linker concentration, according to the findings. GA-g-poly(MAA) was the name to given to the semi-IPN. Second, IPN was created by grafting AA chains onto a GA-g-poly(MAA) matrix that had been optimized. The IPN was named as a GA-g-poly(MAA-IPN-AA). The reduction of silver ions to silver nanoparticles (AgNPs) was carried out by heating the mixture of flower extract of Koelreuteria apiculate under microwave radiation.

Introduction

     Hydrogels are three-dimensional (3D) networks formed by the crosslinking of hydrophilic polymers [1, 2]. They might swell while maintaining their network structure by absorbing signifcant amounts of water or biological fluids. The inclusion of hydrophilic groups such as -OH, -CONH, -CONH2, -COOH, and -SO3H along the polymer chain contributes to their ability to absorb a large amount of water [1]. Polysaccharide hydrogel networks have received a lot of attention in recent years [3–5]. The physico-chemical properties of these hydrogels frequently differ significantly from those of the macromolecular constituents. Hydrogel characteristics can also be altered utilizing a range of physical and chemical crosslinking techniques [3, 6]. Various researchers have examined a number of polymeric systems to create hydrogels [7]. The polymer composition can be classified as natural polymeric hydrogels, synthetic polymer hydrogels, and or a combination of both [7]. Because of their non-toxicity, low cost, permeability, and biocompatibility, hydrogels have gotten a lot of attention in a variety of sectors [8–10].

Conclusion

     Antimicrobial materials have been studied extensively in response to rising microbial resistance to traditional antibiotics and disinfectants. Natural polysaccharidebased hydrogels and their composites containing metal nanoparticles could be suitable for antibacterial applications in some cases. Using a microwave irradiation approach, we were able to successfully synthesis GA-gpoly(MAA) and GA-g-poly(MAA-IPN-AA) based hydrogels from GA. APS and MBA being used as initiator and cross-linker, respectively. To achieve maximum %S of semi-IPN (588%) and IPN (500%), diferent parameters were optimized. The formation of cross-linked hydrogels and hydrogel composites with AgNPs was successfully demonstrated using FTIR analysis. The SEM investigation of hydrogel networks reveals a variety of morphologies, which could be attributed to structural diferences between semi-IPN, IPN, and their composites with AgNPs. SemiIPN, IPN and their composite showed superb antibacterial potential against E. coli, M. luteus, P. aeruginosa, Rihzobium species, and S. aureus, and may be used to treat a variety of infected efuents. Such interconnected hydrogels will give superior material properties, particularly in biomedical research, to prevent biomaterialassociated infections as well as general pathogenic invasions into the body. The synthesized hydrogel samples will lead to enhanced applications in the future, as well as a deeper knowledge of material interactions. The eforts to improve the property profle of cross-linked hydrogels are still on, with the hope of improving overall performance in terms of water uptake capacity, biocompatibility, and biodegradability.

Abstract

Keywords

Introduction

Methods

Results

Discussion

Conclusion

Author contributions

Availability of data

Conflicts of interest

Acknowledgements

References

Article Info

Figures

Tables

Related Articles

Abstract

Introduction It has been suggested that the future of diagnostic imaging relies on engagement in research and evidence-based practice. This implies a role transition from a clinical radiographer to a clinical radiographer-researcher. Clinical radiographers’ stimuli for engaging in research in Nordic countries are unknown. This study aimed to address this gap.

Methods
Cross-sectional data collection via an online questionnaire on facilitators for and barriers to participation in radiography research was carried out among 507 clinical radiographers in public healthcare in the Nordic countries: Denmark, Finland, Norway and Sweden.

Results
Support from colleagues (odds ratio [OR] 2.62) and other professionals (OR 2.74), and self-esteem in research skills (OR ≥ 2.21), were facilitators for radiography research. Lack of knowledge and skills to conduct research (OR 2.48) was revealed to hinder radiographers’ participation in research. The absence of a radiography research culture in the workplace explained non-participation in research (OR 1.75).

Introduction 

It has been suggested that the future of diagnostic imaging relies on engagement in research and evidence-based practice (EBP).1e4 While radiologists and physicists have a long tradition of conducting research in medicine and radiation physics, radiographers are still in the initial stages of radiography research, but academic development of radiographers is ongoing while they usually perform research studies alongside university teaching.5e7 Radiography research has been found to address, for example, radiographic technology and patient well-being and care.8,9 There are several reasons to investigate clinical radiographers’ stimuli for engaging in radiography research. One is radiographers’ responsibility for and expertise in patient care in diagnostic imaging.

Abstract

1. Introduction

2. Experimental section

3. Result

4. Discussion

5. Conclusion

Declaration of competing interest

Acknowledgements

References

Abstract

     Hydrogel is a nature scaffold that can degraded in animal body and can be used as a drug delivery system, we hypothesized that patch made of three layers of hydrogel with different PLGA nanoparticle drugs (bio-patch) can be used to decrease venous neointimal hyperplasia. Rat inferior vena cava (IVC) patch venoplasty model was used. Samples from rat IVC direct suture (DS), decellularized thoracic artery patch (TA) venoplasty and bovine pericardial patch (BPP) venoplasty were examined at day 14 after implantation. Sodium alginate and hyaluronic acid (SA/HA) hydrogel was used, three layers hydrogel patch (control) and three layers hydrogel patch with PLGA nanoparticle drugs (bio-patch) were used in rat IVC venoplasty. Patches were harvested at day 14 and analyzed. In rats, TA and BPP patch showed a thicker neointima and adventitia compared to the DS, there were larger numbers of CD68 and PCNA positive cells in both groups. The control hydrogel patch showed much thinner neointima and adventitia compared to TA and BPP patches. In both of the neointima and peri-patch area, bio-patch showed significantly fewer smooth muscle cells, fewer CD68, fewer PCNA positive cells, fewer collagen-1 positive cells, fewer p-smad2 positive cells, fewer TNF-α positive cells compared to control hydrogel patch. Bio-patch made of hydrogel and PLGA nanoparticle drugs showed a thinner neointimal thickness, and is biocompatible to the animal body.

Introduction

     Prosthetic vascular grafts like Dacron and expanded poly tetra fluoroethylene (ePTFE) have a lower patency rate in peripheral bypass surgeries [1,2]. Both grafts showed poor long-term patency rate when the diameter is smaller than 6 ​mm [3]. In addition, biological graft like cryopreserved allografts, bovine or porcine pericardium, are also commonly developed as vascular grafts [[4], [5], [6]]. However, these materials have a risk of infection, foreign body reaction as non-autologous materials, meanwhile they cannot be absorbed by the body, which limit their application [7]. Along with the advancement of material science and technologies, various of novel materials are emerging and under investigation in vascular surgery [[8], [9], [10]]. Decellularized fish swim bladder also showed potential application as tube and patch grafts [3], plant leaf can also be used a patch to repair rat inferior vena cava (IVC) [11,12]. Great progress has been made in the field of vascular patches recently, however, the big challenge of neointima formation still not be solved [13,14].

Conclusion

     In conclusion, we showed a novel idea to fabricate a three layers vascular patch with different PLGA nanoparticle drugs (bio-patch), this bio-patch can effectively decrease neointimal hyperplasia in a rat IVC venoplasty model; this research showed that the bio-patch may be a potential substitute of other prosthetic patches in vascular surgery.

Abstract

     This study integrated multiple objective decision-making approaches including data envelopment analysis (DEA), rough set theory and TOPSIS method for exploring the competitiveness of pharmaceutical multinational enterprises. Firstly, this study applied an advanced two-stage network DEA to measure the R&D efficiency and business performance of pharmaceutical multinational enterprises (PMNEs) listed in the Forbes Global 2000 and ranked these PMNEs by using rough set theory, DEA and TOPSIS method. In addition, differences in environmental, social, and governance (ESG) performance across three continents were investigated. Findings show that North America is significantly the best (worst) region in terms of business performance (R&D efficiency) while Europe is significantly the best (worst) region in terms of R&D efficiency (business performance). Alfresa Holdings Corporation, a PMNE from Japan, is the only PMNE that is efficient from both an R&D and business performance perspective. European PMNEs have significantly better environmental and social performance than other regions, however, they have the worst governance performance. Overall, this study provides insights to managers and investors into the application of various methods for accurately measuring performance and ranking multinational enterprises.

Introduction

     The pharmaceutical industry is one of the most important and competitive industries in the world, it not only has a critical role in the health maintenance of individuals but also in economic growth (Sharma & Modgil, 2019). Pharmaceutical firms have spent a substantial proportion of their time and investment in research and development (R&D) (Rao, 2020). In 2018, R&D expenditure in the pharmaceutical industry was 179 billion U.S. dollars globally (Mikulic, 2020). A correct grasp of the R&D efficiency of the industry is required to improve resource allocation and thereby prevent either excess or shortage of resource inputs (Liu & Lyu, 2020). According to Lu et al. (2019), evaluating multiple indicators simultaneously is useful for appropriate decision-making. An overall efficiency can be decomposed into two stages of efficiencies (Kao & Hwang, 2008), suggesting that we should also evaluate the sub-processes of a firm (Kao & Hwang, 2011). That is, managers should evaluate their firm performance not only from a multidimensional perspective but also from those of its internal processes. As mentioned in the research of Sharma and Modgil (2019), business performance additionally depends on cost reduction of manufacturing operations and improving the firm’s innovative ability. Recently, Hsieh et al. (2020) have applied two-stage data envelopment analysis (DEA) to investigate organizations’ innovation and business performance by investigating the network structures of decision-making units (DMUs).

Conclusion

     This study measures the firm performance of 41 PMNEs from a two-stage perspective, namely R&D efficiency and business performance, by integrating a two-stage network DEA and SOCP technique. Moreover, this study integrates the DEA approach and rough set theory to rank PMNEs. The findings of this research can serve as a reference for managers of PMNEs in their decision-making process. Besides, we examine differences in the ESG scores of the PMNEs among different geographic regions (America, Asia, and Europe). This acts as a guide for investors, managers, and other stakeholders when attempting to move their ESG initiatives further.

     R&D performances in the operation of the observed PMNEs are not attracting enough attention. Alfresa Holdings Corporation is the only efficient PMNE for both R&D efficiency and business performance. North America is significantly the best (worst) region in terms of business performance (R&D efficiency) while Europe is significantly the best (worst) region in terms of R&D efficiency (business performance). From the perspective of ESG performance, European PMNEs significantly have better environmental and social performance than other regions whereas they are the worst concerning governance performance.