Traditional Drug Delivery Systems Research Articles

Nanobots: Revolutionising the Next Generation of Biomedical Technology and Drug Therapy

Abstract: Nanoscale machines called “nanorobots” that were hitherto only futuristic ideas are set to storm healthcare and pharmaceuticals with newer technologies for minimally invasive diagnosis, quick and precise surgeries, and targeted drug delivery, which is challenging to achieve by conventional drug delivery systems. Nanobots can be defined as controllable nano-sized mechanical or electromechanical devices which are easily incorporated into cells and used for a variety of cellular functions like combating bacteria and viruses, disposing away dead cells/tissue at the place of a wound, cell/tissue repair and destruction of cancer cells, and also for transporting drugs to cells. Nanorobots can help avoid the untoward effects of traditional drug delivery systems and ameliorate the efficiency of drug delivery by quickly entering the desired cells without affecting other organs. With the advent of mobile communication, artificial neural networks, and Information Technology, futuristic and more advanced nanobots with artificial intelligence are in the offing. However, the challenges to this revolutionary technology are umpteen, the major concern being their interaction inside the human body. This review explicitly expounds on nanobots and their applications to medicine, biomedical research, and drug delivery.

Ultrasound-guided drug delivery system utilizing piezocatalytic MoS2 nanomaterials for anti-inflammatory therapy

Traditional drug delivery systems lack the potential of controlled drug release, thereby decreasing drug utilization and release efficiency. Herein, a next generation of stimuli-responsive drug delivery platform is designed based on piezocatalytic molybdenum disulfide nanoflowers (MoS2 NFs) which can be triggered by ultrasound (US) stimulation for effective acute inflammation therapy. Under US irradiation, MoS2 NFs undergoes piezocatalysis to generate reactive oxygen species (ROS) owing to piezoelectric polarization, thus releasing loaded anti-inflammatory drug Indomethacin (IND) to the targeted inflammation site. The cumulative release of IND elevated significantly with the increase in the duration for US exposure due to the amplified ROS generation, which displayed a highly controllable nature of the as-designed drug delivery platform. For convenient applications, the IND loaded MoS2 NFs (IND@MoS2 NFs) was functionalized onto commercial dressings and their tunable in-vivo drug release performance was demonstrated in paw edema model. IND@MoS2 NFs upon US irradiation, controllably released IND into the site-specific inflamed paw which significantly inhibited 56 % of paw swelling in 6 h by suppressing the infiltration of neutrophils and expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The highly controllable drug delivery system holds great potential in facilitating personalized, user-friendly theranostic applications with improved patient outcomes.

Recent Advancement of In-situ Gel for the treatment of Ocular disorder

The ocular drug delivery system is very crucial and difficult because the eye is the most sensitive part of the body. The in-situ drug delivery system is the smart way to deliver the drug in an ocular disorder with fewer risk factors. The in-situ drug delivery system promises to give fewer side effects and more effective effects. In the in-situ drug delivery system most of the drugs are formed from natural polymers. The formation of in situ gel is done in a way that they are solid at room temp and gel after it is administered in the eye. The in-situ drug delivery system is the safest system to deliver drugs for ocular disorders. There are many recent advancements in in situ drug delivery systems that are used to treat ocular disorders. innovative polymers and nanotechnologies offer tailored drug delivery effectively improving biocompatibility and biodegradation and reducing systemic side effects. By offering sustained drug release these devices solve problems with traditional drug delivery systems. The review highlights the in-situ gel drug delivery system for the treatment of the ocular disorder.

Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder (ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive dysfunction and an inability to perform daily activities. The progression of AD is associated with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum stress. Presently, various phytomedicines and their bioactive compounds have been identified for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects, the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing to this limitation is the challenges inherent in traditional drug delivery systems, which impede their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted drug solubility and stability, brief duration of action, and a lack of control over drug release. Consequently, these constraints result in diminished bioavailability and insufficient permeability across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability. Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced permeability of the drug in systemic circulation and the brain. Various studies have reported the testing of NE-based phytoconstituents and their bioactives in different animal species, including transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various aspects such as the neuroprotective role of various phytoconstituents, the challenges associated with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various studies involving phytoconstituent-based NE for the treatment of AD are also discussed.

Magnetic-driven hydrogel microrobots for promoting osteosarcoma chemo-therapy with synthetic lethality strategy.

The advancements in the field of micro-robots for drug delivery systems have garnered considerable attention. In contrast to traditional drug delivery systems, which are dependent on blood circulation to reach their target, these engineered micro/nano robots possess the unique ability to navigate autonomously, thereby enabling the delivery of drugs to otherwise inaccessible regions. Precise drug delivery systems can improve the effectiveness and safety of synthetic lethality strategies, which are used for targeted therapy of solid tumors. MYC-overexpressing tumors show sensitivity to CDK1 inhibition. This study delves into the potential of Ro-3306 loaded magnetic-driven hydrogel micro-robots in the treatment of MYC-dependent osteosarcoma. Ro-3306, a specific inhibitor of CDK1, has been demonstrated to suppress tumor growth across various types of cancer. We have designed and fabricated this micro-robot, capable of delivering Ro-3306 precisely to tumor cells under the influence of a magnetic field, and evaluated its chemosensitizing effects, thereby augmenting the therapeutic efficacy and introducing a novel possibility for osteosarcoma treatment. The clinical translation of this method necessitates further investigation and validation. In summary, the Ro-3306-loaded magnetic-driven hydrogel micro-robots present a novel strategy for enhancing the chemosensitivity of MYC-dependent osteosarcoma, paving the way for new possibilities in future clinical applications.

Liposomes as Transformative Tools in Drug Delivery, Therapeutics, and Beyond

Abstract: Abstract: Liposomes are spherical vesicles composed of lipid bilayers that have gained significant attention in the realm of drug delivery and therapeutic applications. They offer several advantages over traditional drug delivery systems, including: -Protection of drugs from degradation and clearance -Enhanced bioavailability - Reduced systemic toxicity - Precise, site-specific drug delivery To elucidate the multifaceted aspects of liposomes, from their fundamental structure and composition to their cutting-edge applications in medicine and biotechnology. This comprehensive review was conducted through a systematic search of relevant literature on liposomes. The search was limited to English-language articles published in the past 10 years. A total of 150 articles were selected for review based on their relevance and impact. The review provides a detailed overview of the following aspects of liposomes: -Structure and composition - Mechanism of action - Targeting strategies - Preparation methods - Biomedical and biotechnological applications Liposomes are a promising drug delivery platform with the potential to revolutionize the treatment of various diseases. Their unique properties, including biocompatibility, versatility, and tunability, render them ideal for encapsulating a wide range of therapeutic agents. The review highlights the significant progress made in liposome research in recent years, paving the way for their translation into clinical practice.

Peptide-Drug Conjugate with Statistically Designed Transcellular Peptide for Psoriasis-Like Inflammation.

Peptide-drug conjugates (PDCs) are a promising class of drug delivery systems that utilize covalently conjugated carrier peptides with therapeutic agents. PDCs offer several advantages over traditional drug delivery systems including enhanced target engagement, improved bioavailability, and increased cell permeability. However, the development of efficient transcellular peptides capable of effectively transporting drugs across biological barriers remains an unmet need. In this study, physicochemical criteria based on cell-penetrating peptides are employed to design transcellular peptides derived from an antimicrobial peptides library. Among the statistically designed transcellular peptides (SDTs), SDT7 exhibits higher skin permeability, faster kinetics, and improved cell permeability in human keratinocyte cells compared to the control peptide. Subsequently, it is found that 6-Paradol (PAR) exhibits inhibitory activity against phosphodiesterase 4, which can be utilized for an anti-inflammatory PDC. The transcellular PDC (SDT7-conjugated with PAR, named TM5) is evaluated in mouse models of psoriasis, exhibiting superior therapeutic efficacy compared to PAR alone. These findings highlight the potential of transcellular PDCs (TDCs) as a promising approach for the treatment of inflammatory skin disorders.

Nanoparticle drug delivery systems responsive to tumor microenvironment: Promising alternatives in the treatment of triple-negative breast cancer.

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

PH-dependent interactions of coacervate-forming histidine-rich peptide with model lipid membranes

Peptide-based liquid droplets (coacervates) produced by spontaneous liquid-liquid phase separation (LLPS), have emerged as a promising class of drug delivery systems due to their high entrapping efficiency and the simplicity of their formulation. However, the detailed mechanisms governing their interaction with cell membranes and cellular uptake remain poorly understood. In this study, we investigated the interactions of peptide coacervates composed of HBpep—peptide derived from the histidine-rich beak proteins (HBPs) of the Humboldt squid—with model cellular membranes in the form of supported lipid bilayers (SLBs). We employed quartz crystal microbalance with dissipation monitoring (QCM-D), neutron reflectometry (NR) and atomistic molecular dynamics (MD) simulations to reveal the nature of these interactions in the absence of fluorescent labels or tags. HBpep forms small oligomers at pH 6 whereas it forms µm-sized coacervates at physiological pH. Our findings reveal that both HBpep oligomers and HBpep-coacervates adsorb onto SLBs at pH 6 and 7.4, respectively. At pH 6, when the peptide carries a net positive charge, HBpep oligomers insert into the SLB, facilitated by the peptide’s interactions with the charged lipids and cholesterol. Importantly, however, HBpep coacervate adsorption at physiological pH, when it is largely uncharged, is fully reversible, suggesting no significant lipid bilayer rearrangement. HBpep coacervates, previously identified as efficient drug delivery vehicles, do not interact with the lipid membrane in the same manner as traditional cationic drug delivery systems or cell-penetrating peptides. Based on our findings, HBpep coacervates at physiological pH cannot cross the cell membrane by a simple passive mechanism and are thus likely to adopt a non-canonical cell entry pathway.

Sodium Chloride Induced pH and Temperature Responsive Biocompatible Hydrogel of Choline Oleate for Transdermal Drug Delivery of Doxorubicin

AbstractNanodrug carriers have various biological and pharmaceutical applications, and among all the transdermal drug delivery is fascinating, specifically for localized medication therapy to a specific diseased organ or limited diseased area of the body, such as breast cancer cells or carcinoma cells. This way the efficacy of drug can be enhanced and its side effect to other healthy organs can be reduced to great extent. To ameliorate the limitations of traditional polymeric drug delivery systems, such as limited quantity and heterogeneity of the loaded drug, we developed a NaCl induced biocompatible gel of wormlike micelles of surface active ionic liquid (SAIL) i. e. choline oleate ([Ch][Ol]). Apart from the pH and temperature responsive mechanical properties, the designed gel also show good skin permeability, biocompatibility, adhesive qualities, stretchability, and viscoelasticity. The gel was tested for encapsulation of anticancer drug doxorubicin (DOX) and its transdermal delivery at pH=7.4 and pH=5.2. This system exhibits tremendous transdermal permeability of DOX and selective release more amount of the drug at 5.2 pH. Hence for localised and targeted delivery of an anticancer drug, this system can be proven to be suitable.

Biohybrid Nanoparticle-Based In Situ Monitoring of In Vivo Drug Delivery.

Nanomaterials have gained huge attention worldwide owing to their unique physicochemical characteristics which enable their applications in the field of biomedicine and drug delivery systems. Although nanodrug delivery systems (NDDSs) have better target specificity and bioavailability than traditional drug delivery systems, their behavior and clearance mechanisms in living subjects remain unclear. In this regard, the importance of bioimaging methods has come to the forefront for investigating the biodistribution of nanocarriers and discovering drug release mechanisms in vivo. In this review, we introduce several examples of biohybrid nanoparticles and their clinical applications, focusing on their advantages and limitations. The various bioimaging methods for monitoring the fate of nanodrugs in biological systems and the future perspectives of NDDSs have also been discussed.

Updates on Novel Treatments for Rheumatoid Arthritis

Chronic joint inflammation is a hallmark of the systemic inflammatory illness known as rheumatoid arthritis (RA), which ultimately causes severe disability and early death. Around 1% of people worldwide are affected by it, and women are 2-3 times more likely to be affected than males. Preclinical RA, genetic influences and environmental influences all have a role in the etiology of the illness. Since there is no recognized treatment for RA, achieving the lowest disease activity and, if possible, recovery remains the key goals of care. The literature on the various RA therapy options, their mechanisms of action, side effects and innovative drug delivery systems that are currently being used for medication administration are highlighted in this review, with non-steroidal anti-inflammatory drug delivery systems receiving the most attention. The most popular medications from each class are reviewed, including corticosteroids, non-steroidal anti-inflammatory medicines (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) and biologics. Traditional medication therapy has various drawbacks, including inadequate bioavailability, first pass metabolism, gastrointestinal enzyme degradation, limited solubility and permeability, food interactions and toxicity. Innovative drug delivery technologies such as microspheres, nanoparticles, dendrimers, liposomes and others, hold great promise since they have been able to overcome the drawbacks of traditional drug delivery systems. The current review compares and contrasts numerous unique drug delivery methods that have been investigated for using anti-rheumatic medications, as well as the benefits of using these novel methods over traditional drug delivery methods.

Transdermal Drug Delivery System

Abstract: A various non-invasive administration have recently emerged as an alternative toconventional needles. Transdermal drug delivery system is most attractive method. The transdermal as route has numerous advantages over the more traditional drug delivery system and they include high bioavailability, absence offirst pass hepatic metabolism, steady drug plasma concentration. and the fact that therapy is noninvasive. TDDS could be applicable in not only Pharmaceuticals but also in the skin industry, including cosmetics. Transdermal drug delivery has made an important contribution to medical practice such as diabetes, hemo rrhoids arthritis, migraine and Schizophrenia treatment, but yet to fully achieve it’s potential in the treatment of Obesity. The adhesive of the transdermal drug delivery system is critical to the safety, efficacy and quality of product

Recent Progress in Phage-Based Nanoplatforms for Tumor Therapy.

Nanodrug delivery systems have demonstrated a great potential for tumor therapy with the development of nanotechnology. Nonetheless, traditional drug delivery systems are faced with issues such as complex synthetic procedures, low reproducibility, nonspecific distribution, impenetrability of biological barrier, systemic toxicity, etc. In recent years, phage-based nanoplatforms have attracted increasing attention in tumor treatment for their regular structure, fantastic carrying property, high transduction efficiency and biosafety. Notably, therapeutic or targeting peptides can be expressed on the surface of the phages through phage display technology, enabling the phage vectors to possess multifunctions. As a result, the drug delivery efficiency on tumor will be vastly improved, thereby enhancing the therapeutic efficacy while reducing the side effects on normal tissues. Moreover, phages can overcome the hindrance of biofilm barrier to elicit antitumor effects, which exhibit great advantages compared with traditional synthetic drug delivery systems. Herein, this review not only summarizes the structure and biology of the phages, but also presents their potential as prominent nanoplatforms against tumor in different pathways to inspire the development of effective nanomedicine.

Liposome-Based Antibacterial Delivery: An Emergent Approach to Combat Bacterial Infections.

The continued emergence and spread of drug-resistant pathogens and the decline in the approval of new antimicrobial drugs pose a major threat to managing infectious diseases, resulting in high morbidity and mortality. Even though a significant variety of antibiotics can effectively cure many bacterial infectious diseases, microbial infections remain one of the biggest global health problems, which may be due to the traditional drug delivery system's shortcomings which lead to poor therapeutic index, low drug absorption, and numerous other drawbacks. Further, the use of traditional antibiotics to treat infectious diseases has always been accompanied by the emergence of multidrug resistance and adverse side effects. Despite developing numerous new antibiotics, nanomaterials, and various techniques to combat infectious diseases, they have persisted as major global health issues. Improving the current antibiotic delivery systems is a promising approach to solving many life-threatening infections. In this context, nanoliposomal systems have recently attracted much attention. Herein, we attempt to provide a concise summary of recent studies that have used liposomal nanoparticles as delivery systems for antibacterial medicines. The minireview also highlights the enormous potential of liposomal nanoparticles as antibiotic delivery systems. The future of these promising approaches lies in developing more efficient delivery systems by precisely targeting bacterial cells with antibiotics with minimum cytotoxicity and high bacterial combating efficacy.

Improved in vitro biocompatibility and cytoplasmic localization of gold nanoparticles and graphene oxide nanosheets assessed using confocal microscopy

Nanomaterial-based delivery platforms have indeed revolutionized drug delivery systems in recent years. These platforms, which are based on various types of nanoparticles, offer several advantages over traditional drug delivery systems. Therefore, during this work, we synthesized gold nanoparticles (GNPs) and graphene oxide (GO) as representative nanomaterials and assessed their biocompatibility and cytoplasmic localization in vitro. Structural characterization of the prepared nanoparticles was performed by using different techniques. For instance, laser diffraction spectrometry using a Nano-ZS Zetasizer was used to determine the particles size, and Zeta potential. High-resolution transmission electron microscopy (HR-TEM) were utilized to evaluate Particle sizes and morphologies of the prepared nanoparticles. Additionally, the chemical structure of the prepared nanoparticles was assessed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The effects of the different concentrations of GNPs and GO nanosheets on cell viability and proliferation were evaluated by WST-1 cell proliferation assays. Ultimately, in vitro studies were performed by confocal microscopy to characterize the cellular uptake of the prepared nanoparticles. The net results of this study suggest that both nanomaterials showed a cytoplasmic entry without penetrating the nucleus. They may be useful for slow drug release as well as photothermal and photodynamic therapy using a low-powered laser or IR radiation.

Exosome-Based Drug Delivery: Translation from Bench to Clinic.

Exosome-based drug delivery is emerging as a promising field with the potential to revolutionize therapeutic interventions. Exosomes, which are small extracellular vesicles released by various cell types, have attracted significant attention due to their unique properties and natural ability to transport bioactive molecules. These nano-sized vesicles, ranging in size from 30 to 150 nm, can effectively transport a variety of cargoes, including proteins, nucleic acids, and lipids. Compared to traditional drug delivery systems, exosomes exhibit unique biocompatibility, low immunogenicity, and reduced toxicity. In addition, exosomes can be designed and tailored to improve targeting efficiency, cargo loading capacity, and stability, paving the way for personalized medicine and precision therapy. However, despite the promising potential of exosome-based drug delivery, its clinical application remains challenging due to limitations in exosome isolation and purification, low loading efficiency of therapeutic cargoes, insufficient targeted delivery, and rapid elimination in circulation. This comprehensive review focuses on the transition of exosome-based drug delivery from the bench to clinic, highlighting key aspects, such as exosome structure and biogenesis, cargo loading methods, surface engineering techniques, and clinical applications. It also discusses challenges and prospects in this emerging field.

Applications of MOFs in Drug Delivery

The main research focus of this article is the application of Metal-Organic Frameworks (MOFs) in drug delivery applications. The review primarily concentrates on the methods used for loading drugs into MOFs, their response to stimuli, potential applications, and limitations. The article begins with discussing the limitations of traditional drug delivery systems and introduces MOFs as a potential solution to these limitations. The drug loading strategy section describes the three main methods for loading drugs into MOFs, including their respective benefits and drawbacks. The stimulus response release program section explores various stimuli that can trigger drug release from MOFs, including physical, chemical, and biological factors, and provides examples of how MOFs can respond to these stimuli. The section on application and challenges provides an overview of current studies exploring the potential of MOFs in biomedical applications, including cancer therapy, antibacterial therapy, and anti-inflammatory therapy, while also highlighting the key challenges facing MOFs research, such as biocompatibility and toxicity. Finally, the article concludes by offering prospects for future developments in MOFs research. This review article provides a significant resource for drug delivery researchers and practitioners who wish to investigating the possibility of utilizing MOFs as novel drug delivery vehicles.

Cancer Drug Delivery Systems Using Bacterial Toxin Translocation Mechanisms.

Recent advances in targeted cancer therapy hold great promise for both research and clinical applications and push the boundaries in finding new treatments for various currently incurable cancers. However, these therapies require specific cell-targeting mechanisms for the efficient delivery of drug cargo across the cell membrane to reach intracellular targets and avoid diffusion to unwanted tissues. Traditional drug delivery systems suffer from a limited ability to travel across the barriers posed by cell membranes and, therefore, there is a need for high doses, which are associated with adverse reactions and safety concerns. Bacterial toxins have evolved naturally to specifically target cell subtypes via their receptor binding module, penetrating the cell membrane efficiently through the membrane translocation process and then successfully delivering the toxic cargo into the host cytosol. They have, thus, been harnessed for the delivery of various drugs. In this review, we focus on bacterial toxin translocation mechanisms and recent progress in the targeted delivery systems of cancer therapy drugs that have been inspired by the receptor binding and membrane translocation processes of the anthrax toxin protective antigen, diphtheria toxin, and Pseudomonas exotoxin A. We also discuss the challenges and limitations of these studies that should be addressed before bacterial toxin-based drug delivery systems can become a viable new generation of drug delivery approaches in clinical translation.