Synthetic Delivery Systems Research Articles

Lipid-Based Nanoparticles in Delivering Bioactive Compounds for Improving Therapeutic Efficacy.

In recent years, due to their distinctive and adaptable therapeutic effects, many natural bioactive compounds have been commonly used to treat diseases. Their limited solubility, low bioavailability, inadequate gastrointestinal tract stability, high metabolic rate, and shorter duration of action limited their pharmaceutical applications. However, those can be improved using nanotechnology to create various drug delivery systems, including lipid-based nanoparticles, to adjust the compounds' physicochemical properties and pharmacokinetic profile. Because of the enormous technical advancements made in the fundamental sciences and the physical and chemical manipulation of individual atoms and molecules, the subject of nanotechnology has experienced revolutionary growth. By fabricating certain functionalized particles, nanotechnology opens an innovative horizon in research and development for overcoming restrictions, including traditional medication administration systems. Nanotechnology-driven bioactive compounds are certain to have a high impact and clinical value for current and future uses. Lipid-based nanotechnologies were shown to deliver a range of naturally occurring bioactive compounds with decent entrapment potential and stability, a successfully controlled release, increased bioavailability, and intriguing therapeutic activity. This review outlines bioactive compounds such as paclitaxel, curcumin, rhodomyrtone, quercetin, kaempferol, resveratrol, epigallocatechin-3-gallate, silymarin, and oridonin, fortified within either a natural or synthetic lipid-based drug delivery system based on nanotechnology and their evaluation and clinical considerations.

A vivid outline demonstrating the benefits of exosome-mediated drug delivery in CNS-associated disease environments

The efficacy of drug delivery mechanisms has been improvised with time for different therapeutic purposes. In most cases, nano-sized delivery systems have been modeled over decades for the on-target applicability of the drugs. The use of synthetic drug delivery materials has been a common practice, although research has now focussed more on using natural vehicles, to avoid the side effects of synthetic delivery systems and easy acceptance by the body. Exosome is such a natural nano-sized vehicle that exceeds the efficiency of many natural vehicles, for being immune-friendly, due to its origin. Unlike, other natural drug delivery systems, exosomes are originated within the body's cells, and from there, they happen to travel through the extracellular matrices into neighboring cells. This capacity of exosomes has made them an efficient drug delivery system over recent years and now a large number of researches have been carried out to develop exosomes as natural drug delivery vehicles. Several experimental strategies have been practiced in this regard which have shown that exosomes are exclusively capable of carrying drugs and they can also be used in targeted delivery, for which they efficiently can reach and release the drug at their target cells for consecutive effects. One of the most interesting features of exosomes is they can cross the blood-brain barrier (BBB) in the body and hence, for the disease where other delivery vehicles are incapable of reaching the destination of the drug, exosomes can overcome the hurdle. This review particularly, focuses on the different aspects of using exosomes as a potential nano-sized drug delivery system for some of the severe diseases associated with the central nervous system of the human body.

Design and Evaluation of Synthetic Delivery Formulations for Peptide-Based Cancer Vaccines.

With the recent advances in neoantigen identification, peptide-based cancer vaccines offer substantial potential in the field of immunotherapy. However, rapid clearance, low immunogenicity, and insufficient antigen-presenting cell (APC) uptake limit the efficacy of peptide-based cancer vaccines. This review explores the barriers hindering vaccine efficiency, highlights recent advancements in synthetic delivery systems, and features strategies for the key delivery steps of lymph node (LN) drainage, APC delivery, cross-presentation strategies, and adjuvant incorporation. This paper also discusses the design of preclinical studies evaluating vaccine efficiency, including vaccine administration routes and murine tumor models.

Recent advances in polymeric microparticle-based drug delivery systems for knee osteoarthritis treatment.

Due to the poor bioavailability and high joint clearance of drugs, sustained delivery of therapeutic agents has proven difficult in the treatment of osteoarthritis (OA). Intra-articular (IA) drug delivery strategy is an attractive option for enhancing OA patients' prognosis, for which various polymer materials have been used as drug carriers due to their attractive delivery properties, to slow or even reverse the progress of OA by prolonging the duration of therapeutic agent residence in the joint. This article focuses on the recent developments in natural and synthetic polymer-based microsphere drug delivery systems for treating knee osteoarthritis. It evaluates the translational potential of some novel formulations for clinical application.

NANOENCAPSULATION OF LUTEOLIN: ENHANCING BIOAVAILABILITY AND MEDICINAL BENEFITS

Luteolin is a naturally occurring chemical widely found in plants ranging from Bryophyta to Magnoliophyta. It can be obtained from several dietary sources such as carrots, olive oil, celery, spinach, oregano, and, fossils of some organisms such as Celtis and Ulmus dating back 36 to 25 million years. It is synthesized by the Shikimate pathway. The major qualities and therapeutic benefits of luteolin include cytoprotective abilities, Antioxidant, Anti-inflammatory, Anticancer, Antidepressant, Antidiabetic, Antiallergic, Reactive Oxygen Species Scavenging and High radical scavenging. The antioxidant and Reactive Oxygen Species scavenging activity of luteolin aids in treating and curing inflammatory skin processes. It has been proven to act as a therapeutic drug with a wide spectrum of scope in the prevention and treatment of a vast range of malignant and benign cancers, extending from bladder cancer to breast cancer and from oral cancer to glioblastoma, which is achieved by its anticancer, antioxidant properties and cytoprotective abilities. Apart from its anticancer properties, it has a great scope in the restoration from neuropsychiatric disease and high-level fatigue due to Long COVID syndrome-associated brain fog and Chemo fog. The poor solubility and low bioavailability of luteolin limit its use in food and medicine. Synthetic and Natural polymer-based delivery systems have been developed to improve its stability and bioavailability. This review will highlight recent research on its nanoencapsulation and provide more information on luteolin to help readers have a better grasp of the compound's medicinal benefits.

Synthetic Outer Membrane Vesicles Bearing Tn Antigen

AbstractN‐Alkyl‐thio glycolipids (TGL) are proposed as fundamental components in the production of synthetic outer membrane vesicles (S‐OMVs). A small but representative library of glycolipids was prepared by thiol‐ene coupling (TEC), using unprotected thiols in acceptable to good yields (63‐96 %). Multilamellar giant vesicles (GVs) of varying sizes were assembled from mixtures of TGL and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphate (POPC). Our results mark an important advancement for the development of synthetic anticancer vaccines, supramolecular adjuvants and drug delivery systems based on glycolipid/phospholipid formulations (10 % mol/mol in 0.1 mm solution).

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.

Nano-delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives.

Epilepsy is a common chronic neurological disorder caused by aberrant neuronal electrical activity. Antiseizure medications (ASMs) are the first line of treatment for people with epilepsy (PWE). However, their effectiveness may be limited by their inability to cross the blood-brain barrier (BBB), among many other potential underpinnings for drug resistance in epilepsy. Therefore, there is a need to overcome this issue and, hopefully, improve the effectiveness of ASMs. Recently, synthetic nanoparticle-based drug delivery systems have received attention for improving the effectiveness of ASMs due to their ability to cross the BBB. Furthermore, exosomes have emerged as a promising generation of drug delivery systems because of their potential benefits over synthetic nanoparticles. In this narrative review, we focus on various synthetic nanoparticles that have been studied to deliver ASMs. Furthermore, the benefits and limitations of each nano-delivery system have been discussed. Finally, we discuss exosomes as potentially promising delivery tools for treating epilepsy.

Targeted drug delivery system inspired by macropinocytosis.

Macropinocytosis is a widely-observed and evolutionarily-conserved endocytic process found in the eukaryotic cells. In comparison to other endocytic routes, macropinocytosis allows for the internalization of greater quantities of fluid-phase drugs, making it an attractive avenue for drug delivery. Recent evidence showed that various drug delivery systems can be internalized through macropinocytosis. Utilizing macropinocytosis may therefore provide a new avenue for targeted intracellular delivery. In this review, we provide an overview into the origins and distinctive properties of macropinocytosis, summarize the roles of macropinocytosis under healthy and pathological settings. Furthermore, we highlight the biomimetic and synthetic drug delivery systems that employ macropinocytosis as the primary internalization mechanism. To facilitate the clinical applications of these drug delivery systems, additional research can be conducted to enhance the cell-type selectivity of macropinocytosis, the control of drug release at the target, and the prevention of potential toxicity. The rapidly emerging field of macropinocytosis-based targeted drug delivery and therapies holds great potential to drastically increase the efficiency and specificity of drug delivery.

Synthetic and Natural Polymeric Drug Delivery Systems - A Comprehensive Overview of Polycaprolactone and Glucan Particles

The small size and large surface area of nano and microparticles are interesting properties for drug delivery, hypothetically capable of overcoming some limitations of conventional therapeutic medicine and diagnostic agents. Although their features are highly influenced by the polymer characteristics, these particles are known for encapsulating high amounts of drugs, improving their stability and bioavailability and enabling different administration routes. Among synthetic polymers, polycaprolactone (PCL) nanoparticles are widely studied in drug delivery due to the polymer excellent biocompatibility and degradability and for its ability to blend with other polymers. On its turn, among natural polymers, glucan has been emerging as a promising candidate for drug delivery particularly due to structure forming abilities and its immunomodulatory effects. Under the safe-by-design approach for the development of polymeric particles, this review encloses a comprehensive summary of production methods, physicochemical characteristics and immunotoxicity profiles of PCL and glucan particles developed for drug delivery.

Innovation in the Development of Synthetic and Natural Ocular Drug Delivery Systems for Eye Diseases Treatment: Focusing on Drug-Loaded Ocular Inserts, Contacts, and Intraocular Lenses

Nowadays, ocular drug delivery still remains a challenge, since the conventional dosage forms used for anterior and posterior ocular disease treatments, such as topical, systemic, and intraocular administration methods, present important limitations mainly related to the anatomical complexity of the eye. In particular, the blood-ocular barrier along with the corneal barrier, ocular surface, and lacrimal fluid secretion reduce the availability of the administered active compounds and their efficacy. These limitations have increased the need to develop safe and effective ocular delivery systems able to sustain the drug release in the interested ocular segment over time. In the last few years, thanks to the innovations in the materials and technologies employed, different ocular drug delivery systems have been developed. Therefore, this review aims to summarize the synthetic and natural drug-loaded ocular inserts, contacts, and intraocular lenses that have been recently developed, emphasizing the characteristics that make them promising for future ocular clinical applications.

Biodistribution of therapeutic extracellular vesicles

The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their unique ability to transfer macromolecules across cells and biological barriers has made them a rising star in drug delivery. Mounting evidence suggests that EVs can be explored as efficient drug delivery vehicles for a range of therapeutic macromolecules. In contrast to many synthetic delivery systems, these vesicles appear exceptionally well tolerated in vivo. This tremendous development in the therapeutic application of EVs has been made through technological advancement in labelling and understanding the in vivo biodistribution of EVs. Here in this review, we have summarised the recent findings in EV in vivo pharmacokinetics and discussed various biological barriers that need to be surpassed to achieve tissue-specific delivery.

Genetically engineered bacteria: a new frontier in targeted drug delivery.

Genetically engineered bacteria (GEB) have shown significant promise to revolutionize modern medicine. These engineered bacteria with unique properties such as enhanced targeting, versatility, biofilm disruption, reduced drug resistance, self-amplification capabilities, and biodegradability represent a highly promising approach for targeted drug delivery and cancer theranostics. This innovative approach involves modifying bacterial strains to function as drug carriers, capable of delivering therapeutic agents directly to specific cells or tissues. Unlike synthetic drug delivery systems, GEB are inherently biodegradable and can be naturally eliminated from the body, reducing potential long-term side effects or complications associated with residual foreign constituents. However, several pivotal challenges such as safety and controllability need to be addressed. Researchers have explored novel tactics to improve their capabilities and overcome existing challenges, including synthetic biology tools (e.g., clustered regularly interspaced short palindromic repeats (CRISPR) and bioinformatics-driven design), microbiome engineering, combination therapies, immune system interaction, and biocontainment strategies. Because of the remarkable advantages and tangible progress in this field, GEB may emerge as vital tools in personalized medicine, providing precise and controlled drug delivery for various diseases (especially cancer). In this context, future directions include the integration of nanotechnology with GEB, the focus on microbiota-targeted therapies, the incorporation of programmable behaviors, the enhancement in immunotherapy treatments, and the discovery of non-medical applications. In this way, careful ethical considerations and regulatory frameworks are necessary for developing GEB-based systems for targeted drug delivery. By addressing safety concerns, ensuring informed consent, promoting equitable access, understanding long-term effects, mitigating dual-use risks, and fostering public engagement, these engineered bacteria can be employed as promising delivery vehicles in bio- and nanomedicine. In this review, recent advances related to the application of GEB in targeted drug delivery and cancer therapy are discussed, covering crucial challenging issues and future perspectives.

Chemical Approaches to Synthetic Drug Delivery Systems for Systemic Applications.

Poor water solubility and low bioavailability of active pharmaceutical ingredients (APIs) are major causes of friction in the pharmaceutical industry and represent a formidable hurdle for pharmaceutical drug development. Drug delivery remains the major challenge for the application of new small-molecule drugs as well as biopharmaceuticals. The three challenges for synthetic delivery systems are: (i) controlling drug distribution and clearance in the blood; (ii) solubilizing poorly water-soluble agents, and (iii) selectively targeting specific tissues. Although several polymer-based systems have addressed the first two demands and have been translated into clinical practice, no targeted synthetic drug delivery system has reached the market. This Review is designed to provide a background on the challenges and requirements for the design and translation of new polymer-based delivery systems. This report will focus on chemical approaches to drug delivery for systemic applications.

Chemische Ansätze für synthetische Wirkstofftransportsysteme für systemische Anwendungen

AbstractSchlechte Wasserlöslichkeit und geringe Bioverfügbarkeit von pharmazeutischen Wirkstoffen (APIs) sind die Hauptursache für Verzögerungen in der pharmazeutischen Industrie und stellen eine große Hürde für die Entwicklung neuer Arzneimittel dar. Der Transport von Arzneimitteln ist nach wie vor die größte Herausforderung für die Anwendung niedermolekularer Medikamente und Biopharmazeutika. Die drei Herausforderungen für synthetische Transportsysteme sind: (i) Kontrolle über die Wirkstoffverteilung und Clearance im Blut, (ii) Solubilisierung schlecht wasserlöslicher Wirkstoffe und (iii) selektive Akkumulation in bestimmten Geweben. Obwohl viele Polymer‐basierte Systeme die ersten beiden Anforderungen erfüllen und in die klinische Praxis umgesetzt wurden, hat bisher noch kein zielgerichtetes, synthetisches Abgabesystem den Markt erreicht. Dieser Aufsatz soll einen Überblick über die Herausforderungen und Anforderungen zur Entwicklung und Umsetzung neuer Polymer‐basierter Darreichungssysteme geben. Hauptaugenmerk liegt hierbei auf den chemischen Ansätzen für die Darreichung von Wirkstoffen für systemische Anwendungen.

Efficient Gene Delivery of Tailored Amphiphilic Polypeptides by Polyplex Surfing.

Within this study, an amphiphilic and potentially biodegradable polypeptide library based on poly[(4-aminobutyl)-l-glutamine-stat-hexyl-l-glutamine] [P(AB-l-Gln-stat-Hex-l-Gln)] was investigated for gene delivery. The influence of varying proportions of aliphatic and cationic side chains affecting the physicochemical properties of the polypeptides on transfection efficiency was investigated. A composition of 40 mol% Hex-l-Gln and 60 mol % AB-l-Gln (P3) was identified as best performer over polypeptides with higher proportions of protonatable monomers. Detailed studies of the transfection mechanism revealed the strongest interaction of P3 with cell membranes, promoting efficient endocytic cell uptake and high endosomal release. Spectrally, time-, and z-resolved fluorescence microscopy further revealed the crucial role of filopodia surfing in polyplex-cell interaction and particle internalization in lamellipodia regions, followed by rapid particle transport into cells. This study demonstrates the great potential of polypeptides for gene delivery. The amphiphilic character improves performance over cationic homopolypeptides, and the potential biodegradability is advantageous toward other synthetic polymeric delivery systems.

Biotherapy using Sperm Cell-oriented Transportation of Therapeutics in Female Reproductive Tract Cancer.

Female reproductive tract cancers like ovarian, cervical, vaginal, etc. have led to a serious concern for reproductive health as well as an increase in physical and psychological stresses amongst women. Various conventional techniques like surgery, radiation and chemotherapy are employed but possess limitations such as organ toxicity, infection, nausea, vomiting, etc. Also, several nanotechnology-based synthetic vehicle delivery systems like liposomes, nanoparticles, etc. are used but they lack targeting efficiency that results in poor propulsion and control. Therefore, there is a need for naturally-driven drug carriers to overcome such limitations. Sperm-based drug delivery is the new area for targeted delivery that offers self-propulsion to tumor sites, higher biocompatibility, longer lifespan and increased tissue penetration with enhanced localization. Drug-loaded sperm cells are harnessed with micro/nanomotor that will guide them to the intended target site. The critical analysis of the sperm-based drug delivery system was executed and summarized along with the current challenges. This article deals with the art of delivering the anticancer drug to female reproductive cancer sites with proof-of-concept-based research data and critical discussion on challenges in formulating the sperm-based delivery with a future perspective.

Different Sourced Extracellular Vesicles and Their Potential Applications in Clinical Treatments.

Extracellular vesicles (EVs) include a heterogeneous group of natural cell-derived nanostructures that are increasingly regarded as promising biotherapeutic agents and drug delivery vehicles in human medicine. Desirable intrinsic properties of EVs including the ability to bypass natural membranous barriers and to deliver their unique biomolecular cargo to specific cell populations position them as fiercely competitive alternatives for currently available cell therapies and artificial drug delivery platforms. EVs with distinct characteristics can be released from various cell types into the extracellular environment as a means of transmitting bioactive components and altering the status of the target cell. Despite the existence of a large number of preclinical studies confirming the therapeutic efficacy of different originated EVs for treating several pathological conditions, in this review, we first provide a brief overview of EV biophysical properties with an emphasis on their intrinsic therapeutic benefits over cell-based therapies and synthetic delivery systems. Next, we describe in detail different EVs derived from distinct cell sources, compare their advantages and disadvantages, and recapitulate their therapeutic effects on various human disorders to highlight the progress made in harnessing EVs for clinical applications. Finally, knowledge gaps and concrete hurdles that currently hinder the clinical translation of EV therapies are debated with a futuristic perspective.

Dual responsive molecularly imprinted polymers based on UiO-66-DOX for selective targeting tumor cells and controlled drug release

The preparation of synthetic drug delivery systems free of antibody modifications that can effectively recognize tumor sites and control drug delivery is essential for cancer therapy. In this study, UiO-66 metal–organic framework (MOF) modified with amino and phenylboronic acid groups was used as substrate to load the anti-cancer drug doxorubicin (DOX). Then a molecularly imprinted polymer (UiO-66-DOX@MIP) with sialic acid (SA) as the template molecule was further prepared on the surface of the synthesized nanoparticles using surface molecular imprinting technique (MIT). This polymer combines the excellent properties of UiO-66 and molecularly imprinted polymer (MIP). It was simple to prepare, economical and easy to obtain, and had a regular morphology. UiO-66-DOX@MIP containing molecularly imprinted binding sites that match the template molecule SA, could specifically recognize target tumor cells. The imprinted layer prevented drug leakage in normal body fluids while degrading and drug release under tumor microenvironment, with pH and glutathione (GSH) dual-responsive drug release properties. The UiO-66-DOX@MIP showed excellent biocompatibility and great cellular uptake efficiency to cancer cells without influence of interfering substances.

Extracellular Vesicle-Based Hybrid Systems for Advanced Drug Delivery.

The continuous technological advancement of nanomedicine has enabled the development of novel vehicles for the effective delivery of therapeutic substances. Synthetic drug delivery systems are nano-sized carriers made from various materials that can be designed to deliver therapeutic cargoes to cells or tissues. However, rapid clearance by the immune system and the poor targeting profile of synthetic drug delivery systems are examples of the pressing obstacles faced in nanomedicine, which have directed the field toward the development of alternative strategies. Extracellular vesicles (EVs) are nanoscale particles enclosed by a protein-rich lipid bilayer; they are released by cells and are considered to be important mediators of intercellular communication. Owing to their natural composition, EVs have been suggested to exhibit good biocompatibility and to possess homing properties to specific cell types. Combining EVs with synthetic nanoparticles by defined hybridization steps gives rise to a novel potential drug delivery tool, i.e., EV-based hybrid systems. These novel therapeutic vehicles exhibit potential advantageous features as compared to synthetic drug delivery systems such as enhanced cellular uptake and cargo delivery, immuno-evasive properties, capability of crossing biological barriers, and tissue targeting profile. Here, we provide an overview of the various strategies practiced to produce EV-based hybrid systems and elucidate those advantageous features obtained by synthetic drug delivery systems upon hybridization with EVs.