Delivery System Research Articles

Trends on Novel Targets and Nanotechnology-Based Drug Delivery System in the Treatment of Parkinson's disease: Recent Advancement in Drug Development.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that impacts a significant portion of the population. Despite extensive research, an effective cure for PD remains elusive, and conventional pharmacological treatments often face limitations in efficacy and management of symptoms. There has been a lot of discussion about using nanotechnology to increase the bioavailability of small- molecule drugs to target cells in recent years. It is possible that PD treatment might become far more effective and have fewer side effects if medication delivery mechanisms were to be improved. Potential alternatives to pharmacological therapy for molecular imaging and treatment of PD may lie in abnormal proteins such as parkin, α-synuclein, leucine-rich repeat serine and threonine protein kinase 2. Published research has demonstrated encouraging outcomes when nanomedicine-based approaches are used to address the challenges of PD therapy. So, to address the present difficulties of antiparkinsonian treatment, this review outlines the key issues and limitations of antiparkinsonian medications, new therapeutic strategies, and the breadth of delivery based on nanomedicine. This review covers a wide range of subjects, including drug distribution in the brain, the efficacy of drug-loaded nano-carriers in crossing the blood-brain barrier, and their release profiles. In PD, the nano-carriers are also used. Novel techniques of pharmaceutical delivery are currently made possible by vesicular carriers, which eliminate the requirement to cross the blood-brain barrier (BBB).

Necroptosis and autophagy in cisplatinum-triggered nephrotoxicity: Novel insights regarding their prognostic and diagnostic potential

Necroptosis is an innovative class of programmed autophagy (Atg) and necrosis; considered as a type of homeostatic housekeeping machinery that have observed an escalating concern due to its power in alleviating Cisplatinum-induced nephrotoxicity. This article elucidated in details the prospective role of both autophagy and necroptosis on Cisplatinum-triggered nephrotoxicity and investigating more potent therapy via lactoferrin and Ti-NPS conjugation. Cisplatinum is a commonly used chemotherapeutic drug; one of the limiting adverse actions of cisplatinum is renal toxicity. Upon cisplatinum administration, autophagy is highly stimulated in the kidney to shield against nephrotoxicity. Atg is a lysosomal degradation process which discards detorirated proteins to retain cell homeostasis. This article summarizes necroptosis progress in reconizing cisplatinum nephrotoxicity and debates how this progress can help in discovering more potent therapy via lactoferrin and Ti-NPS conjugation via monitoring autophagy and apoptotic biomarkers X-box-binding protein 1 (XBP), C/EBP homologous protein (CHOP), hypoxanthine phosphoribosyltransferase-1 (HPRT), FKBP prolyl isomerase 1B (FKBP), Cellular myelocytomatosis oncogene (C-myc), tumor suppressor gene (P53) and tumor necrosis factor (TNF-α). Cisplatinum nephrotoxicity was conducted in rat model via an oral dose of (2mg/kg BW) for one month furthermore a comparative study was conducted among TiNPs-loaded Cisplatinum and Lactoferrin loaded Cisplatinum. Loaded drug delivery system counteracted Cisplatinum triggered nephrotoxicity via controlling autophagy and apoptotic XBP, CHOP, HPRT, FKBP, C-myc, P53 and TNF-α signaling pathway.

A Comprehensive Review on Prospects of Polymeric Nanoparticles for Treatment of Diabetes Mellitus: Receptors-Ligands, In vitro & In vivo Studies.

As per International Diabetes Federation Report 2022, worldwide diabetes mellitus (DM) caused 6.7M moralities and ~537M adults suffering from diabetes mellitus. It is a chronic condition due to β-cell destruction or insulin resistance that leads to insulin deficiency. This review discusses Type-1 DM and Type-2 DM pathophysiology in detail, with challenges in management and treatment. The toxicity issues of conventional drugs and insulin injections are complex to manage. Thus, there is a need for technological intervention. In recent years, nanotechnology has found a fruitful advancement of novel drug delivery systems that might potentially increase the efficacy of anti-diabetic drugs. Amongst nano-formulations, polymeric nanoparticles have been studied to enhance the bioavailability and efficacy of anti-diabetic drugs and insulin. In the present review, we summarized polymeric nanoparticles with different polymers utilized to deliver anti-diabetic drugs with in vitro and in vivo studies. Furthermore, this review also includes the role of receptors and ligands in diabetes mellitus and the utilization of receptor-ligand interaction to develop targeted nanoparticles. Additionally, we discussed the utility of nanoparticles for the delivery of phytoconstituents which aids in protecting the oxidative stress generated during diabetes mellitus. Atlast, this article also comprises of numerous patents that have been filed or granted for the delivery of antidiabetic and anticancer molecules for the treatment of diabetes mellitus and pancreatic cancer.

In Situ Photo Responsive Biodegradable Nanoparticle Forming Intrauterine Implant for Drug Delivery to Treat Ovarian Diseases: A Rationale-based Review.

Ovarian disease constitutes various types of endocrine disorders, such as polycystic ovarian syndrome (PCOS), ovarian cancer, premature ovarian failure, ovarian endometriosis, and ovarian cysts. The prevalence of ovarian-related diseases is highly vulnerable in the world. The utility of various drug delivery systems for ovarian diseases has resulted in varied success. Moreover, most of them lead to severe adverse effects and are incapable of ameliorating the signs and symptoms of the condition. Intrauterine devices (IUDs) have positioned themselves as a mechanism to deliver the drug for various ovarian-related diseases. Thereby avoiding various stability-related issues arising due to various physiological barriers of the female reproductive tract. However, the use of intrauterine devices for drug delivery to the ovaries has not been fully explored. This is attributed to the fact that they cause cysts in the ovaries and skepticism among patients and physicians. Photo-sensitive devices are an appealing approach for managing disorders affecting the ovaries. Photo-sensitive in situ forming intrauterine implants (IUIs) have several advantages, including simplicity in application, reduced invasiveness, as well as improved site-specific drug release control. Polymeric nanoparticles (PNPs) loaded with a drug may be a suitable choice to provide sustained release, alter the pharmacokinetics, and reduce the dose and dosing frequency. The current manuscript hypothesizes the utility of a PNP-loaded biodegradable photo-responsive intrauterine implantable device as an alternate novel strategy for ameliorating ovarian-related diseases.

PLGA Nanoparticles as New Drug Delivery Systems in Leishmaniasis Chemotherapy: A Review of Current Practices.

Although leishmaniasis is one of the most common parasitic diseases, its traditional treatments suffer from some serious problems. To solve such issues, we can take advantage of the effective nanoparticle-based approaches to deliver anti-leishmanial agents into leishmania-infected macrophages either using passive targeting or using macrophagerelated receptors. Despite the high potential of nanotechnology, Liposomal Amphotericin B (AmBisome®) is the only FDA-approved nanoparticle-based anti-leishmanial therapy. In an effort to find more anti-leishmanial nano-drugs, this 2011-2021 review study aimed to investigate the in-vivo and in-vitro effectiveness of poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) in the delivery of some traditional anti-leishmanial drugs. Based on the results, PLGA-NPs could improve solubility, controlled release, trapping efficacy, bioavailability, selectivity, and mucosal penetration of the drugs, while they decreased resistance, dose/duration of administration and organotoxicity of the agents. However, none of these nano-formulations have been able to enter clinical trials so far. We summarized the data about the common problems of anti-leishmanial agents and the positive effects of various PLGA nano-formulations on reducing these drawbacks under both in-vitro and in-vivo conditions in three separate tables. Overall, this study proposes two AmB-loaded PLGA with a 99% reduction in parasite load as promising nanoparticles for further studies.

Synthesis and Biological Evaluation of Gold Nanoparticles Drug Delivery System as Anti-Rheumatoid Arthritis Agents

Synthesis and Biological Evaluation of Gold Nanoparticles Drug Delivery System as Anti-Rheumatoid Arthritis Agents

ROS responsive nanozyme loaded with STING silencing for the treatment of sepsis-induced acute lung injury

Acute lung injury (ALI) is a common complication of sepsis and a leading cause of mortality in septic patients. Studies indicate that STING may play a crucial role in the pathogenesis of sepsis-induced ALI by interacting with the PARP-1/NLRP3 pathway. Therefore, targeting STING inhibition has potential as a novel therapeutic strategy for ALI. However, effective inhibition remains challenging due to the widespread expression of STING across various tissues. In this study, we developed a nanozyme-based drug delivery system, DSPE-TK-mPEG-MnO2@siSTING (abbreviated as DTmM@siSTING), using DSPE-TK-mPEG-MnO2 as the carrier, and characterized it via scanning electron microscopy, dynamic light scattering, nanoparticle size analysis, and gel electrophoresis. To evaluate the therapeutic effects of DTmM@siSTING, an in vitro ALI cell model and an in vivo ALI mouse model were established, assessing the nanozyme's impact on ROS levels, inflammatory responses, and the PARP-1/NLRP3 pathway in sepsis-induced ALI. Results demonstrated that DTmM@siSTING exhibited good physiological stability. In vitro, DTmM@siSTING significantly reduced ROS levels, myeloperoxidase activity, and expression of inflammatory cytokines, while also inhibiting PARP-1/NLRP3 pathway activation. In vivo experiments further revealed that DTmM@siSTING effectively delivered siSTING to the lungs, mitigating sepsis-induced ALI and associated inflammatory responses. Additionally, DTmM@siSTING displayed excellent biocompatibility. In summary, our findings suggest that DTmM@siSTING significantly enhances the therapeutic efficacy of siSTING, alleviating ALI by inhibiting ROS production, inflammatory responses, and activation of the PARP-1/NLRP3 pathway. This novel approach presents a promising therapeutic avenue for sepsis-induced ALI.

Ex vivo delivery of dsRNA targeting ryanodine receptors for control of Tuta absoluta.

RNA interference (RNAi) is an endogenous eukaryote viral defence mechanism representing a unique form of post-transcriptional gene silencing. Owing to its high specificity, this technology is being developed for use in dsRNA-based biopesticides for control of pest insects. Whilst many lepidopteran species are recalcitrant to RNAi, Tuta absoluta, a polyphagous insect responsible for extensive crop damage, is sensitive. Ryanodine receptors (RyRs) are intracellular calcium channels regulating calcium ion (Ca2+) release. The chemical pesticide class of diamides functions agonistically against lepidopteran RyR, resulting in uncontrolled Ca2+ release, feeding cessation and death. Resistance to diamides has emerged in T. absoluta, derived from RyR point mutations. RNAi was used to target RyR transcripts of T. absoluta. Data presented here demonstrate the systemic use of exogenous T. absoluta RyR-specific (TaRy) dsRNA in tomato plants (Solanum lycopersicum) to significantly downregulate expression of the target gene, resulting in significant insect mortality and reduced leaf damage. Using a leaflet delivery system, daily dosing of 3 μg TaRy dsRNA for 72 h resulted in 50% downregulation of the target gene and 50% reduction in tomato leaf damage. Corrected larval mortality and adult emergence were reduced by 38% and 33%, respectively. TaRy dsRNA demonstrated stability in tomato leaves ≤72 h after dosing. This work identifies TaRy as a promising target for RNAi control of this widespread crop pest. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

CaCO3-complexed pH-responsive nanoparticles encapsulating mitoxantrone and celastrol enhance tumor chemoimmunotherapy

Modulating the immunosuppressive tumor microenvironment (TME) while enhancing antitumor immune responses is a promising strategy. In this study, we designed an acid-sensitive nanosystem (MCCaNPs) to demonstrate effective immunotherapy against cancer through the systemic delivery of immune-stimulating chemotherapy combinations. A pH-responsive nanoplatform containing CaCO3 was prepared by the double emulsion method, and mitoxantrone (MIT) and celastrol (CEL) were simultaneously encapsulated as immunogenic cell death (ICD) inducers. Due to the acid responsiveness of CaCO3, the nanoparticles rapidly consume H+ to relieve the acidic tumor microenvironment and explosively release CEL and MIT, showing inherent immunomodulatory activity in collaborative tumor chemoimmunotherapy. MIT and CEL synergistically trigger stronger ICD by inducing tumor cells to release calreticulin (CRT), high mobility group box 1 protein (HMGB1). Following the intravenous administration of MCCaNPs, the local tumor microenvironment(TME) was reprogrammed in mice-bearing tumors. This reprogramming was characterized by a significant increase in the density of tumor-infiltrating cytotoxic T lymphocytes(CTLs), ultimately prolonging survival. Therefore, this research proposes a promising approach to trigger immunogenic cell death collaboratively, aiming to boost the tumor CTLs infiltration for anticancer immunotherapy.

Extracellular vesicles powered cancer immunotherapy: Targeted delivery of adenovirus-based cancer vaccine in humanized melanoma model.

Malignant melanoma, a rapidly spreading form of skin cancer, is becoming more prevalent worldwide. While surgery is successful in treating early-stage melanoma, patients with advanced disease have only a 20% chance of surviving beyond five years. Melanomas with mutations in the NRAS gene are characterized for a more aggressive tumor biology, poorer prognosis and shorter survival. Hence, new therapeutic strategies are needed, especially for this specific group of patients. Novel approaches, such as cancer vaccines, offer promising solutions by stimulating the anti-tumor immune response. Nevertheless, their clinical efficacy is still modest and more effective approaches are required. Herein, we propose the systemic administration of the adenovirus-based cancer vaccine complexed in extracellular vesicles (EVs) with the aim of achieving a targeted therapeutic effect. The vaccine was based on previously tested oncolytic adenovirus Ad5/3-D24-ICOSL-CD40L in combination with melanoma-specific antigens targeting NRAS mutations to enhance the anticancer effect. The antineoplastic properties of the oncolytic vaccine were evaluated in xenograft MUG Mel-2 melanoma BALB/c nude mice. Moreover, to mimic the tumor microenvironment, while investigating at the same time immune cell infiltration and drug penetration, we established a 3D co-culture model based on human NRAS mutated MUG Mel-2 spheroids and PBMCs (HLA matched), which displayed a synergistic effect when treated with the cancer vaccine compared to relative controls. Subsequently, we investigated the systemic delivery of the vaccine in EV formulations in a humanized NSG MUG Mel-2 melanoma mouse model. Our study provides a promising strategy for a tumor-targeted vaccine delivery by EVs, resulting in improved anticancer efficacy and increased infiltration of tumor-infiltrating lymphocytes. This study explores the potential of EVs for the selective delivery of cancer vaccines against malignancies, such as NRAS melanoma. Overall, this research could pave the way for applying autologous EVs as a safe and efficacious tool for targeted cancer therapy.

Review on Oral Osmotic Tablet

Traditional oral medication delivery methods provide the drug with an immediate release and an efficient concentration at the intended location. Such a dosage regimen could lead to unexpected, ever-changing plasma concentrations. As a result, numerous regulated medication delivery systems are created. Among these, osmotic drug delivery systems (ODDS) and pulsatile drug delivery systems (PDDS) are becoming more and more significant because they improve patient treatment efficacy and compliance by delivering the medicine at precise times based on the course and physiological requirements of the disease. They regulate the drug’s delivery by using the osmotic pressure theory.To a significant extent, the drug’s release is unaffected by GIT physiological variables. Both targeted and systemic medication delivery are possible with these methods. The theoretical idea of drug delivery, various oral osmotic drug delivery system types, factors influencing the drug delivery system, benefits and drawbacks of these delivery systems, fundamental osmotic system components, evaluation parameters, difficulties, and emerging technologies in oral controlled drug delivery are all “highlighted” in this review.

Design and development of minoxidil-loaded nano carrier-based transdermal gel of trans-ethosomes for transdermal delivery system: Invitro evaluation studies

The present aim of the study was to develop a transdermal drug delivery system of the Nano-carrier-based Minoxidil-loaded transethosomal gel. In this study, we used Soyaphopshotidylcholine as a vesicle-forming agent and Sodium deoxycholate as a surfactant, and vesicle stabilizer as excipients. The Minoxidil transethosomes were prepared by thin film hydration technique. The prepared Minoxidil-loaded transethosomes (MTE) were evaluated and the particle size (189.83nm and 206.18nm), PDI(0.292 and 0.263), Zeta potential(-29.1mv and-28.2mv) and the entrapment efficiency (89.16±3.16 and 81.65±2.74) of MTE5 and MTE6. The MTE dispersion was further used to prepare gel, the gel base was prepared by using Carbopol, Xanthan gum, and HPMC K15. The optimized MTE-gel formulation was further evaluated, and the cumulative percentage of drug release was 98%, the 3 months stability studies show satisfactory results indicating good gel stability.

Medicated herbal chewing Gum to treat ulcers in mouth using Licorice and Capsicum annuum

This study explores the formulation and evaluation of herbal chewing gum containing extracts from Licorice (Glycyrrhiza glabra) and Capsicum Annuum, aimed at treating mouth ulcers. Licorice derived from roots. are known for their medicinal properties, it contains glycyrrhizin which is responsible for its sweet taste, including effects on sore throats, reduce inflammation and aid digestion. They contain various chemical compounds flavonoids such as such as liquirtin, rhamnoliquirilin, liquiritigenin, prenyllicoflavone A, glucoliquiritin apioside, metho-xyphaseolin, shinpterocarpin, shinflavanone, licopyranocoumarin, glisoflavone, licoarylcoumarin, coumarin-GU-12 and saponins namely glycyrrhizin flavonoids. While Capscicum annuum is recognized for its anti-oxidant, analgesic, insecticidal and anti ulcer properties, containing phytochemicals like carotenoids, flavonoids, capsaicinoids, phenolic compounds, vitamins and minerals. The preparation of the herbal chewing gum involved incorporating these extracts along with other necessary ingredients. Triethanolamine was added to adjust the pH to a suitable range (6.7-7.2) for oral mucosa compatibility. The study emphasizes that chewing gums serve as mobile drug delivery systems, allowing for the incorporation of herbal medicines for treating mouth ulcers. The convenience of chewing gum enables self-medication without the need for water, with active substances being released during chewing. This method facilitates local treatment of mouth diseases and systemic delivery through absorption via the buccal mucosa the herbal chewing gum represents an effective drug delivery system.

Nanoparticle-enhanced near-infrared fluorescence probes as a new frontier in cancer imaging

Recent advancements in nanotechnology have significantly enhanced the development of near-infrared fluorescence (NIRF) probes, positioning them as powerful tools in cancer imaging. This paper explores the unique advantages of nanoparticles incorporating NIR dyes, such as indocyanine green (ICG) and DiR, which exhibit deep tissue penetration and minimal background autofluorescence. The enhanced permeability and retention (EPR) effect facilitates selective accumulation in tumor tissues, enabling sophisticated imaging and precision-targeted drug delivery systems. This review highlights the remarkable potential of NIRF imaging techniques in molecular diagnostics, emphasizing their ability to differentiate malignant tissues at a molecular level. Additionally, we discuss various NIRF dye classifications, including cyanine and BODIPY-based probes, along with the development of multifunctional agents that enhance imaging specificity and therapeutic effectiveness. The integration of advanced targeting capabilities, including the use of antibodies and small molecules, further improves the precision of these imaging agents. While challenges remain regarding the pharmacokinetics and potential toxicity of nanoparticle-based probes, their capacity for real-time tumor tracking and the promise of multimodal imaging approaches underscore their transformative role in cancer diagnostics and treatment. By advancing the field of theranostics, nanoparticle-enhanced NIRF probes pave the way for personalized medicine and improved patient outcomes in oncology.

Leveraging Artificial Intelligence for Predictive Healthcare: A Data-Driven Approach to Early Diagnosis and Personalized Treatment

As noted, healthcare delivery systems are systems that always present organizational difficulties for any user and everyone related to these systems, but AI today is one of the widely-discussed and most frequently considered innovations that have prospects for radical improvement of the patient’s state and quality of life. AI solutions are on the verge of becoming integrated into clinical practice thanks to enhanced developments in the field, which means that there is a need to cover the part played by these technologies in healthcare and equip healthcare providers with the knowledge and resources needed to achieve that. This review article provides a broad, although dated, systematic synthesis of AI in clinical practice today, reviewing potential uses of AI in disease taxonomy and diagnosis, treatment suggestions, patient participation, and utilizing methodologies to consider the ethical and legal issues of AI and the persistent need for human insights and expertise. In order to establish the nature of the relationships and possible effects of AI in healthcare environments, the paper reviews the literature using PubMed/Medline, Scopus, and EMBASE databases. According to the findings, the application of AI technologies in health care delivery can greatly improve disease diagnosis, therapy choice, and clinical testing because, in contrast to human decision-making, AI algorithms analyze extensive data sets and outcompete human experts in specific tasks. It is accurate, cost-effective, time efficient, and free from human errors, advances the fields of pharmacogenomics and personalized medicine, optimizes the dosing of drugs, improves overall population health, establishes virtual healthcare services, and enhances mental health care, education, and trust between patients and physicians. Nevertheless, these and the following issues cannot be left unresolved: data privacy, AI bias, and the indispensability of the human factor.

A Journey Along the Boulevard of Bioactive Compounds from Natural Sources, with Cosmetic and Pharmaceutical Potential: Bee Venom, Cobra Venom, Ficus carica

Animal venom and plant extracts have been used since ancient times in traditional medicine worldwide. Natural components, valued for their safety and effectiveness, have been consistently used in cosmetic and pharmaceutical applications. We propose a journey along the boulevard of active compounds from natural sources, where bee venom (BV), cobra venom (CV), and Ficus carica reveal their individual therapeutic and cosmetic properties. The originality of this review lies in exploring the synergy of these bioactive sources, an approach that has not been presented in the literature. Although BV, CV, and Ficus carica have different origins and compositions, they have multiple common pharmacological and cosmetic actions, which make them ideal for inclusion in various products that can be used for skin care and health in general. Their anti-inflammatory, antioxidant, immunomodulatory, antimicrobial, neuroprotective, and regenerative properties give them an essential role in the creation of potential innovative and effective products in the pharmaceutical and cosmetics industry. Although many plant extracts have antioxidant and anti-inflammatory properties, Ficus carica was chosen due to its complex biochemical composition, which provides valuable benefits in skin regeneration and protection against oxidative stress. According to the International Nomenclature of Cosmetic Ingredients (INCI), Ficus carica is used in the form of an extract of fruits, leaves, juice, bark or stem, each having specific applicability in topical formulations; due to the diversity of bioactive compounds, it can amplify the effectiveness of BV and CV, helping to enhance their beneficial effects and reducing the risk of adverse effects, due to its well-tolerated nature. Thus, this combination of natural ingredients opens up new perspectives in the development of innovative products, optimizing efficiency and maintaining a favorable safety profile. In this context, due to the reported experimental results, the three natural sources caught our attention, and we conceived the present work, which is a review made following the analysis of the current progress in the study of the bioactive compounds present in BV, CV, and Ficus carica. We focused on the novelties regarding pharmacological and cosmetic actions presented in the literature, and we highlighted the safety profile, as well as the modern approaches regarding the delivery and transport systems of the active substances from the three natural sources, and we evaluated their prospects in therapeutic and cosmetic use. This paper not only expands our knowledge of bioactive compounds, but it can also generate new ideas and motivations for the research and development of innovative treatments and skincare methods.

Correction: Jin et al. A pH-Responsive DNA Tetrahedron/Methotrexate Drug Delivery System Used for Rheumatoid Arthritis Treatment. J. Funct. Biomater. 2023, 14, 541

In the original publication [...]

Development, characterization, and assessment of PLAROsomal vesicular system of curcumin for enhanced stability and therapeutic efficacy

Abstract Background Curcumin (CUR) is a natural polyphenol and one of the key phytoconstituents found in the rhizomes of Curcuma Longa. It exhibits various pharmacological properties, encompassing antioxidant, anticancer effects, antiseptic, and anti-inflammatory, among several others. A significant drawback of using CUR is its limited bioavailability, which primarily depends on gut microorganisms responsible for converting it into its bioavailable form. Therefore, the contemporary study intended to formulate a novel PLAROsomal vesicular delivery of CUR, i.e., CUR-PLAROsomes employing a design of experiments approach to examine the influence of various process parameters, such as particle size and drug percentage release. Result The prepared CUR-PLAROsomes were characterized for their physicochemical properties using various hyphenated tools. The CUR-PLAROsomes exhibited sizes ranging from 40 to 300 nm, and the optimized batch demonstrated a drug entrapment of 86.38 ± 0.22%. In-vitro anticancer studies were conducted using human colorectal adenocarcinoma cells (COLO320DM) and human breast adenocarcinoma (MCF-7). CUR-PLAROsomes exhibited significant in-vivo anti-inflammatory potential against carrageenan-induced paw edema. CUR-PLAROsomes were more potent against COLO320DM and MCF-7 cell lines, even at lower concentrations, than pure CUR. Conclusion Furthermore, based on the observations, it exhibits potential as an anti-inflammatory agent, suggesting that PLAROsomes are an effective vesicular drug delivery system. Highlights Newly introduced PLARosome is a next generation of Liposomes which have gain popularity owing to its better adaptability to overcome leakage problem of vesicular drug delivery system. This is the pioneer attempt to prepare Curcumin-loaded PLARosome as an anti-cancer and anti-inflammatory activity. Nano size of the PLAROsomes may contribute to enhance the efficacy of Curcumin as a target specific drug delivery system. Site specific delivery of phytoconstituents is possible by use of PLAROsomes as a novel drug delivery system. Graphical abstract

Physical, biochemical, and biological characterization of olive-derived lipid nanovesicles for drug delivery applications

AbstractExtracellular vesicles (EVs) have shown great promise as drug delivery system (DDS). However, their complex and costly production limit their development for clinical use. Interestingly, the plant kingdom can also produce EV-like nanovesicles that can easily be isolated and purified from a large quantity of raw material at a high yield. In this study, olive-derived nanovesicles (ODNVs) were isolated from raw fruits using serial centrifugations and their physical and biological features characterized to demonstrate their promising potential to be used as a DDS. Nanotracking particle analysis indicated an average size of 109.5 ± 3.0 nm and yield of 1012 ODNVs/mL for the purest fraction. Microscopy imaging, membrane fluidity assay and lipidomics analysis showed the presence of a rich lipid bilayer that significantly varied between different sources of ODNVs but showed a distinct signature compared to human EVs. Moreover, ODNVs were enriched in PEN1 and TET8 compared to raw fruits, suggesting an extracellular origin. Interestingly, ODNVs size and yield stayed unchanged after exposure to high temperature (70 °C for 1 h), wide pH range (5–10), and 50–100 nm extrusion, demonstrating high resistance to physical and chemical stresses. This high resistance allowed ODNVs to stay stable in water at 4 °C for a month, or with the addition of 25 mM trehalose for long-term freezing storage. Finally, ODNVs were internalized by both 2D and 3D cell culture without triggering significant cytotoxicity and immunogenicity. Importantly, the anticancer drug doxorubicin (dox) could be loaded by passive incubation within ODNVs and dox-loaded ODNVs decreased cell viability by 90% compared to only 70% for free dox at the same concentration, indicating a higher efficiency of drug delivery by ODNVs. In addition, this high cytotoxicity effect of dox-loaded ODNVs was shown to be stable after a 2-week storage at 4 °C. Together, these findings suggested that ODNVs represent a promising candidate as drug nanocarrier for various DDS clinical applications, as demonstrated by their biocompatibility, high resistance to stress, good stability in harsh environment, and improvement of anticancer drug efficacy.

Tripolar Bolalipids as Key Components of Sustained-Release Drug Delivery Systems

Tripolar Bolalipids as Key Components of Sustained-Release Drug Delivery Systems