Nanocarriers For Delivery Research Articles

Bioactive pH-sensitive nanoemulsion in melanoma cell lines

Melanoma is an aggressive form of skin cancer with elevated propensity to metastasize. One of the major critical issues in the treatment of oncological patients is represented by the development of toxicity and resistance to the available therapies. Great progress has been made in the field of nanotechnologies to limit the unwanted effects of anti-cancer treatments. We explored the potential of creating oil-in-water nanoemulsions composed of oleic acid, as a bioactive carrier for lipophilic drug delivery. This bioactive nanoemulsion was loaded with Curcumin, a natural fluorescent lipophilic compound, used as a model drug to evaluate nanoemulsion capability to: i) encapsulate the lipophilic moiety; ii) interact with the specific cells, and iii) improve the efficacy of the loaded model drug compared to the free one. Therefore, we evaluated the physical–chemical features of Curcumin-loaded nanoemulsions, confirming their pH sensibility and their stability over time. Moreover, the nanoemulsions were able to preserve the loaded Curcumin by degradation/destabilization phenomena. Finally, we verified some of the biological functions of Curcumin delivered by nanoemulsions in the B16F10 melanoma cell line. We obtained evidence of the biological action of Curcumin, suggesting oleic-based nanoemulsions as an efficient nanocarrier for lipophilic drug delivery.

Development of “Intelligent particles” for the treatment of dental caries

Dental caries is one of the most prevalent non-communicable diseases worldwide, mediated by a multispecies biofilm that consists of high levels of acidogenic bacteria which ferment sugar to acid and cause teeth demineralization. Current treatment practice remains insufficient in addressing 1) rapid clearance of therapeutic agents from the oral environment 2) destroying bacteria that contribute to the healthy oral microbiome. In addition, increasing concerns over antibiotic resistance calls for innovative alternatives. In this study, we developed a pH responsive nano-carrier for delivery of polycationic silver nanoparticles. Branched-PEI capped silver nanoparticles (BPEI-AgNPs) were encapsulated in a tannic acid − Fe (III) complex-modified poly(D,L-lactic-co-glycolic acid) (PLGA) particle (Fe(III)-TA/PLGA@BPEI-AgNPs) to enhance binding to the plaque biofilm and demonstrate “intelligence” by releasing BPEI-AgNPs under acidic conditions that promote dental caries The constructed Fe(III)-TA/PLGA@BPEI-AgNPs (intelligent particles − IPs) exhibited significant binding to an axenic S. mutans biofilm grown on hydroxyapatite. Ag+ ions were released faster from the IPs at pH 4.0 (cariogenic pH) compared to pH 7.4. The antibiofilm results indicated that IPs can significantly reduce S. mutans biofilm volume and viability under acidic conditions. Cytotoxicity on differentiated Caco-2 cells and human gingival fibroblasts indicated that IPs were not cytotoxic. These findings demonstrate great potential of IPs in the treatment of dental caries.

An Overview on the Physiopathology of the Blood-Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery.

The state of well-being and health of our body is regulated by the fine osmotic and biochemical balance established between the cells of the different tissues, organs, and systems. Specific districts of the human body are defined, kept in the correct state of functioning, and, therefore, protected from exogenous or endogenous insults of both mechanical, physical, and biological nature by the presence of different barrier systems. In addition to the placental barrier, which even acts as a linker between two different organisms, the mother and the fetus, all human body barriers, including the blood-brain barrier (BBB), blood-retinal barrier, blood-nerve barrier, blood-lymph barrier, and blood-cerebrospinal fluid barrier, operate to maintain the physiological homeostasis within tissues and organs. From a pharmaceutical point of view, the most challenging is undoubtedly the BBB, since its presence notably complicates the treatment of brain disorders. BBB action can impair the delivery of chemical drugs and biopharmaceuticals into the brain, reducing their therapeutic efficacy and/or increasing their unwanted bioaccumulation in the surrounding healthy tissues. Recent nanotechnological innovation provides advanced biomaterials and ad hoc customized engineering and functionalization methods able to assist in brain-targeted drug delivery. In this context, lipid nanocarriers, including both synthetic (liposomes, solid lipid nanoparticles, nanoemulsions, nanostructured lipid carriers, niosomes, proniosomes, and cubosomes) and cell-derived ones (extracellular vesicles and cell membrane-derived nanocarriers), are considered one of the most successful brain delivery systems due to their reasonable biocompatibility and ability to cross the BBB. This review aims to provide a complete and up-to-date point of view on the efficacy of the most varied lipid carriers, whether FDA-approved, involved in clinical trials, or used in in vitro or in vivo studies, for the treatment of inflammatory, cancerous, or infectious brain diseases.

A pH transformable nanocarrier for gradual and precise delivery of a natural immunomodulator and chemotherapy agent to trigger tumor apoptosis

Chemotherapy coupled with immunotherapy exerts strong antitumor effects. Research efforts have been directed to investigate the simultaneous delivery of immunomodulators and chemotherapeutic agents into immune or tumor cells. However, the optimal combination effects are undermined. In this study, we constructed a pH-hypersensitive multifunctional nano-platform (Dual NP) combining the procedural release and precise delivery of the natural immunomodulator, chlorogenic acid (CHA), and the chemotherapeutic agent, paclitaxel (PTX), to M2-TAMs and tumor cells, respectively. This combination is designed to increase the antitumor efficacy of PTX and increase the immunomodulatory effect of CHA to generate a potent immune response. We also assessed the in vitro and in vivo characteristics of Dual NP in repairing the immunosuppressive tumor microenvironment (TME) and exerting antitumor effects. Our findings indicated that targeted delivery and reversal of M2-TAMs by CHA can achieve a positive feedback loop on remodeling the immunosuppressive TME, such as increasing the infiltration of T cells and DCs, decreasing the proportion of MDSCs, elevating the levels of pro-inflammatory cytokines (IFN-γ, IL-2, and IL-12), and decreasing the levels of anti-inflammatory cytokines (IL-10 and TGF-β1). These findings show that intravenously administered Dual NP can be a potential treatment strategy for chemo-immunotherapy.

Harnessing exosomes and plant-derived exosomes as nanocarriers for the efficient delivery of plant bioactives.

Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150nm, produced by various organisms through the endosomal pathway. Recent studies have established the utilization of exosomes as nanocarriers for drug distribution across various therapeutic areas including cancer, acute liver injury, neuroprotection, oxidative stress, inflammation, etc. The importance of plant-derived exosomes and exosome vesicles derived from mammalian cells or milk, loaded with potent plant bioactives for various therapeutic indications are discussed along with insights into future perspectives. Moreover, this review provides a detailed understanding of exosome biogenesis, their composition, classification, stability of different types of exosomes, and different routes of administration along with the standard techniques used for isolating, purifying, and characterizing exosomes.

Recent advancements in lipid nanoparticle technology for oral insulin delivery

Nanotechnology is important in many industries, particularly in drug delivery and administration. This technology has been used to create nanocarriers for enteral drug delivery. There are different types of nanocarriers including polysaccharide-based and lipid-based nanocarriers. Lipid nanoparticles have recently been developed for loading and administering insulin via the enteral route to treat diabetes mellitus. Insulin cannot be administered orally due to its low bioavailability, extreme gastrointestinal conditions, and instability. When insulin is loaded onto these nanocarriers, it increases bioavailability, stability, drug release pattern control, and protects insulin from extreme conditions. This review article aims to discuss recent applications as well as novel methods and approaches for oral insulin delivery using liposomes, solid lipid nanoparticles, and nanostructured lipid carriers.

Retraction Note: ZnO as a promising nanocarrier for efficient delivery of 5-fluorouracil anticancer drug

Retraction Note: ZnO as a promising nanocarrier for efficient delivery of 5-fluorouracil anticancer drug

Investigation Cytotoxicity and Curcumin Release Behavior by Pyranopyrazole-TiO2@niosome Carrier for Breast Cancer Treatment.

In the present study, we present a pyranopyrazole-TiO2 which is encapsulated with a niosome as nanocarrier for delivery of curcumin into breast cancer cells. Nanocarrier porous TiO2 is biocompatible and with a high specific surface area and a large pore volume and was used to carry pyranopyrazole, which has been reported as an anti-cancer. Niosome in the outer layer, helpful for loading curcumin into the niosomal layer, demonstrates a pH-dependent release and can be effective for cancer treatment. Entrapment efficiency of curcumin was found at 81.02% in carriers. The results of MTT and flow cytometry revealed that apoptosis is notably enhanced by loading curcumin on pyranopyrazole-TiO2@niosome. Also, there was high biocompatibility with MCF-10A, while exhibiting significant anti-cancer and anti-metastatic effects on MCF-7, whose cell viability was 38.79% in the loaded curcumin on carrier and was more than other samples even, than free curcumin (42.82%). Furthermore, the regulation of gene expression in cancer cells decreased the regulation of MMP-2 and MMP-9 genes and increased the expression of caspase-3 and caspase-9 genes. Finally, fluorescence activity in MCF-7 significantly increased after treatment with samples.

Folic acid-modified nanocrystalline cellulose for enhanced delivery and anti-cancer effects of crocin

Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and stability, which can be overcome through nanocarrier delivery systems. This study used surface-modified Nano-crystalline cellulose (NCC) to deliver crocin to cancer cells. NCC modified with CTAB were loaded with crocin and then conjugated with folic acid (NCF-CR-NPs). The synthesized nanoparticles (NPs) were characterized using FTIR, XRD, DLS, and FESEM. The crystallinity index of NCC was 66.64%, higher than microcrystalline cellulose (61.4%). The crocin loading and encapsulation efficiency in NCF-CR-NPs were evaluated. Toxicity testing by MTT assay showed that NCF-CR-NPs had higher toxicity against various cancer cell lines, including colon cancer HT-29 cells (IC50 ~ 11.6 μg/ml), compared to free crocin. Fluorescent staining, flow cytometry, and molecular analysis confirmed that NCF-CR-NPs induced apoptosis in HT-29 cells by increasing p53 and caspase 8 expression. The antioxidant capacity of NCF-CR-NPs was also evaluated using ABTS and DPPH radical scavenging assays. NCF-CR-NPs exhibited high free radical scavenging ability, with an IC50 of ~ 46.5 μg/ml for ABTS. In conclusion, this study demonstrates the potential of NCF-CR-NPs to deliver crocin to cancer cells effectively. The NPs exhibited enhanced anti-cancer and antioxidant activities compared to free crocin, making them a promising nanocarrier system for crocin-based cancer therapy.

Therapeutic expression of RAS Degrader RRSP in Pancreatic Cancer via Nanocarrier-mediated mRNA delivery.

About one-third of all human cancers encode abnormal RAS proteins locked in a constitutively activated state to drive malignant transformation and uncontrolled tumor growth. Despite progress in development of small molecules for treatment of mutant KRAS cancers, there is a need for a pan-RAS inhibitor that is effective against all RAS isoforms and variants and that avoids drug resistance. We have previously shown that the naturally occurring bacterial enzyme RAS/RAP1-specific endopeptidase (RRSP) is a potent RAS degrader that can be re-engineered as a biologic therapy to induce regression of colorectal, breast, and pancreatic tumors. Here, we have developed a strategy for in vivo expression of this RAS degrader via mRNA delivery using a synthetic nonviral gene delivery platform composed of the poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) block copolymer conjugated to a dendritic cationic peptide (PPDP2). Using this strategy, PPDP2 is shown to deliver mRNA to both human and mouse pancreatic cells resulting in RRSP gene expression, activity, and loss of cell proliferation. Further, pancreatic tumors are reduced with residual tumors lacking detectable RAS and phosphorylated ERK. These data support that mRNA-loaded synthetic nanocarrier delivery of a RAS degrader can interrupt the RAS signaling system within pancreatic cancer cells while avoiding side effects during therapy.

Biocompatible Chitosan/Starch/Graphene Quantum Dots/Titanium Dioxide Nanocomposite: A Stimuli-Responsive, Porous Nanocarrier for Prolonged Quercetin Delivery in Lung Cancer Treatment

Biocompatible Chitosan/Starch/Graphene Quantum Dots/Titanium Dioxide Nanocomposite: A Stimuli-Responsive, Porous Nanocarrier for Prolonged Quercetin Delivery in Lung Cancer Treatment

Covalent Organic Frameworks as Potential Drug Carriers and Chemotherapeutic Agents for Ovarian Cancers.

Anticancer drugs are often associated with limitations such as poor stability in aqueous solutions, limited cell membrane permeability, nonspecific targeting, and irregular drug release when taken orally. One possible solution to these problems is the use of nanocarriers of drug molecules, particularly those with targeting ability, stimuli-responsive properties, and high drug loading capacity. These nanocarriers can improve drug stability, increase cellular uptake, allow specific targeting of cancer cells, and provide controlled drug release. While improving the therapeutic efficacy of cancer drugs, contemporary researchers also aim to reduce their associated side effects, such that cancer patients are offered with a more effective and targeted treatment strategy. Herein, a set of nine porous covalent organic frameworks (COFs) were tested as drug delivery nanocarriers. Among these, paclitaxel loaded in COF-3 was most effective against the proliferation of ovarian cancer cells. This study highlights the emerging potential of COFs in the field of therapeutic drug delivery. Due to their biocompatibility, these porous COFs provide a viable substrate for controlled drug release, making them attractive candidates for improving drug delivery systems. This work also demonstrates the potential of COFs as efficient drug delivery agents, thereby opening up new opportunities in the field of sarcoma therapy.

Au-doped Fe3O4 nanoparticle as an effective nanocarrier for delivery of 5-fluorouracil anti-liver cancer drug

5-Fluorouracil (5-FU) is an important chemotherapy that is classified as an antimetabolite and is widely used in cancer treatment, particularly for liver cancer. Yet, administering high doses of 5-FU for liver cancer can result in a range of adverse effects. Therefore, employing a suitable delivery system for this important drug can greatly enhance its safety and effectiveness, leading to improved treatment outcomes and better quality of life for patients. Au-doped Fe3O4 nanoparticles have attracted significant interest in scientific research due to their unique physical and chemical properties. This study presents a straightforward and cost-effective method for synthesizing Au-doped Fe3O4 nanoparticles by using a natural reducing agent. The study involved a comprehensive analysis of the Au-doped Fe3O4 nanoparticles using various techniques such as FT-IR, XRD, XPS, FE-SEM, TEM, UV–Vis, EDS, VSM, and DLS. The delivery experiments indicated a loading capacity of approximately 78 %. The release profile showed slow release profile, dependent on pH. Therefore, 41 % release was detected under physiological pH 7.4, while a much faster release was observed at pH 5.7 (84 %) within 48 h. Moreover, the high crystallinity degree of approximately 84 % was attained for Au-doped Fe3O4, confirming this nanoparticle as an efficient drug delivery system. In another attempt, PDI and hydrated particle size distribution analyses on Au-doped Fe3O4 showed no significant change in size after 72 h. Therefore, it can be concluded that drug loaded Au-doped Fe3O4 is stable enough and maintained its efficacy after a long time of 3 days. Finally, an in vitro assessment of cellular cytotoxicity was performed on a liver cancer cell line (HepG2) to assess the safety and efficacy of the Au-doped Fe3O4 nanoparticles. The results from the MTT assay confirmed the potential of these nanoparticles as a promising vehicle for delivering 5-Fluorouracil.

Graphene Oxide Nanocarriers for Effective Drug Delivery in Breast Cancer Treatment

Breast cancer is the most commonly diagnosed form of cancer globally, with women having a higher risk of developing the disease. Current treatment approaches, such as surgery, chemotherapy, and radiotherapy, encounter significant difficulties due to the heterogeneous and intricate regulation of tumors. Nanotechnology, especially the utilization of graphene oxide (GO), presents a promising approach to overcoming the limitations of traditional treatments. GO's unique properties, including its two-dimensional structure, functional groups, and high surface area, make it an ideal material for developing multifunctional nanocarriers. Graphene oxide-based nanocarriers have demonstrated immense potential in breast cancer therapeutics by overcoming the limitations and adverse reactions associated with chemotherapy. The functionalization of GO's surface using biocompatible substances like chitosan and polyethylene glycol improves the cytotoxicity of GO. Enhancing the cytotoxicity also improves the ability to treat tumors that have developed resistance to traditional treatments. These findings demonstrate the promising efficacy of GO-based nanocarriers in treating breast cancer and pave the way for the development of more precise and efficient treatment strategies in the future, potentially improving therapeutic outcomes.

Liposome nanoparticle conjugation and cell penetrating peptide sequences (CPPs) enhance the cellular delivery of the tau aggregation inhibitor RI-AG03.

Given the pathological role of Tau aggregation in Alzheimer's disease (AD), our laboratory previously developed the novel Tau aggregation inhibitor peptide, RI-AG03. As Tau aggregates accumulate intracellularly, it is essential that the peptide can traverse the cell membrane. Here we examine the cellular uptake and intracellular trafficking of RI-AG03, in both a free and liposome-conjugated form. We also characterize the impact of adding the cell-penetrating peptide (CPP) sequences, polyarginine (polyR) or transactivator of transcription (TAT), to RI-AG03. Our data show that liposome conjugation of CPP containing RI-AG03 peptides, with either the polyR or TAT sequence, increased cellular liposome association three-fold. Inhibition of macropinocytosis modestly reduced the uptake of unconjugated and RI-AG03-polyR-linked liposomes, while having no effect on RI-AG03-TAT-conjugated liposome uptake. Further supporting macropinocytosis-mediated internalization, a 'fair' co-localisation of the free and liposome-conjugated RI-AG03-polyR peptide with macropinosomes and lysosomes was observed. Interestingly, we also demonstrate that RI-AG03-polyR detaches from liposomes following cellular uptake, thereby largely evading organellar entrapment. Collectively, our data indicate that direct membrane penetration and macropinocytosis are key routes for the internalization of liposomes conjugated with CPP containing RI-AG03. Our study also demonstrates that peptide-liposomes are suitable nanocarriers for the cellular delivery of RI-AG03, furthering their potential use in targeting Tau pathology in AD.

Attenuating intervertebral disc degeneration through spermidine-delivery nanoplatform based on polydopamine for persistent regulation of oxidative stress

As one of the most widespread musculoskeletal diseases worldwide, intervertebral disc degeneration (IVDD) remains an intractable clinical problem. Currently, oxidative stress has been widely considered as a significant risk factor in the IVDD pathological changes, and targeting oxidative stress injury to improve the harsh microenvironment may provide a novel and promising strategy for disc repair. It is evident that spermidine (SPD) has the ability to attenuate oxidative stress across several disease models. However, limited research exists regarding its impact on oxidative stress within the intervertebral disc. Moreover, enhancing the local utilization rate of SPD holds great significance in IVDD management. This study aimed to develop an intelligent biodegradable mesoporous polydopamine (PDA) nanoplatform for sustained release of SPD. The obtained PDA nanoparticles with spherical morphology and mesoporous structure released loaded-therapeutic molecules under low pH and H2O2. Combined treatment with SPD loaded into PDA nanoparticles (SPD/PDA) resulted in better therapeutic potential than those with SPD alone on oxidative stress injury. Furthermore, both SPD and SPD/PDA could induce anti-inflammatory M2 macrophage polarization. Upon injection into degenerative IVDs, the SPD/PDA group achieved a good repair efficacy with a long-term therapeutic effect. These findings indicated that the synergized use of SPD with responsive drug delivery nanocarriers may steadily scavenge reactive oxygen species and provide an effective approach toward the treatment of IVDD.

Review of Oral Tablet

Abstract: Oral drug delivery is noninvasive, has a high rate of patient compliance, is easy to handle, and doesn't require any special sterile settings, it is the most popular method of administration. Nevertheless, a number of physical, biological, and pharmacological obstacles that certain medications must overcome in order to be absorbed into the systemic circulation reduce their therapeutic efficiency. The use of nanocarriers to deliver drugs orally has proven to be an effective solution to the aforementioned problems and is being explored as a potential replacement for oral medication administration. This chapter provides an overview of the latest developments in the use of nanocarriers for oral medication delivery in the treatment of different disorders. The chapter also describes how diverse nanocarrier designs and technologies improve therapeutic potential by overcoming physical, biological, and biochemical obstacles. it is easy to produce, has few sterility limitations, is less expensive, has flexible dosage form design, and has high patient compliance, oral drug delivery (ODD) is the most convenient and favored method of drug administration. However, low medication bioavailability—which is influenced by three crucial factors—is one of the difficulties associated with oral drug delivery. The other is solubility. Many mathematical models that predict the medication's rate of solubility and dissolution have been developed in order to achieve efficient drug absorption in vivo. Similarly, models that are noncellular and cellular determine permeability. Furthermore, the medication's behavior in the gastrointestinal tract (GIT) is influenced by physiological parameters, such as pH, microbial colonization, and enzymes, as well as intrinsic drug properties. A drug's dosage form is a method of getting it into a living organism. The medicine must be administered to the site of action at a rate and concentration that will maximize therapeutic benefit and minimize side effects in order to provide the intended result. Although the oral method is still commonly used, swallowing tablets and capsules can be a regular problem. As a result, numerous studies on cutting-edge drug delivery methods have been conducted. This review focuses on oral dispersible tablets, a novel approach to drug delivery systems that are currently more focused on formulation and set a new course that not only helped patients increase their level of therapy compliance.

Electrochemical Characterization of the Encapsulation and Release of 5-Fluorouracil in Nanocarriers Formed from Soy Lecithin Vesicles.

5-Fluorouracil (5-FU) is an antineoplastic agent known for its low bioavailability and limited cellular penetration, often resulting in adverse effects on healthy cells. Thus, finding vehicles that enhance bioavailability, enable controlled release, and mitigate adverse effects is crucial. The study focuses on encapsulating 5-FU within soy lecithin vesicles (SLVs) and assessing its impact on the carrier's properties and functionality. Results show that incorporating 5-FU does not affect SLVs' size or polydispersity, even postlyophilization. Liberation of 5-FU from SLVs requires system disruption rather than spontaneous release, with an encapsulation efficiency of approximately 43% determined using Square Wave Voltammetry. Cytotoxicity assays on colorectal cancer cells reveal SLV-based delivery's significant efficacy, surpassing free drug solution effects with 45% cell viability after 72 h vs 73% viability. The research addresses 5-FU's limited bioavailability by creating a biocompatible nanocarrier for efficient drug delivery, highlighting SLVs as promising for targeted cancer therapy due to sustained antiproliferative effects and improved cellular uptake. The study underscores the importance of tailored drug delivery systems in enhancing therapeutic outcomes and suggests SLV/5-FU formulations as a potential advancement in cancer treatment strategies.

Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy.

The exogenous delivery of miRNA to mimic and restore miRNA-34a activity in various cancer models holds significant promise in cancer treatment. Nevertheless, its effectiveness is often impeded by challenges, including a short half-life, propensity for off-target accumulation, susceptibility to inactivation by blood-based enzymes, concerns regarding patient safety, and the substantial cost associated with scaling up. As a means of overcoming these barriers, we propose the development of miRNA-loaded Tat-A86 nanoparticles by virtue of Tat-A86's ability to shield the loaded agent from external environmental factors, reducing degradation and inactivation, while enhancing circulation time and targeted accumulation. Genetically engineered Tat-A86, featuring 16 copies of the interleukin-4 receptor (IL-4R)-binding peptide (AP1), Tat for tumor penetration, and an elastin-like polypeptide (ELP) for presenting target ligands and ensuring stability, served as the basis for this delivery system. Comparative groups, including Tat-E60 and A86, were employed to discern differences in binding and penetration. The designed ELP-based nanoparticle Tat-A86 effectively condensed miRNA, forming stable nanocomplexes under physiological conditions. The miRNA/Tat-A86 formulation bound specifically to tumor cells and facilitated stable miRNA delivery into them, effectively inhibiting tumor growth. The efficacy of miRNA/Tat-A86 was further evaluated using three-dimensional spheroids of lewis lung carcinoma (LLC) as in vitro model and LLC tumor-bearing mice as an in vivo model. It was found that miRNA/Tat-A86 facilitates effective cell killing by markedly improving miRNA penetration, leading to a substantial reduction in the size of LLC spheroids. Compared to other controls, Tat-A86 demonstrated superior efficacy in suppressing the growth of 3D cellular aggregates. Moreover, at equivalent doses, miRNA-34a delivered by Tat-A86 inhibited the growth of LLC cells in allograft mice. Overall, these studies demonstrate that Tat-A86 nanoparticles can deliver miRNA systemically, overcoming the basic hurdles impeding miRNA delivery by facilitating both miRNA uptake and stability, ultimately leading to improved therapeutic effects.

A journey through the history of PEGylated drug delivery nanocarriers

This note aims to inspire through providing a personal view of the development and potential Drug Delivery Nanocarriers functionalized with polythyleneglycol (PEG). This polymer has been used extensively in Pharmaceutical Technology in a variety of compositions, including polyethylene oxide (PEO)-based surfactants. However, the concept of PEGylation, which started in the 70’s, differs from the functionality of a surfactant, already discloses in the 50’s. Here, we strictly adhere to the biological functionality of PEGylated nanocarriers intended to have a reduced interaction with proteins and, therefore, modify their biodistribution as well as facilitate their diffusion across mucus and other biological barriers. We analyze how this concept has evolved over the years and the benefit obtained so far in terms of marketed nanomedicines and provide the readers with a prospect view of the topic.