Nanocarriers For Drug Delivery Research Articles

Lipid-based Nanocarrier Drug Delivery Approach for Biomedical Application

Abstract: The development of nanosized drug-carrier systems has been investigated over the past few decades using various techniques. The two main categories of these systems are polymeric nanoparticles and lipid nanoparticles (LNPs). The toxicological risk associated with lipid nanoparticles is significantly lower than the danger associated with polymeric nanoparticles due to the materials' natural and biological origins. Lipid-based drug delivery systems like Nanostructured lipid carriers (NLCs) and Solid Lipid Nanoparticles (SLNs) are well-established nanotechnology systems for preparing all major pharmaceuticals. These delivery systems can be scaled up with easy manufacturing procedures and are biocompatible. NLCs are the second generation of lipid-based nanocarriers (SLNs), formed by combining solid and liquid biocompatible lipids to form an unstructured matrix that provides high entrapment efficiency of active constituents. LNPs can promote the distribution of active pharmaceutical ingredients to the target site. Increasing the active drug concentration to target organ LNPs enhances the therapeutic effectiveness and reduces the side effects. This paper reviews the structure of SLNs and different NLCs, various steps involved in manufacturing lipid nanoparticles, excipients used in the formulation, and applications for targeted drug delivery.

Applications of nanotechnology-mediated herbal nanosystems for ophthalmic drug.

In recent years, herbal nanomedicines have gained tremendous popularity for novel drug discovery. Nanotechnology has provided several advances in the healthcare sector, emerging several novel nanocarriers that potentiate the bioavailability and therapeutic efficacy of the herbal drug. The recent advances in nanotechnology with accelerated strategies of ophthalmic nanosystems have paved a new path for overcoming the limitations associated with ocular drug delivery systems, such as low bioavailability, poor absorption, stability, and precorneal drug loss. Ophthalmic drug delivery is challenging due to anatomical and physiological barriers. Due to the presence of these barriers, the herbal drug entry into the eyes can be affected when administered by following multiple routes, i.e., topical, injectables, or systemic. However, the advancement of nanotechnology with intelligent systems enables the herbal active constituent to successfully entrap within the system, which is usually difficult to reach employing conventional herbal formulations. Herbal-loaded nanocarrier drug delivery systems demonstrated enhanced herbal drug permeation and prolonged herbal drug delivery. In this current manuscript, an extensive search is conducted for original research papers using databases Viz., PubMed, Google Scholar, Science Direct, Web of Science, etc. Further painstaking efforts are made to compile and update the novel herbal nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructure lipid carriers, micelles, niosomes, nanoemulsions, dendrimers, etc., which are mostly used for ophthalmic drug delivery system. This article presents a comprehensive survey of diverse applications used for the preventative measures and treatment therapy of varied eye disorders. Further, this article highlights the recent findings that the innovators are exclusively working on ophthalmic nanosystems for herbal drug delivery systems. The nanocarriers are promising drug delivery systems that enable an effective and supreme therapeutic potential circumventing the limitations associated with conventional ocular drug delivery systems. The nanotechnology-based approach is useful to encapsulate the herbal bioactive and prevent them from degradation and therefore providing them for controlled and sustained release with enhanced herbal drug permeation. Extensive research is still being carried out in the field of herbal nanotechnology to design an ophthalmic nanosystem with improved.

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.

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.

Theoretical investigations on modeling blood flow through vessel for understanding effectiveness of magnetic nanocarrier drug delivery systems

Theoretical investigations on modeling blood flow through vessel for understanding effectiveness of magnetic nanocarrier drug delivery systems

Fluorescent Chiral Quantum Dots to Unveil Origin-Dependent Exosome Uptake and Cargo Release.

Exosomes are promising nanocarriers for drug delivery. Yet, it is challenging to apply exosomes in clinical use due to the limited understanding of their physiological functions. While cellular uptake of exosomes is generally known through endocytosis and/or membrane fusion, the mechanisms of origin-dependent cellular uptake and subsequent cargo release of exosomes into recipient cells are still unclear. Herein, we investigated the intricate mechanisms of exosome entry into recipient cells and intracellular cargo release. In this study, we utilized chiral graphene quantum dots (GQDs) as representatives of exosomal cargo, taking advantage of the superior permeability of chiral GQDs into lipid membranes as well as their excellent optical properties for tracking analysis. We observed that the preferential cellular uptake of exosomes derived from the same cell-of-origin (intraspecies exosomes) is higher than that of exosomes derived from different cell-of-origin (cross-species exosomes). This uptake enhancement was attributed to receptor-ligand interaction-mediated endocytosis, as we identified the expression of specific ligands on exosomes that favorably interact with their parental cells and confirmed the higher lysosomal entrapment of intraspecies exosomes (intraspecies endocytic uptake). On the other hand, we found that the uptake of cross-species exosomes primarily occurred through membrane fusion, followed by direct cargo release into the cytosol (cross-species direct fusion uptake). We revealed the underlying mechanisms involved in the cellular uptake and subsequent cargo release of exosomes depending on their cell-of-origin and recipient cell types. Overall, this study envisions valuable insights into further advancements in effective drug delivery using exosomes, as well as a comprehensive understanding of cellular communication, including disease pathogenesis.

Fabrication of Rhenium Disulfide/Mesoporous Silica Core-Shell Nanoparticles for a pH-Responsive Drug Release and Combined Chemo-Photothermal Therapy.

A stimuli-responsive drug delivery nanocarrier with a core-shell structure combining photothermal therapy and chemotherapy for killing cancer cells was constructed in this study. The multifunctional nanocarrier ReS2@mSiO2-RhB entails an ReS2 hierarchical nanosphere coated with a fluorescent mesoporous silica shell. The three-dimensional hierarchical ReS2 nanostructure is capable of effectively absorbing near-infrared (NIR) light and converting it into heat. These ReS2 nanospheres were generated by a hydrothermal synthesis process leading to the self-assembly of few-layered ReS2 nanosheets. The mesoporous silica shell was further coated on the surface of the ReS2 nanospheres through a surfactant-templating sol-gel approach to provide accessible mesopores for drug uploading. A fluorescent dye (Rhodamine B) was covalently attached to silica precursors and incorporated during synthesis in the mesoporous silica walls toward conferring imaging capability to the nanocarrier. Doxorubicin (DOX), a known cancer drug, was used in a proof-of-concept study to assess the material's ability to function as a drug delivery carrier. While the silica pores are not capped, the drug molecule loading and release take advantage of the pH-governed electrostatic interactions between the drug and silica wall. The ReS2@mSiO2-RhB enabled a drug loading content as high as 19.83 mg/g doxorubicin. The ReS2@mSiO2-RhB-DOX nanocarrier's cumulative drug release rate at pH values that simulate physiological conditions showed significant pH responsiveness, reaching 59.8% at pH 6.8 and 98.5% and pH 5.5. The in vitro testing using HeLa cervical cancer cells proved that ReS2@mSiO2-RhB-DOX has a strong cancer eradication ability upon irradiation with an NIR laser owing to the combined drug delivery and photothermal effect. The results highlight the potential of ReS2@mSiO2-RhB nanoparticles for combined cancer therapy in the future.

Functionalized graphene oxide NPs as a nanocarrier for drug delivery system in quercetin/ lurbinectedin as dual sensitive therapeutics for A549 lung cancer treatment

Functionalized graphene oxide nanoparticles (NPs) have emerged as promising nanocarriers for drug delivery in lung cancer therapy. Quercetin and lurbinectedin encapsulated in graphene oxide (GO) NPs are tested for treating A549 lung cancer cells. Spectroscopic analyses show that graphene oxide functionalization creates a transparent, smooth surface for drug loading. Treatment with quercetin/lurbinectedin-loaded GO NPs induces notable cytotoxic effects in lung cancer cells, as evidenced by distinct morphological alterations and confirmed apoptotic cellular death observed through fluorescence microscopy. Additionally, our study highlights the impact of this approach on lung cancer metastasis, supported by qRT-PCR analysis of relative gene expression levels, including p53, Bax, Caspase-3, and Bcl 2, revealing robust molecular mechanisms underlying therapeutic efficacy against A549 and PC9 cell lines. Flow cytometric analyses further confirm the induction of cellular death in lung cancer cells following administration of the nanoformulation. Our findings show that quercetin/lurbinectedin-loaded GO NPs may be a promising lung cancer treatment, opening new avenues for targeted and effective therapies.

An updated review on liposomes

Liposomes, tiny bubbles made from the same material as a cell membrane, are considered the most successful nanocarriers for drug delivery. They are biocompatible and stable, encapsulating both hydrophilic and lipophilic drugs and protecting them from degradation. Liposomes are the most commonly used drug delivery vehicles due to their high drug trapping capacity and efficiency. These offer controlled release, targeted drug delivery, increased therapeutic efficacy, and reduced dosing frequency. Liposome-based drug formulations have been approved for clinical use and are the subject of extensive research. Recent liposomal formulations aim to reduce toxicity and increase target site accumulation. With numerous advantages, liposomes prove their uniqueness in safe drug delivery in various areas of pharmacy and medicine. We will keep an eye on overall updated review on liposomes classification, their structural components, mechanism of action, stability, method of preparation, their evaluation tests and applications.

Application of electron paramagnetic resonance spectroscopy for determining the relative nanoenvironment fluidity of polymeric micelles.

Polymeric micelles are nanocarriers for drug, protein and gene delivery due to their unique core/shell structure, which encapsulates and protects therapeutic cargos with diverse physicochemical properties. However, information regarding the micellar nanoenvironment's fluidity can provide unique insight into their makeup. In this study, we used electron paramagnetic resonance (EPR) spectroscopy to study free radical spin probe (5-doxylstearate methyl ester, 5-MDS, and 16-doxylstearic acid, 16-DS) behaviour in methoxy-poly(ethylene oxide)-poly(α-benzyl carboxylate-ε-caprolactone) (PEO-PBCL) and methoxy-poly(ethylene oxide)-poly(ε-caprolactone) (PEO-PCL) polymeric micelles. Spin probes provided information about the spectroscopic rotational correlation time (τ, s) and the spectroscopic partition parameter F. We hypothesized that spin probes would partition into the polymeric micelles, and these parameters would be calculated. The results showed that both 5-MDS and 16-DS spectra were modulated in the presence of polymeric micelles. Based on τ values, 5-MDS revealed that PEO-PCL (τ = 3.92 ± 0.26 × 10-8s) was more fluid than PEO-PBCL (τ = 7.15 ± 0.63 × 10-8s). The F parameter, however, could not be calculated due to the rotational hindrance of the probe within the micelles. With 16-DS, more probe rotation was observed, and although the F parameter could be calculated, it was not helpful to distinguish the micelles' fluidity. Also, doxorubicin-loading interfered with the spin probes, particularly for 16-DS. However, using simulations, we could distinguish the hydrophilic and hydrophobic components of the 16-DS probe. The findings suggest that EPR spectroscopy is a valuable method for determining core fluidity in polymeric micelles.

Engineered protein cages with enhanced extracellular drug release for elevated antitumor efficacy

Human heavy chain ferritin (HFn) protein cage has been explored as a nanocarrier for targeted anticancer drug delivery. Here, we introduced a matrix metalloproteinases (MMPs)-cleavable sequence into the DE loop of HFn, creating an MMP-responsive variant, MR-HFn, for localized and extracellular drug release. The crystal structure of MR-HFn revealed that the addition of the MMPs recognition sequence did not affect the self-assembly of HFn but presented a surface-exposed loop susceptible to MMPs cleavage. Biochemical analysis indicated that this engineered protein cage is responsive to MMPs, enabling the targeted release of encapsulated drugs. To evaluate the therapeutic potential of this engineered protein cage, monosubstituted β-carboxy phthalocyanine zinc (CPZ), a type of photosensitizer, was loaded inside this protein cage. The prepared CPZ@MR-HFn showed higher uptake and stronger phototoxicity in MMPs overexpressed tumor cells, as well as enhanced penetration into multicellular tumor spheroids compared with its counterpart CPZ@HFn in vitro. In vivo, CPZ@MR-HFn displayed a higher tumor inhibitory rate than CPZ@HFn under illumination. These results indicated that MR-HFn is a promising nanocarrier for anticancer drug delivery and the MMP-responsive strategy here can also be adapted for other stimuli.

Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

Folate-mediated Transport of Nanoparticles across the Placenta.

In this study, a prototype of a targeted nanocarrier for drug delivery for prenatal therapy of the developing fetus was developed and examined in vitro and ex vivo. The folate transport mechanism in the human placenta was utilized as a possible pathway for the transplacental delivery of targeted nanoparticles. Several types of folic acid-decorated polymeric nanoparticles were synthesized and characterized. During transport studies of targeted and non-targeted fluorescent nanoparticles across the placental barrier, the apparent permeability values, uptake, transfer indices, and distribution in placental tissue were determined. The nanoparticles had no effect on BeWo b30 cell viability. In vitro, studies showed significantly higher apparent permeability of the targeted nanoparticles across the cell monolayers as compared to the nontargeted nanoparticles (Pe = 5.92 ± 1.44 ×10-6 cm/s for PLGA-PEG-FA vs. 1.26 ± 0.31 ×10-6 cm/s for PLGA-PEG, P < 0.05), and the transport of the targeted nanoparticles was significantly inhibited by excess folate. Ex vivo placental perfusion showed significantly greater accumulation of the targeted nanoparticles in the placental tissue (4.31 ± 0.91%/g for PLGA-PEG-FA vs. 2.07 ± 0.26%/g for PLGA-PEG). The data obtained suggested different mechanisms for the uptake and transplacental transfer of targeted versus nontargeted nanoparticles. This targeted nanoformulation may be a promising strategy for fetal drug therapy.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.

Molecular Bottlebrushes as Emerging Nanocarriers: Material Design and Biomedical Application.

As a unique unimolecular nanoobject, molecular bottlebrushes (MBBs) have attracted great interest from researchers in nanocarriers attributed to their defined structure, size, and shape. MBBs with various architectures have been proposed and constructed with well-defined domains for loading "cargos", including core, shell, and periphery functional groups. Compared with nanomaterials based on self-assembly, MBBs have lots of advantages, including facile synthesis, flexible compositions, favorable stability, and tunable size and shape, that make them a promising nanoplatform for various applications. This paper summarizes the recent progress during the past decade, with a focus on developments within the last five years in the synthesis of MBBs with different architectures, and uses them as nanocarriers in drug delivery, biological imaging, and other emerging applications.

Polysaccharides as a Hydrophilic Building Block of Amphiphilic Block Copolymers for the Conception of Nanocarriers.

Polysaccharides are gaining increasing attention for their relevance in the production of sustainable materials. In the domain of biomaterials, polysaccharides play an important role as hydrophilic components in the design of amphiphilic block copolymers for the development of drug delivery systems, in particular nanocarriers due to their outstanding biocompatibility, biodegradability, and structural versatility. The presence of a reducing end in polysaccharide chains allows for the synthesis of polysaccharide-based block copolymers. Compared with polysaccharide-based graft copolymers, the structure of block copolymers can be more precisely controlled. In this review, the synthesis methods of polysaccharide-based amphiphilic block copolymers are discussed in detail, taking into consideration the structural characteristics of polysaccharides. Various synthetic approaches, including reductive amination, oxime ligation, and other chain-end modification reactions, are explored. This review also focuses on the advantages of polysaccharides as hydrophilic blocks in polymeric nanocarriers. The structure and unique properties of different polysaccharides such as cellulose, hyaluronic acid, chitosan, alginate, and dextran are described along with examples of their applications as hydrophilic segments in the synthesis of amphiphilic copolymers to construct nanocarriers for sustained drug delivery.

Nanodiamonds: A Cutting-Edge Approach to Enhancing Biomedical Therapies and Diagnostics in Biosensing.

Nanodiamonds (NDs) have garnered attention in the field of nanomedicine due to their unique properties. This review offers a comprehensive overview of NDs synthesis methods, properties, and their uses in biomedical applications. Various synthesis techniques, such as detonation, high-pressure, high-temperature, and chemical vapor deposition, offer distinct advantages in tailoring NDs' size, shape, and surface properties. Surface modification methods further enhance NDs' biocompatibility and enable the attachment of bioactive molecules, expanding their applicability in biological systems. NDs serve as promising nanocarriers for drug delivery, showcasing biocompatibility and the ability to encapsulate therapeutic agents for targeted delivery. Additionally, NDs demonstrate potential in cancer treatment through hyperthermic therapy and vaccine enhancement for improved immune responses. Functionalization of NDs facilitates their utilization in biosensors for sensitive biomolecule detection, aiding in precise diagnostics and rapid detection of infectious diseases. This review underscores the multifaceted role of NDs in advancing biomedical applications. By synthesizing NDs through various methods and modifying their surfaces, researchers can tailor their properties for specific biomedical needs. The ability of NDs to serve as efficient drug delivery vehicles holds promise for targeted therapy, while their applications in hyperthermic therapy and vaccine enhancement offer innovative approaches to cancer treatment and immunization. Furthermore, the integration of NDs into biosensors enhances diagnostic capabilities, enabling rapid and sensitive detection of biomolecules and infectious diseases. Overall, the diverse functionalities of NDs underscore their potential as valuable tools in nanomedicine, paving the way for advancements in healthcare and biotechnology.

Sol-gel synthesis, physicochemical characteristics and in vitro pH-responsive metformin drug release of uniformly polydopamine coated mesoporous silica nanospheres

A recent attention has been paid to the repurposing potential of metformin drug for cancer chemotherapy. Herein, pH-responsive metformin drug delivery nanocarriers were achieved using sol-gel synthesized mesoporous silica nanospheres (MSN) uniformly coated with polydopamine (PDA) shell. The PDA coating shell around the MSN surface was in situ formed through oxidative self-polymerization of dopamine monomers in an alkaline solution at room temperature. The microstructure, structural and textural characteristics of PDA@MSN were examined and compared to uncoated MSN. Furthermore, PDA coated metformin (MET) drug-loaded MSN were used to study the pH-responsive MET drug release behaviour under neutral and acidic conditions. The in vitro release test showed that the PDA coating shell not only protects MET drug leakage under normal physiological conditions (pH 7.4) but also allows for its controlled/sustained release in acidic conditions (pH 4.5 and pH 5.5) which closely mimic the intracellular acidity (pH 4.5–5.5) of endosomes/lysosomes formed around drug-loaded nanocarriers after their endocytosis by cancer cells.

The capability of pure and modified boron carbide nanosheet as a nanocarrier for dacarbazine anticancer drug delivery: DFT study

The capability of pure and modified boron carbide nanosheet as a nanocarrier for dacarbazine anticancer drug delivery: DFT study

Biobased Nanomaterials: Pioneering Innovations for Biomedical Advancements.

The purpose of this review article is to provide a complete overview of the fastdeveloping topic of biobased nanomaterials and the various uses that they have. An extensive study into the utilization of biological resources for nanotechnology has been motivated by the growing demand for materials that are both sustainable and favorable to the environment. In this review, the different uses of biobased nanomaterials across a variety of fields are investigated. When it comes to drug delivery systems, biosensors, nanocarriers, and catalysts, biobased nanomaterials are interesting choices because of their unique qualities. These properties include biocompatibility, programmable surface chemistry, and inherent functionality. Also, in the biomedical field, biobased nanomaterials offer promising prospects for revolutionizing medical diagnostics and therapies. Their biocompatibility, tunable surface chemistry, and inherent functionalities make them attractive candidates for applications such as targeted drug delivery, imaging contrast agents, and tissue engineering scaffolds. In addition, the study discusses the current difficulties and potential future developments in the industry, emphasizing the necessity of interdisciplinary collaboration and ongoing innovation. The incorporation of nanomaterials derived from biological sources into conventional applications holds tremendous potential for the advancement of sustainable development and provides solutions to global concerns. For the purpose of providing researchers, scientists, and professionals with a complete grasp of the synthesis, characterization, and applications of biobased nanomaterials, the purpose of this review is to serve as a helpful resource.