Drug Nanocarriers Research Articles

Exosomes as a Nano-Carrier for Chemotherapeutics: A New Era of Oncology.

Despite the considerable advancements in oncology, cancer remains one of the leading causes of death worldwide. Drug resistance mechanisms acquired by cancer cells and inefficient drug delivery limit the therapeutic efficacy of available chemotherapeutics drugs. However, studies have demonstrated that nano-drug carriers (NDCs) can overcome these limitations. In this sense, exosomes emerge as potential candidates for NDCs. This is because exosomes have better organotropism, homing capacity, cellular uptake, and cargo release ability than synthetic NDCs. In addition, exosomes can serve as NDCs for both hydrophilic and hydrophobic chemotherapeutic drugs. Thus, this review aimed to summarize the latest advances in cell-free therapy, describing how the exosomes can contribute to each step of the carcinogenesis process and discussing how these nanosized vesicles could be explored as nano-drug carriers for chemotherapeutics.

Active Transport and Ocular Distribution of Intravitreally Injected Liposomes.

Drug delivery to the retina remains a challenge due to ocular barriers and fast clearing mechanisms. Nanocarrier drug delivery systems (NDDSs) hold the promise of prolonging intraocular retention times and increasing drug concentrations in the retina. Anionic and cationic PEGylated liposomes, loaded with oxaliplatin (OxPt) to be used as trace element, were prepared from dry lipid powders. The differently charged liposomes were intravitreally injected in C57BL/6JrJ mice; eyes were harvested 2hours and 24hours post-injection. To investigate active transport mechanisms in the eye, a subset of mice were pre-injected with chloroquine before injection with cationic liposomes. Eyes were dissected and the distribution of OxPt in different tissues were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Both liposome formulations enhanced the retention time of OxPt in the vitreous over free OxPt. Surprisingly, when formulated in cationic liposomes, OxPt translocated through the retina and accumulated in the RPE-sclera. Pre-injection with chloroquine inhibited the transport of liposomal OxPt from the vitreous to the RPE-sclera. We show that liposomes can enhance the retention time of small molecular drugs in the vitreous and that active transport mechanisms are involved in the trans retinal transport of NDDS after intravitreal injections. These results highlight the need for understanding the dynamics of ocular transport mechanisms in living eyes when designing NDDS with the back of the eye as the target. Active transport of nanocarriers through the retina will limit the drug concentration in the neuronal retina but might be exploited for targeting the RPE.

New cage-based imine and ester linked COF as a smart nanocarrier drug delivery system

New cage-based imine and ester linked COF as a smart nanocarrier drug delivery system

Biocatalytic synthesis of new polyesteramides from ε-caprolactam and hydroxy acids: Structural characterization, biodegradability, and suitability as drug nanocarriers

The synthesis of polyesters and polyamides by enzyme-catalyzed processes in vitro was developed in the last decades as a green alternative to obtain biodegradable synthetic polymers with various applications, such as nanoparticle-sized carriers for drug delivery. Polyesteramides were much less studied in this respect, although having the presumable advantage of increased mechanical and thermic resistance brought by the amide moieties. In this work, polyesteramides were synthesized for the first time employing as raw materials ε-caprolactam and a hydroxy acid. L-malic, 3-hydroxybutyric, 12-hydroxystearic and 16-hydroxyhexadecanoic acid, respectively, were investigated as co-monomers in solventless or organic medium, using the immobilized lipase Novozyme 435 as catalyst. The short chain hydroxy acids holding secondary hydroxyl groups yielded oligomers with average degree of polymerization no higher than 4, while in the case of the long-chain 12-hydroxystearic acid this value increased to 7. The best results were achieved by using 16-hydroxyhexadecanoic acid in 2:1 M excess at 80 °C, yielding a product with 75% copolymer content and average molecular weight higher than 3000 Da. The emulsion-solvent evaporation method allowed the efficient production of nanoparticles based on this copolymer, with sizes around 230 nm, used for the encapsulation of a model bioactive compound, the anticancer drug sorafenib. Production yields of >70% and encapsulation efficiencies of around 60% are very promising for further development of this approach.

Targeting macrophage M1 polarization suppression through PCAF inhibition alleviates autoimmune arthritis via synergistic NF-κB and H3K9Ac blockade

Sustained inflammatory invasion leads to joint damage and progressive disability in several autoimmune rheumatic diseases. In recent decades, targeting M1 macrophage polarization has been suggested as a promising therapeutic strategy for autoimmune arthritis. P300/CBP-associated factor (PCAF) is a histone acetyltransferase (HAT) that exhibits a strong positive relationship with the proinflammatory microenvironment. However, whether PCAF mediates M1 macrophage polarization remains poorly studied, and whether targeting PCAF can protect against autoimmune arthritis in vivo remains unclear. Commonly used drugs can cause serious side effects in patients because of their extensive and nonspecific distribution in the human body. One strategy for overcoming this challenge is to develop drug nanocarriers that target the drug to desirable regions and reduce the fraction of drug that reaches undesirable targets. In this study, we demonstrated that PCAF inhibition could effectively inhibit M1 polarization and alleviate arthritis in mice with collagen-induced arthritis (CIA) via synergistic NF-κB and H3K9Ac blockade. We further designed dextran sulfate (DS)-based nanoparticles (DSNPs) carrying garcinol (a PCAF inhibitor) to specifically target M1 macrophages in inflamed joints of the CIA mouse model via SR-A–SR-A ligand interactions. Compared to free garcinol, garcinol-loaded DSNPs selectively targeted M1 macrophages in inflamed joints and significantly improved therapeutic efficacy in vivo. In summary, our study indicates that targeted PCAF inhibition with nanoparticles might be a promising strategy for treating autoimmune arthritis via M1 macrophage polarization inhibition.

Transfersome, an ultra-deformable lipid-based drug nanocarrier: an updated review with therapeutic applications.

The application of nanotechnology with integration of chemical sciences is increasing continuously in the management of diseases. The drug's physicochemical and pharmacological characteristics are enhanced by application of nanotechnological principles. Several nanotechnology-based formulations are being investigated to improve patient compliance. One such novel nanocarrier system is transfersome (TFS) and is composed of natural biocompatible phospholipids and edge activators. Morphologically, TFS are similar to liposomes but functionally, these are ultra-deformable vesicles which can travel through pores smaller than their size. Because of their amphipathic nature, TFS have the potential to deliver the drugs through sensitive biological membranes, especially the blood-brain barrier, skin layers, and nasal epithelium. Different molecular weight drugs can be transferred inside the cell by encapsulation into the TFS. Knowing the tremendous potentiality of TFS, the present work provides an in-depth and detailed account (pharmaceutical and preclinical characteristics) of TFS incorporating different categories of therapeutic moieties (anti-diabetic, anti-inflammatory, anti-cancer, anti-viral, anti-fungal, anti-oxidant, cardiovascular drugs, CNS acting drugs, vaccine delivery, and miscellaneous applications). It also includes information about the methods of preparation employed, significance of excipients used in the preparation, summary of clinical investigations performed, patent details, latest investigations, routes of administration, challenges, and future progresses related to TFS.

Biocompatible Snowman-like Dimer Nanoparticles for Improved Cellular Uptake in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive types of human cancers. Although paclitaxel (PTX) was proven to exert potent anti-tumor effects against ICC, the delivery of PTX is still challenging due to its hydrophobic property. Nanoparticle (NP)-based carriers have been proven to be effective drug delivery vehicles. Among their physicochemical properties, the shape of NPs plays a crucial role in their performance of cellular internalization and thus anti-tumor efficacy of loaded drugs. In this study, dumbbell-like and snowman-like dimer NPs, composed of a polylactic acid (PLA) bulb and a shellac bulb, were designed and prepared as drug nanocarriers to enhance the efficiency of cellular uptake and anti-tumor performance. PLA/shellac dimer NPs prepared through rapid solvent exchange and controlled co-precipitation are biocompatible and their shape could flexibly be tuned by adjusting the concentration ratio of shellac to PLA. Drug-loaded snowman-like PLA/shellac dimer NPs with a sharp shape exhibit the highest cellular uptake and best cell-killing ability against cancer cells in an in vitro ICC model over traditional spherical NPs and dumbbell-like dimer NPs, as proven with the measurements of flow cytometry, fluorescent confocal microscopy, and the CCK8 assay. The underlying mechanism may be attributed to the lower surface energy required for the smaller bulbs of snowman-like PLA/shellac dimer NPs to make the initial contact with the cell membrane, which facilitates the subsequent penetration through the cellular membrane. Therefore, these dimer NPs provide a versatile platform to tune the shape of NPs and develop innovative drug nanocarriers that hold great promise to enhance cellular uptake and therapeutic efficacy.

Nanogels as novel drug nanocarriers for CNS drug delivery.

Nanogels are highly recognized as adaptable drug delivery systems that significantly contribute to improving various therapies and diagnostic examinations for different human diseases. These three-dimensional, hydrophilic cross-linked polymers have the ability to absorb large amounts of water or biological fluids. Due to the growing demand for enhancing current therapies, nanogels have emerged as the next-generation drug delivery system. They effectively address the limitations of conventional drug therapy, such as poor stability, large particle size, and low drug loading efficiency. Nanogels find extensive use in the controlled delivery of therapeutic agents, reducing adverse drug effects and enabling lower therapeutic doses while maintaining enhanced efficacy and patient compliance. They are considered an innovative drug delivery system that highlights the shortcomings of traditional methods. This article covers several topics, including the involvement of nanogels in the nanomedicine sector, their advantages and limitations, ideal properties like biocompatibility, biodegradability, drug loading capacity, particle size, permeability, non-immunological response, and colloidal stability. Additionally, it provides information on nanogel classification, synthesis, drug release mechanisms, and various biological applications. The article also discusses barriers associated with brain targeting and the progress of nanogels as nanocarriers for delivering therapeutic agents to the central nervous system.

Gold nanoparticle-based drug nanocarriers as a targeted drug delivery system platform for cancer therapeutics: a systematic review

Gold nanoparticle-based drug nanocarriers as a targeted drug delivery system platform for cancer therapeutics: a systematic review

Design of carrageenan based nanocarrier as a drug nanocarrier for tumor targeting: Radiolabeling and biodistribution

Since anti-cancer drugs damage healthy tissues, targeted therapy, especially in cancer treatment, is becoming more important. Thus, many studies have examined delivery systems to mitigate these effects. Carrageenan/poly(N-isopropylacrylamide) (CAR-PNIPAm) based nanocarriers for the delivery of Doxorubicin (DOX) drugs were prepared and characterized in this study. Gamma irradiation was used to create the nanocarriers, while FT-IR, AFM, and DLS were used to characterize them. Particle size was studied in relation to irradiation dose (10–50 kGy) and total polymer content (0.5, 1.0, and 1.5wt%). At pH 5.6 and 7.2, the nanocarrier's DOX-releasing behavior was studied. According to our findings, the smallest particle size (71nm) and zeta potential (−13.2mV) were found in nanocarriers produced with 40kGy and 1wt% of CAR-PNIPAm. The zeta potential shifted to a more stable −30mV after DOX injection. pH was shown to have an effect on the rate at which DOX was released from the nanocarrier. DOX/CAR-PNIPAm nanocarriers efficiently suppressed HepG-2 and MCF-7 cancer cell lines, according to in vitro experiments. In vivo biodistribution experiments were also performed in both normal and solid tumor-bearing mice using a radiolabeled 99mTc-DOX/CAR-PNIPAm nanocarrier. A greater T/NT ratio and cell targeting were seen 30 minutes post-injection in the solid tumour model, demonstrating that the nanocarrier demonstrated tumor targeting potential. In conclusion, our results lend credence to the feasibility of 99mTc-DOX/CAR-PNIPAm nanocarrier for use in therapeutic and diagnostic settings aimed at targeting tumors.

Synthesis & characterization of novel MIP with RAFT polymerization of (2-hydroxy ethyl methacrylate)/chitosan as a nanocarrier for drug delivery applications

The primary function of the drug delivery system is to transfer various drugs to certain parts of the body. The drug is transferred reliably in the molecularity imprinted system, based on adjusting the drug release mechanism to control the drug amount and treatment duration. Molecular Imprinting Technology can provide an efficient polymer system to detect bioactive molecules and has high adsorption capacity as drug delivery carriers. This study developed a nanocarrier of molecular imprinted polymer (MIP) of poly (2-hydroxy ethyl methacrylate)/chitosan nanocomposite and also evaluated their performance for drug loading and release in the buffer blood medium. Nanocarriers were prepared based on the RAFT polymerization technique, and cefixime was applied to evaluate the load and release of drugs in nanocarriers. Crucial parameters such as the ratio of imprinted to functional monomer and also the ratio of functional monomer to cross-link should be assessed to obtain the best performance of the MIP. Each of these parameters was studied for four different ratios. TEM analysis showed that the particle size of optimum MIP was between 15 and 20 nm. The specific surface area of CH-CEMIP (chitosan-cefixime MIP) and CEMIP (cefixime MIP) samples were 7.53 and 6.32 m2/g, respectively. Comparing these amounts and the specific surface area of the (Non-Imprinted) NIP sample (1.87 m2/g) indicated that special diagnostic pores were generated. In the drug loading process, the CH-CEMIP sample with 82 mg/g could link to the drug more than CEMIP and NIP samples due to its high selectivity property. Furthermore, according to the drug release experiments, the CH-CEMIP sample performed better in 250 h as 84 % of cefixime in this duration was released slowly and steadily.

A novel intra-tumoral drug delivery carrier for treatment of oral squamous cell carcinoma

The treatment of oral squamous cell carcinoma (OSCC) includes systemic chemotherapy and is associated with aggressive side effects on patients. This study evaluated a new intra-tumor-targeted drug delivery method for the treatment of OSCC induced on the dorsum of the tongue in white mice. The induced tumors were examined by needle biopsy. A targeted anticancer drug (Cetuximab) and [Cisplatin and 5 Fluorouracil (5-FU)] chemotherapeutic agents were loaded on polyethylene glycol-polylactide-polyethylene glycol (PEG-PLA-PEG) nanoparticles (NPs) designed for intralesional injection while systemic administration was used as control. Fourier transform infrared spectroscopy (FTIR) was performed to study NP chemical structure, a drug release profile was conducted to study release kinetics, and histopathological evaluation was performed before and after treatment to evaluate tissue reactions (n-28, ά = 0.05). The drug release profile was characteristic of the chemotherapeutic agent showing early quick ascend followed by sustained slow release. FTIR peaks identified the polymeric structure of the drug nano-carrier. Histopathologic examination of chemically induced OSCC revealed different grades ranging from non-invasive to invasive stages of OSCC. Intra-tumoral test group revealed significant remission of observed cancer grade compared to the systemically administered group (X2 = 12.63, P < 0.001). Finally, using synthesized PEG–PLA–PEG NPs for intralesional injection is a promising route for the treatment of OSCC.

Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release.

Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (1O2) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with 1O2 responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates 1O2-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of 1O2. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications.

NANOPARTICLES USAGE IN THE TREATMENT OF CANCER.

Nanotechnology is an emerging scientific field that allows manipulation of the environment at the atomic and molecular level. The term cancer is given to a group of diseases whose main characteristic is the rapid multiplication of abnormal cells. Conventional treatments used for cancer are based mainly on the use of chemotherapy, radiotherapy, and surgeries, nonspecific treatments concerning target cells, because antineoplastic drugs can reach normal cells, especially those that have constant renewal, causing adverse reactions. Nanomedicine, when focused on cancer treatment, offers patients an alternative and less invasive form of treatment. Its mechanism is done utilizing drug nanocarriers, which offer flexibility in dosage and release kinetics. Even with several articles demonstrating the potential advantages of nanoparticles over diseases, this technique encounters several clinical challenges concerning their development. Thus, the combination of advances in nanotechnology and biomaterial development becomes the most promising hope for the survival of cancer patients. This study aimed to explain briefly the factors related to cancer by focusing on the applications of nanoparticles in the treatment and diagnosis of the same. It is also important to highlight that this study will describe its benefits compared to conventional pharmacotherapy.

Temozolomide and chloroquine co-loaded mesoporous silica nanoparticles are effective against glioma

The past decades have witnessed great progress in nanoparticle‐based cancer‐targeting drug delivery systems, but their therapeutic potentials is yet to be fully exploited. In this research, temozolomide (TMZ) and chloroquine (CQ) were loaded into the mesoporous silica nanoparticles (MSNs), the surface was coated with polydopamine (PDA), and the complex was coupled with arginine-glycine-aspartic (RGD) to successfully prepare TMZ/CQ@MSN-RGD. RGD-MSNs accumulated more in the cell and tumor models than in unmodified MSNs in the in vitro and in vivo experiments and can directly induce apoptosis and autophagy in tumor cells. In addition, TMZ/CQ@MSN-RGD therapy enhanced the apoptosis effect of the RGD-MSNs in glioma. Therefore, the combination of autophagy inhibitor with chemotherapy drugs in nanocarriers may promote therapeutic efficacy in treating glioma.

Biodegradable polyphosphoester micelles act as both background-free 31P magnetic resonance imaging agents and drug nanocarriers

In vivo monitoring of polymers is crucial for drug delivery and tissue regeneration. Magnetic resonance imaging (MRI) is a whole-body imaging technique, and heteronuclear MRI allows quantitative imaging. However, MRI agents can result in environmental pollution and organ accumulation. To address this, we introduce biocompatible and biodegradable polyphosphoesters, as MRI-traceable polymers using the 31P centers in the polymer backbone. We overcome challenges in 31P MRI, including background interference and low sensitivity, by modifying the molecular environment of 31P, assembling polymers into colloids, and tailoring the polymers’ microstructure to adjust MRI-relaxation times. Specifically, gradient-type polyphosphonate-copolymers demonstrate improved MRI-relaxation times compared to homo- and block copolymers, making them suitable for imaging. We validate background-free imaging and biodegradation in vivo using Manduca sexta. Furthermore, encapsulating the potent drug PROTAC allows using these amphiphilic copolymers to simultaneously deliver drugs, enabling theranostics. This first report paves the way for polyphosphoesters as background-free MRI-traceable polymers for theranostic applications.

Green nanoarchitectonics of carbon quantum dots from Cinchona Pubescens Vahl as targeted and controlled drug cancer nanocarrier

Carbon quantum dots (CQDs) are a new carbon-based nanomaterial that has attracted tremendous attention due to their excellent fluorescent properties, chemical stability, water solubility, and biocompatibility features. Here, fluorescent CQDs synthesized by a green nanoarchitectonic method using Cinchona Pubescens Vahl extract were evaluated as drug nanocarriers for carboplatin (CBP) delivery. The characterization methods showed CQDs with semispherical shapes and sizes around 5 nm, temperature- and pH-dependent functional groups that interact with the CBP molecule adding specificity to the drug-delivery system. Based on the load efficiency results, it seems that the CQDs can carry almost 100 μg of carboplatin for every 1 mg of CQDs. This is possible due to the self-assembly process that takes place through the interaction between the protonation/deprotonation functional groups of CQDs and the hydrolyzed CBP molecule. Through this process, it is created spherical nanoparticles with an average size of 77.44 nm. The CQDs-CBP nanoparticles release the drug through a diffusion-controlled release mechanism where the acidic media is preferred, and the EPR effect also plays a helpful role. Besides, the viability test shows that the CQDs have almost null cytotoxicity suggesting that they could be used as a promising cancer treatment, improving the efficiency of cell internalization and significantly increasing their drug delivery.

Evaluation of the toxicity and cisplatin drug release ability of nanocomposites of polyethylene glycol and carbon nanotubes functionalized with Zn2+ ions

Carbon nanotubes (CNTs) have been used to prepare drug nanocarriers. Zinc (Zn) ions play a crucial role in biological processes. Polyethylene glycol (PEG) is a biopolymer used in the medical field. In this work, the synthesis of ion Zn-ion-functionalized CNTs/PEG nanocomposites is described. The prepared nanocomposites were characterized using the FE-SEM, FT-IR, XPS, and DSC techniques. The ability of the prepared nanocomposites to release the anticancer drug cisplatin (CP) was assessed. The cytotoxicity of the studied nanocomposites loaded or unloaded with CP toward HeLa cells was evaluated, and their capacity to inhibit the growth of the bacteria Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa was determined. The cytotoxicity tests show that HeLa cells showed considerably larger decrease in cell viability owing to exposure to CP compared to that owing to exposure to Zn-ion-functionalized CNTs/PEG nanocomposites.

Functionalized Metal Nanoparticles in Cancer Therapy.

Currently, there are many studies on the application of nanotechnology in therapy. Metallic nanoparticles are promising nanomaterials in cancer therapy; however, functionalization of these nanoparticles with biomolecules has become relevant as their effect on cancer cells is considerably increased by photothermal and photodynamic therapies, drug nanocarriers, and specificity by antibodies, resulting in new therapies that are more specific against different types of cancer. This review describes studies on the effect of functionalized palladium, gold, silver and platinum nanoparticles in the treatment of cancer, these nanoparticles themselves show an anticancer effect. This effect is further enhanced when the NPs are functionalized with either antibodies, DNA, RNA, peptides, proteins, or folic acid and other molecules. These NPs can penetrate the cell and accumulate in the tumor tissue, resulting in a cytotoxic effect through the generation of ROS, the induction of apoptosis, cell cycle arrest, DNA fragmentation, and a photothermal effect. NP-based therapy is a new strategy that can be used synergistically with chemotherapy and radiotherapy to achieve more effective therapies and reduce side effects.

Green Synthesising ZnO Nanoparticle Using Sesbania grandiflora and Their Evaluation of Anti-diabetic Anti-advanced Glycation End Products and Cytotoxic Effects.

Nanotechnology is an emerging area of science with diverse implementations, including medicine and drug delivery. Often for drug delivery, nanoparticles and nanocarriers were used. Diabetes mellitus is a metabolic disease with numerous complications, including advanced glycation end products (AGEs). AGEs advance neurodegeneration, obesity, renal dysfunction, retinopathy, and many more. Here, we have used zinc oxide nanoparticles synthesised with Sesbania grandiflora (hummingbird tree). ZnO nanoparticles and S. grandiflora are known for their biocompatibility and medicinal property, such as anti-cancer, anti-microbial, anti-diabetic, and anti-oxidant. So, we analysed the anti-diabetic, anti-oxidant, anti-AGEs, and cytotoxic effects of green synthesised and characterised ZnO nanoparticles with S. grandiflora (SGZ) and the leaf extract of S. grandiflora. Characterisation results indicated the synthesis of ZnO Nps at maximum concentration; the anti-oxidant assay showed 87.5% free radicle scavenging with DPPH. Additionally, anti-diabetic (72% α-amylase and 65% of α-glucosidase inhibition) and cell viability also exhibited promising results. In conclusion, SGZ can reduce the absorption of carbohydrates from the diet, elevate glucose uptake, and prevent protein glycation. So, it could be a potential tool for treating diabetes, hyperglycemia, and AGE-related diseases.