Nanoparticle Drug Research Articles

Surface Modification of Metallic Nanoparticles for Targeting Drugs

This review focuses on the surface modification of metallic nanoparticles for targeted drug delivery. Metallic nanoparticles, owing to their unique size, stability, and payload capacity, have emerged as promising drug carriers. However, their application necessitates surface modification to enable precise targeting. Various strategies, such as polymer coating methods, the use of functional groups, and bio-conjugation with targeting ligands, are explored. The review also discusses the selection of ligands based on target receptors, active and passive targeting approaches, and stimuli-responsive targeting. It further delves into the challenges of translating these strategies to clinical settings, including scalability, toxicity, and regulatory hurdles. The surface modification of metallic nanoparticles is a promising avenue for targeted drug delivery. Various strategies, including polymer coating, functionalization with specific groups, and bioconjugation with targeting ligands, have been explored to enhance the therapeutic potential of these nanoparticles. The challenges in clinical translation, continuous advancements in nanoparticle synthesis, and surface modification techniques offer a positive outlook for the future of targeted metallic nanoparticle systems. Despite the promising potential of metallic nanoparticles in drug delivery, there are several challenges that need to be addressed for their successful clinical translation. These include scalable fabrication and functionalization of nanoparticles, toxicity concerns, and regulatory hurdles. However, continuous advancements in nanoparticle synthesis and surface modification techniques are expected to overcome these challenges in the near future.

Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy.

Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates. The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment. However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets. Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation. We also explored the clinical implementations of immunotherapy grounded on nanomedicine.

Bedaquiline-Loaded Solid Lipid Nanoparticles Drug Delivery in the Management of Non-Small-Cell Lung Cancer (NSCLC).

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (-) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of -0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential.

Theoretical study of the binding mechanism between anticancerous drug mercaptopurine and gold nanoparticles using a cluster model.

Mercaptopurine is an effective anticancer medicine yet known with serious adverse reactions, thus requiring further attempts to enhance its biological targeting. Small gold clusters Aun (n = 2-10) were used as model reactants to simulate the surface of gold nanoparticles. The computed results show that the drug molecules tend to anchor on the gold clusters at the S atom with the associated binding energies varying from -50 to -34 kcal mol-1 (in vacuum) and from -42 to -28 kcal mol-1 (in aqueous solution). Furthermore, the adsorption of the drug onto the gold surface is considered as a reversible process, and the mechanism of drug releasing was found to be triggerable by internal factors, such as a pH change or the concentrated presence of thiol amino acids in cancerous protein structures. Calculations based on density functional theory (DFT) were performed to probe the nature of interactions between the drug and gold nanoparticles. Structural features, thermodynamic parameters, bonding characteristics, and electronic properties of the resulting complexes were investigated at the PBE//cc-pVTZ/cc-pVDZ-PP level.

P10.22.B COMBINATION OF ARTS MIMETICS WITH AUTOPHAGY INHIBITORS AS A NOVEL THERAPEUTIC STRATEGY TO OVERCOME APOPTOSIS RESISTANCE IN GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant brain tumour in adults. The current standard of care for GBM patients consists of maximal surgical resection followed by chemotherapy and radiation. Despite such an aggressive treatment approach, the average 5-year survival rate for GBM patients is approximately 5%. One of the main reasons for poor therapy response in the GBM is resistance to programmed cell death, otherwise known as apoptosis. One of the mechanisms behind apoptosis resistance relies on the upregulation of inhibitor of apoptosis proteins (IAPs) which are known to hinder pro-apoptotic proteins and allow cell survival under abnormal conditions such as severe DNA damage. However, there are natural IAP antagonists such as ARTS which are capable of stimulating cell death by promoting the degradation of IAPs. To harness the pro-apoptotic function of IAP antagonists, small peptide mimetics of ARTS have been developed. This project investigates the efficacy of utilizing ARTS mimetics as a novel strategy to overcome apoptosis resistance in the GBM treatment. MATERIAL AND METHODS This study utilizes patient-derived cells with exogenous gain-of-function (GOF) overexpression to introduce full-length ARTS protein as well as pharmacological small peptide mimetics of ARTS to evaluate the response of GBM cells following the promotion of ARTS activity. We also employ a patient-derived orthotopic xenograft mouse model to test novel combinatorial strategies in vivo, where we used a nanoparticle drug delivery system to ensure treatment delivery across the blood-brain barrier (BBB). RESULTS We found that patient-derived GBM cells were highly resistant to ARTS-induced apoptosis. Further molecular investigation unveiled a novel role of ARTS in the upregulation of autophagy as a resistance mechanism. A combination of ARTS GOF or mimetic peptides with autophagy inhibitors mitigated resistance to ARTS-mediated apoptosis and drastically decreased GBM cell proliferation. This combination was further tested in the patient-derived xenograft mouse model, which demonstrated the successful delivery of ARTS mimetic peptides and autophagy inhibitors through the BBB via nanoparticle lipid carriers. Animals treated with a combination of the autophagy inhibitor Spautin-1 and ARTS mimetic peptides demonstrated significantly prolonged survival, confirming the therapeutic potential of such combinatorial approach for GBM treatment. CONCLUSION Altogether, these findings uncover a previously unknown role of ARTS in autophagy regulation and provide evidence that the combination of IAP-antagonist mimetics with autophagy inhibitors can be an effective strategy against highly aggressive GBM brain tumours. This work was supported by the Health Sciences Centre Foundation (HSCF).

Investigation of VEGF (rs 699947) polymorphism in the progression of Rheumatoid Arthritis (RA) and in-silico nanoparticle drug delivery of potential phytochemicals to cure RA.

Mutation in the VEGF gene disturbs the production of chondrocytes and angiogenesis which are essential for cartilage health. Cytokines and chemokines produced by auto-activation of B-cells degrade cartilage. Bruton's Tyrosine Kinase (BTK) plays a crucial role in the activation of these B-cells. VEGF has a central part in angiogenesis, in the recruitment of endothelial cells, and is involved in mechanisms that result in tumour formation. The objective of this research is to investigate the potential role of VEGF polymorphism in the development of Rheumatoid Arthritis (RA) and the screening of potential natural, synthetic BTK inhibitor compounds as possible in-silico chemotherapeutic agents to control auto-activation of B-cells and cartilage degrading cytokines. In this study, it had been shown that allele A frequency was significantly higher than that of allele C in RA-positive patients as compared to controls. Hence it depicts that allele A of VEGF (rs699947) can increase the risk of RA while allele C has a protective role. The phytochemicals which showed maximum binding affinity at the inhibitory site of BTK include beta boswellic acid, tanshinone, and baicalin. These phytochemicals as BTK inhibitor give insights to use them as anti-arthritic compounds by nanoparticle drug delivery mechanism.

"Reaction"-Like Shaping of Self-Delivery Supramolecular Nanodrugs in the Nanoprecipitation Process.

Nanoprecipitation, which is achieved through the diffusion and precipitation of drug molecules in blended solvent and antisolvent phases, is a classic route for constructing nanodrugs (NDs) and previously directed by diffusion-controlled theory. However, the diffusion-controlled mechanism is out of date in the recent preparation of self-delivery supramolecular NDs (SDSNDs), characterized by the construction of drug nanoparticles through supramolecular interactions in the absence of carriers and surfactants. Herein, a "reaction"-like complement, contributed from supramolecular interactions, is proposed for the preparation of naphthoquinone SDSNDs. Different from the diffusion-controlled process, the formation rate of SDSNDs via the "reaction"-like process is almost constant and highly dependent on the supramolecular interaction-determined Gibbs free energy of molecular binding. Thus, the formation rate and drug availability of SDSNDs are greatly improved by engineering the supramolecular interactions, which facilitates the preparation of SDSNDs with expected sizes, components, and therapeutic functions. As a deep understanding of supramolecular-interaction-involved nanoprecipitation, the current "reaction"-like protocol not only provides a theoretical supplement for classic nanoprecipitation but also highlights the potential of nanoprecipitation in shaping self-assembled, coassembled, and metal-ion-associated SDSNDs.

Bio-evaluation of poly(lactic-co-glycolic) acid nanoparticles loaded with radiolabelled rifampicin.

The poly(lactic-co-glycolic) acid (PLGA) nanoparticles of tubercular drugs have been demonstrated to have a sustained release profile over 7 days. There is no information on the location or mode of release of these nanoparticles in living systems. Therefore, we have planned the study to explore the pharmacokinetics and biodistribution of PLGA rifampicin nanoparticles in healthy human volunteers. We aim to study the distribution pattern of PLGA-loaded nano-formulation of radiolabelled rifampicin in humans. Rifampicin was labelled with 99m Tc by indirect method and nanoparticles were prepared by a single emulsion evaporation method. To investigate the pharmacokinetics and biodistribution of nanoparticles, a single dose of 450 mg of rifampicin was administered orally to healthy human volunteers divided into two different groups. Following a single oral dosage of the rifampicin nanoformulation, the pharmacokinetic (PK) parameters were significantly different between the nanoparticle and conventional groups: area under the concentration-time curve (AUC = 113.8 vs. 58.6; P < .001), mean residence time (MRT = 16.2 vs. 5.8; P < .01) and elimination rate constant (Ke = 0.04 vs. 0.10; P < .05). Also, Single-photon emission computed tomography/computed tomography (SPECT/CT) images revealed biodistribution of nanoparticles in the distal portions of the intestine, which is consistent with our dosimetry analysis. Significant difference in PK parameters and biodistribution of nanoparticles in spleen and lymph nodes with maximum deposition were observed in the large intestine. The nanoparticle distribution pattern may be advantageous for the treatment of intestinal or lymph node tuberculosis (TB) and has the potential to result in a lower dose of rifampicin nanoformulation for the treatment of pulmonary TB.

Polymeric Nanoparticles: Prospective on the Synthesis, Characterization and Applications in Nose-to-Brain Drug Delivery

Abstract: For the treatment of brain illnesses, there is growing interest in nose-to-brain drug administration. Other, more traditional methods of crossing the blood–brain barrier (BBB) are ineffective. As a result, the therapeutic concentration in the brain cannot be achieved, and the reaction is inadequate. Intranasal medication delivery is one intriguing technique for avoiding first-pass metabolism and bypassing the blood-brain barrier. It lowers medicine doses while reducing systemic side effects. Compared to conventional drug delivery platforms, a nanoparticulate drug delivery method allows for greater penetration via the nasal route. It is better to make the nanoparticles for nose-to-brain administration when a good carrier (polymers) is used. This review focuses on the many processes for creating polymeric nanoparticles, strategies and tactics for improving nose-tobrain drug delivery efficiency, and nanoparticle characterization. The use of the nose-to-brain drug delivery platform is being explored using a variety of nanoparticles created by researchers for the treatment of brain illnesses.

Advances and Opportunities in Nanoparticle Drug Delivery for Central Nervous System Disorders: A Review of Current Advances.

This narrative review provides an overview of the current advances, challenges, and opportunities in nanoparticle drug delivery for central nervous system (CNS) disorders. The treatment of central nervous system disorders is challenging due to the blood-brain barrier (BBB), which limits the delivery of therapeutic agents to the brain. Promising approaches to address these issues and improve the efficacy of CNS disease therapies are provided by nanoparticle-based drug delivery systems. Nanoparticles, such as liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles, can be modified to enhance targeting, stability, and drug-release patterns. They allow for the encapsulation of a variety of therapeutic compounds and can be functionalized with ligands or antibodies for active targeting, minimizing off-target effects. Additionally, nanoparticles can circumvent drug resistance processes and provide versatile platforms for applications that combine therapeutic and diagnostic functions. Although the delivery of CNS medications using nanoparticles has advanced significantly, there are still challenges to be resolved. These include understanding the BBB interactions, doing long-term safety studies, and scaling up the production. However, improvements in nanotechnology and a deeper comprehension of CNS disorders provide opportunities to enhance treatment results and address unmet medical requirements. Future research and ongoing clinical trials are required to further explore the potential of nanoparticle drug delivery for CNS disorders.

Nano-calcipotriol as a potent anti-hepatic fibrosis agent.

Calcipotriol (CAL) has been widely studied as a fibrosis inhibitor and used to treat plaque psoriasis via transdermal administration. The clinical application of CAL to treat liver fibrosis is bottlenecked by its unsatisfactory pharmacokinetics, biodistribution, and side effects, such as hypercalcemia in patients. The exploration of CAL as a safe and effective antifibrotic agent remains a major challenge. Therefore, we rationally designed and synthesized a self-assembled drug nanoparticle encapsulating CAL in its internal hydrophobic core for systematic injection (termed NPs/CAL) and further investigated the beneficial effect of the nanomaterial on liver fibrosis. C57BL/6 mice were used as the animal model, and human hepatic stellate cell line LX-2 was used as the cellular model of hepatic fibrogenesis. Immunofluorescence staining, flow cytometry, western blotting, immunohistochemical staining, and in vitro imaging were used for evaluating the efficacy of NPs/CAL treatment. We found NPs/CAL can be quickly internalized in vitro, thus potently deactivating LX-2 cells. In addition, NPs/CAL improved blood circulation and the accumulation of CAL in liver tissue. Importantly, NPs/CAL strongly contributed to the remission of liver fibrosis without inducing hypercalcemia. Overall, our work identifies a promising paradigm for the development of nanomaterial-based agents for liver fibrosis therapy.

Potential therapeutic effects of naringin loaded PLGA nanoparticles for the management of Alzheimer's disease: In vitro, ex vivo and in vivo investigation

BackgroundAlzheimer's disease (AD) is the most prevalent type of dementia which has been affected to more the 44 million people globally. It is distinguished by gradually deteriorating memory and other cognitive abilities that precede dementia. Present treatment of AD mainly focuses on symptomatic slowing the evolution of the disease which is associated with numerous side effects such as dizziness, tiredness, nausea, vomiting, heart attack, and stroke etc. Henceforth; there is urgent need to identify the alternative treatment for management of AD. Herbal medicines have been used from long time to treat AD. One of such leading Phyto molecule is Naringin. It showed promising results against AD but suffers from poor bioavailability and require in high dose to cross the blood brain barrier. ObjectivesThe main objectives of proposed work are to increase the bioavailability of naringin in brain by developing Nano-suspension and preclinical evaluation of neuroprotective effect of Naringin Nano-suspension (NNS) against Scopolamine induced Alzheimer's disease in rats. MethodsThe present study deals with the development, characterization of NNSand to evaluate neuroprotective effect of NNS. Nanoparticles of drug were formed by using PLGA polymer and optimized by using 32 factorial design. Optimized batch was further characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). Further the effectiveness of NNS was preclinically investigated by performing AOTstudy as per OECD guideline 420. AD induced Albino Wistar Rats were treated with NNS orally for 14 days and then evaluated for parameters like Gross examination of brain, Relative brain weight determination, behavioural parameters, neuro-inflammatory parameters and immune-histology. ResultsOptimization was carried out to study the effect of polymer concentration and number of HPH cycles on Particle size, Poly dispersity index (PDI) and % entrapment efficiency. Desirability search approach was used to select the optimized formulation. Based on the selection criteria, batch F6 having 357.6 ± 05 nm particle size, 0.168 ± 0.04 PDI and 91 ± 2% EE was selected as optimized batch. SEM analysis showed spherical morphology and XRD confirmed the molecular dispersion. Pre-treatment with NNS showed neuroprotective activity basedon results of behavioural studies, biochemical estimation, neuroinflammatory parameters and immunohistochemistry evaluations. ConclusionAs NNS showed significant neuroprotective and anti-neuro-inflammatory effect, this study opens up new ways to exploit Naringin for various therapeutic and restorative purposes.

Formulation and Scale-up of Delamanid Nanoparticles via Emulsification for Oral Tuberculosis Treatment.

Delamanid (DLM) is a hydrophobic small molecule therapeutic used to treat drug-resistant tuberculosis (DR-TB). Due to its hydrophobicity and resulting poor aqueous solubility, formulation strategies such as amorphous solid dispersions (ASDs) have been investigated to enhance its aqueous dissolution kinetics and thereby improve oral bioavailability. However, ASD formulations are susceptible to temperature- and humidity-induced phase separation and recrystallization under harsh storage conditions typically encountered in areas with high tuberculosis incidence. Nanoencapsulation represents an alternative formulation strategy to increase aqueous dissolution kinetics while remaining stable at elevated temperature and humidity. The stabilizer layer coating the nanoparticle drug core limits the formation of large drug domains by diffusion during storage, representing an advantage over ASDs. Initial attempts to form DLM-loaded nanoparticles via precipitation-driven self-assembly were unsuccessful, as the trifluoromethyl and nitro functional groups present on DLM were thought to interfere with surface stabilizer attachment. Therefore, in this work, we investigated the nanoencapsulation of DLM via emulsification, avoiding the formation of a solid drug core and instead keeping DLM dissolved in a dichloromethane dispersed phase during nanoparticle formation. Initial emulsion formulation screening by probe-tip ultrasonication revealed that a 1:1 mass ratio of lecithin and HPMC stabilizers formed 250 nm size-stable emulsion droplets with 40% DLM loading. Scale-up studies were performed to produce nearly identical droplet size distribution at larger scale using high-pressure homogenization, a continuous and industrially scalable technique. The resulting emulsions were spray-dried to form a dried powder, and in vitro dissolution studies showed dramatically enhanced dissolution kinetics compared to both as-received crystalline DLM and micronized crystalline DLM, owing to the increased specific surface area and partially amorphous character of the DLM-loaded nanoparticles. Solid-state NMR and dissolution studies showed good physical stability of the emulsion powders during accelerated stability testing (50 °C/75% RH, open vial).

Application of Nanoparticle Drug Delivery Systems in the Medical Field: Focusing on Functionalized Gold Nanomaterials

Nanoparticle drug delivery systems are currently one of the hottest topics in the field of medicine. They can precisely deliver drugs to the parts of the patient that need treatment, with the goal of improving patient effectiveness and reducing drug toxicity. Gold nanoparticles (AuNPs) are considered one of the most promising nanomaterials due to their unique optical, electronic, sensing, and biochemical properties. By combining AuNPs with different ligands, functionalized gold nanoparticle (F-AuNPs) drug delivery systems can be obtained, which have broad application prospects in the field of medicine. This article focuses on the different ligand connection types of F-AuNPs and reviews the research progress of F-AuNPs drug delivery systems in the field of medicine in recent years.

Orthogonal Gelations to Synthesize Core-Shell Hydrogels Loaded with Nanoemulsion-Templated Drug Nanoparticles for Versatile Oral Drug Delivery.

Hydrophobic active pharmaceutical ingredients (APIs) are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual-responsive gelation process that exploits orthogonal thermo-responsive and ion-responsive gelations is introduced. This one-step "dual gelation" synthesizes core-shell (methylcellulose-alginate) hydrogel particles and encapsulates drug-laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed-dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core-shell hydrogel particles.

Modification of Poly(Glycerol Adipate) with Tocopherol and Cholesterol Modulating Nanoparticle Self-Assemblies and Cellular Responses of Triple-Negative Breast Cancer Cells to SN-38 Delivery.

This study aimed to fabricate new variations of glycerol-based polyesters by grafting poly(glycerol adipate) (PGA) with hydrophobic bioactive moieties, tocopherol (TOC), and cholesterol (CHO). Their effects on nanoparticle (NP) formation, drug release, and cellular responses in cancer and normal cells were evaluated. CHO and TOC were successfully grafted onto PGA backbones with 30% and 50% mole grafting. Increasing the percentage of mole grafting in both molecules increased the glass transition temperature and water contact angle of the final polymers but decreased the critical micelle concentration of the formulated particles. PGA-TOC NPs reduced the proliferation of MDA-MB-231 cancer cells. However, they enhanced the proliferation of primary dermal fibroblasts within a specific concentration range. PGA-CHO NPs minimally affected the growth of cancer and normal cells. Both types of NPs did not affect apoptosis or the cell cycle of cancer cells. PGA-CHO and PGA-TOC NPs were able to entrap SN-38, a hydrophobic anticancer drug, with a particle size <200 nm. PGA-CHO NPs had a higher drug loading capacity and a greater drug release than PGA-TOC NPs. However, SN-38-loaded PGA-TOC NPs showed higher toxicity than SN-38 and SN-38-loaded PGA-CHO NPs due to the combined effects of antiproliferation and higher cellular uptake. Compared with SN-38, the drug-loaded NPs more profoundly induced sub-G1 in the cell cycle analysis and apoptosis of cancer cells in a similar pattern. Therefore, PGA-CHO and PGA-TOC polymers have potential applications as delivery systems for anticancer drugs.

Synthesis and evaluation of cross-linked gelatin nanoparticles for controlled release of an anti-diabetic drug: Gliclazide

The main problem with oral drug delivery using gelatin is rapid dissolution in aqueous mediums, which results in high-speed drug release. In the present study to overcome the challenge, we used glutaraldehyde to cross-link gelatin in order to control the burst release of drug. A drug delivery system based on gelatin nanoparticles (GNPs) for carrying Gliclazide was prepared by a two-step dissolution method. FTIR spectrum showed the presence of an aldimine functional group in GNPs, which confirms that gelatin structure is cross-linked by glutaraldehyde. XRD pattern showed that the crystallinity and crystal size of GNPs were 8% and 73 nm, respectively. SEM images showed the cross-linked structure of GNPs by glutaraldehyde, and DLS analysis exhibited an average particle size of about 88 nm. Ninhydrin assay showed the GNPs completely cross-linked for all ratios of gelatin to cross-linker (8%v/v, 16%v/v, and 25%v/v). After 8 h, the highest and lowest swelling percentages were related to cross-linked samples with 8%v/v and 25%v/v glutaraldehyde (in PBS buffer, pH=7.4, and 37 °C), respectively. The nanoparticle yield and drug loading were optimized via cross-linker concentration and GNPs: GLI ratio. The drug-release behavior from GNPs was controlled by the degree of swelling. The results showed that cross-linked GNPs via 8 %v/v and 25%v/v glutaraldehyde had the highest and lowest GLI release, (70% and 34% after 480 min, respectively, in PBS buffer, pH=7.4, and 37 °C). GLI release from GNPs showed controlled behavior compared with commercial anti-diabetic drugs, including Diabezide 80 mg and Diamicron MR 30 mg. MTT assay results showed that 94.5% of cells in contact with GLI-loaded GNPs survived.

Nanoparticle: A unique strategy for Antifungal agents.

Nanomaterials are emerging as an innovative and efficient instrument for the transport and cellular translocation of therapeutic compounds, namely, biopharmaceuticals. The use of nanoparticles as drug carriers in the healthcare industry, for instance, in several applications, with drug delivery being among the most significant. These nanomaterials are adaptable and have qualities that are good for delivering compounds that are biologically active. The creation of different nanoparticles as a drug delivery system has led to the development of a variety of nanoparticulate drug delivery systems to reduce toxicity, reduce the dosing system, and increase the viability of the drug. The objectives of this review are to provide an overview of the recent advances in nanotechnology in Antifungal treatment and to overcome the problems associated with antifungal agents.

Oyster ferritin can efficiently alleviate ROS-mediated inflammation attributed to its unique micro-environment around three-fold channels.

The conversion of toxic Fe2+ into non-toxic Fe3+ stored in the inner cavity of ferritin nanocage could effectively reduce the occurrence of the Fenton reaction and inhibit the formation of harmful reactive oxygen species (ROS). In this study, we reveal that oyster ferritin (GF1) can rely on its high catalytic activity (7.7 times that of rHuHF) and high binding ability of Fe2+ (9.1 times that of rHuHF) to reduce the precursors of Fenton reaction, thus inhibiting the occurrence of Fenton reaction and slowing down reactive oxygen species-mediated inflammation. The above significant advantage of GF1 can be attributed to the Asp at the position 120th, which could increase the negatively charged area of three-fold channels from 37.8% (rHuHF) to 67.8% and then enhance its oxidation rate and ability of GF1. The findings are of great value in advancing novel nanoparticle drug design based on crystalline structure.

Formulation Development and Evaluation of Dry Adsorbed Nanoparticles of Curcumin and Piperine Dual Drug Loaded Nanostructured Lipid Carriers

Purpose: The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of curcumin (CUR) and piperine (PIP) loaded nanostructured lipid carriers (NLCs). Methods: CUR and PIP-loaded NLCs (CP NLCs) were prepared by modified hot-melt emulsification using precirol ATO5 (PRE) as solid lipid, labrafac lipophile WL1349 (LAF) as liquid lipid, and a combination of tween 80 (T80) with gelucire 50/13 (G50/13) as surfactants. The NLCs system was subjected to physical stability, particle size, zeta potential, thermal behaviour, crystallinity study and in-vitro drug release. Further, an evaporative drying technique converted the NLC system into stable DANs by adsorbing onto mannitol (Pearlitol 200SD). The DANs were characterized for redispersion properties, particle size, flow properties and in-vitro drug release. The stability studies were carried out for 30 days. Results: The optimized CP NLCs were of imperfect type and had a mean particle size of 248.5 ± 12.8 nm (size distribution of 0.216 ± 0.021), a zeta potential of -9.03 ± 0.53 mV, an entrapment efficiency (EE) of 99.80 ± 0.21% (CUR), 100.05 ± 0.07% (PIP) with a drug recovery of 99.70 ± 0.21% (CUR) and 100.36 ± 0.12% (PIP). The X-ray diffraction pattern and endothermic peaks confirmed the encapsulation of actives in lipid matrices. The in-vitro drug release showed controlled release for 24 h. The optimized DANs led to maximum redispersion and retained a particle size of 268.4 ± 23.1 nm (distribution 0.235 ± 0.037) with controlled release similar to CP NLCs. The CP NLCs DANs showed reasonable stability for 30 days. Conclusions: The developed CP NLCs DANs showed a controlled release profile, and the adsorption technique can be used to improve the stability of NLC dispersion. The DANs can be offered in patient-friendly dosage forms such as sachets, capsules, and compressed tablets.