MCT4 knockdown by tumor microenvironment-responsive nanoparticles remodels the cytokine profile and eradicates aggressive breast cancer cells.

Breast cancer is a wide-spread threat to the women's health. The drawbacks of conventional treatments necessitate the development of alternative strategies, where gene therapy has regained hope in achieving an efficient eradication of aggressive tumors. Monocarboxylate transporter 4 (MCT4) plays pivotal roles in the growth and survival of various tumors, which offers a promising target for treatment. In the present study, pH-responsive lipid nanoparticles (LNPs) based on the ionizable lipid,1,2-dioleoyl-3-dimethylammonium propane (DODAP), were designed for the delivery of siRNA targeting MCT4 gene to the breast cancer cells. Following multiple steps of characterization and optimization, the anticancer activities of the LNPs were assessed against an aggressive breast cancer cell line, 4T1, in comparison with a normal cell line, LX-2. The selection of the helper phospholipid to be incorporated into the LNPs had a dramatic impact on their gene delivery performance. The optimized LNPs enabled a powerful MCT4 silencing by ∼90 % at low siRNA concentrations, with a subsequent ∼80 % cytotoxicity to 4T1 cells. Meanwhile, the LNPs demonstrated a 5-fold higher affinity to the breast cancer cells versus the normal cells, in which they had a minimum effect. Moreover, the MCT4 knockdown by the treatment remodeled the cytokine profile in 4T1 cells, as evidenced by 90 % and ∼64 % reduction in the levels of TNF-α and IL-6; respectively. The findings of this study are promising for potential clinical applications. Furthermore, the simple and scalable delivery vector developed herein can serve as a breast cancer-targeting platform for the delivery of other RNA therapeutics.

Development of oral formulation of Lepidium seeds significantly decreases the high blood glucose levels in diabetic rats: in vitro formulation and in vivo antidiabetic performance.

BACKGROUND: Lepidium sativum, Garden Cress (GC), seeds have a lot of natural molecules with a pronounced activity against different disorders. It was reported that GC seeds have the ability to lower the blood glucose level. AIM: The aim of this work was to formulate GC seeds into oral tablets containing a fixed dose of the grounded seeds. Furthermore, the anti-diabetic performance of the prepared tablets was studied in the streptozotocin rats' model in comparison with positive control metformin. METHODS: Micrometrics of GC grounded seeds with different excipients were investigated. Then, GC tablets were prepared via direct compression technique. GC tablets were characterized for their uniformity of dosage unit, friability, hardness, disintegration time, and in vitro release. The antidiabetic effect was studied in rats for a period of 28 days. Glycosylated hemoglobin, liver performance, and lipid levels include total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also estimated. In addition, histopathological study of liver and pancreas was also performed. RESULTS: Prosolv®EasyTab produced tablets with higher hardness, lower disintegration time, and fast release. GC tablets significantly lower the elevated blood glucose level. In addition, they have antihyperlipidemic activity, hepatocellular protective role and restore the histology of the liver and pancreas. CONCLUSION: GC tablets could be a promising alternative formulation to control the high blood glucose level in diabetic rats rather than chemically derivatized drugs.

Synthesis and characterization of magnetic Ag-Fe3O4@polymer hybrid nanocomposite systems with promising antibacterial application.

INTRODUCTION: Bacterial infections caused by different strains of bacteria still one of the most important disorders affecting humans worldwide. Polymers nanocomposite systems could be considered as an alternative to conventional antibiotics to eradicate bacterial infections. SIGNIFICANCE: In an attempt to enhance the antibacterial performance of silver and iron oxide nanoparticles, decrease their aggregation and toxicity, a polymeric hybrid nanocomposite system combining both nanoparticles is produced. METHODS: Magnetic Ag-Fe3O4@polymer hybrid nanocomposites prepared using different polymers, namely polyethylene glycol 4000, ethyl cellulose, and chitosan were synthesized via wet impregnation and ball-milling techniques. The produced nanocomposites were tested for their physical properties and antibacterial activities. RESULTS: XRD, FT-IR, VSM, and TEM results confirmed the successful preparation of hybrid nanocomposites. Hybrid nanocomposites have average crystallite sizes in the following order Ag-Fe3O4@CS (8.9 nm) < Ag-Fe3O4@EC (9.0 nm) < Ag-Fe3O4@PEG4000 (9.4 nm) and active surface area of this trend Ag-Fe3O4@CS (130.4 m2g-1) > Ag-Fe3O4@EC (128.9 m2g-1) > Ag-Fe3O4@PEG4000 (123.4 m2g-1). In addition, they have a saturation magnetization in this order: Ag-Fe3O4@PEG4000 (44.82 emu/g) > Ag-Fe3O4@EC (40.14 emu/g) > Ag-Fe3O4@CS (22.90 emu/g). Hybrid nanocomposites have a pronounced antibacterial action against Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus intermedius compared to iron oxide nanoparticles and positive antibacterial drug. In addition, both Ag-Fe3O4@EC and Ag-Fe3O4@CS have a lower MIC values compared to Ag-Fe3O4@PEG and positive control. CONCLUSION: Magnetic Ag-Fe3O4 hybrid nanocomposites could be promising antibacterial nanomaterials and could pave the way for the development of new materials with even more unique properties and applications.

Non-coding RNA-directed therapeutics in lung cancer: Delivery technologies and clinical applications.

Lung cancer is one of the most aggressive and deadliest health threats. There has been an increasing interest in non-coding RNA (ncRNA) recently, especially in the areas of carcinogenesis and tumour progression. However, ncRNA-directed therapies are still encountering obstacles on their way to the clinic. In the present article, we provide an overview on the potential of targeting ncRNA in the treatment of lung cancer. Then, we discuss the delivery challenges and recent approaches enabling the delivery of ncRNA-directed therapies to the lung cancer cells, where we illuminate some advanced technologies including chemically-modified oligonucleotides, nuclear targeting, and three-dimensional in vitro models. Furthermore, advanced non-viral delivery systems recruiting nanoparticles, biomimetic delivery systems, and extracellular vesicles are also highlighted. Lastly, the challenges limiting the clinical trials on the therapeutic targeting of ncRNAs in lung cancer and future directions to tackle them are explored.

Impact of the functional coating of silver nanoparticles on their in vivo performance and biosafety.

OBJECTIVE AND SIGNIFICANCE: Silver nanoparticles (AgNPs) have become an interesting therapeutic modality and drug delivery platform. Herein, we aimed to investigate the impact of functional coating on the in vivo performance of AgNPs as an economic and scalable method to modulate their behavior. METHODS: AgNPs were coated with chitosan (CHI) as a model biopolymer using a one-pot reduction-based method, where CHI of two molecular weight ranges were investigated. The resultant CHI-coated AgNPs (AgNPs-CHI) were characterized using UV-VIS spectroscopy, DLS, and TEM. AgNPs were administered intravenously to rats and their biodistribution and serum levels of hepato-renal function markers were monitored 24 h later compared to plain AgNO3 as a positive control. RESULTS: UV-VIS spectroscopy confirmed the successful coating of AgNPs with CHI. DLS revealed the superiority of medium molecular weight CHI over its low molecular weight counterpart. AgNPs-CHI demonstrated a semi-complete clearance from the systemic circulation, a liver-dominated tissue tropism, and limited renal exposure. On the other hand, AgNO3 was poorly cleared from the circulation, with relatively high renal exposure and a non-specific tissue tropism. AgNPs-CHI were well-tolerated by the liver and kidney without signs of toxicity or inflammation, in contrary with AgNO3 which resulted in a significant elevation of Creatinine (CRE), Urea, and Total Protein (TP), suggesting a significant nephrotoxicity and inflammation. CONCLUSIONS: Functional coating of AgNPs with CHI substantially modulated their in vivo behavior, promoting their hepatic selectivity and biotolerability, which can be invested in the development of drug delivery systems for the treatment of liver diseases.

Lipid nanoparticles technology in vaccines: Shaping the future of prophylactic medicine.

Throughout decades, the intrinsic power of the immune system to fight pathogens has inspired researchers to develop techniques that enable the prevention or treatment of infections via boosting the immune response against the target pathogens, which has led to the evolution of vaccines. The recruitment of Lipid nanoparticles (LNPs) as either vaccine delivery platforms or immunogenic modalities has witnessed a breakthrough recently, which has been crowned with the development of effective LNPs-based vaccines against COVID-19. In the current article, we discuss some principles of such a technology, with a special focus on the technical aspects from a translational perspective. Representative examples of LNPs-based vaccines against cancer, COVID-19, as well as other infectious diseases, autoimmune diseases, and allergies are highlighted, considering the challenges and promises. Lastly, the key features that can improve the clinical translation of this area of endeavor are inspired.

Silver Nanoparticles Stabilized by Poly (Vinyl Pyrrolidone) with Potential Anticancer Activity towards Prostate Cancer.

Tumor necrosis factor (TNF-α) and inflammatory cytokine (IL-6) play a vital role in various cellular incidents such as the proliferation and death of cells during carcinogenesis. Hence, regulation of these biomarkers could be a promising tool for controlling tumor progression using nanoformulations. Silver nanoparticles-poly (vinyl pyrrolidone) (AgNPs-PVP) were prepared using the reduction of silver nitrate and stabilized with PVP. They are characterized through yield percentage, UV-VIS, FT-IR, size, charge, and morphology. The obtained AgNPs were tested for anticancer activity against prostate cancer (PC 3) and human skin fibroblast (HFS) cell lines. Moreover, biomarker-based confirmations like TNF-α and IL-6 were estimated. The synthesized AgNPs-PVP were stable, spherical in shape, with particle sizes of 122.33 ± 17.61 nm, a polydispersity index of 0.49 ± 0.07, and a negative surface charge of -19.23 ± 0.61 mV. In vitro cytotoxicity testing showed the AgNPs-PVP exhibited antiproliferation properties in PC3 in a dose-dependent manner. In addition, when compared to control cells, AgNPs-PVP has lower TNF-α with a significant value ( ∗ p < 0.05); the value reached 16.84 ± 0.71 pg/ml versus 20.81 ± 0.44 pg/ml, respectively. In addition, HSF cells showed a high level of reduction ( ∗∗∗ p < 0.001) in IL-6 production. This study suggested that AgNPs-PVP could be a possible therapeutic agent for human prostate cancer and anti-IL-6 in cancerous and noncancerous cells. Further studies will be performed to investigate the effect of AgNPs-PVP in different types of cancer.

Retardation of Bacterial Biofilm Formation by Coating Urinary Catheters with Metal Nanoparticle-Stabilized Polymers.

Urinary catheter infections remain an issue for many patients and can complicate their health status, especially for individuals who require long-term catheterization. Catheters can be colonized by biofilm-forming bacteria resistant to the administered antibiotics. Therefore, this study aimed to investigate the efficacy of silver nanoparticles (AgNPs) stabilized with different polymeric materials generated via a one-step simple coating technique for their ability to inhibit biofilm formation on urinary catheters. AgNPs were prepared and characterized to confirm their formation and determine their size, charge, morphology, and physical stability. Screening of the antimicrobial activity of nanoparticle formulations and determining minimal inhibitory concentration (MIC) and their cytotoxicity against PC3 cells were performed. Moreover, the antibiofilm activity and efficacy of the AgNPs coated on the urinary catheters under static and flowing conditions were examined against a clinical isolate of Escherichia coli. The results showed that the investigated polymers could form physically stable AgNPs, especially those prepared using polyvinyl pyrrolidone (PVP) and ethyl cellulose (EC). Preliminary screening and MIC determinations suggested that the AgNPs-EC and AgNPs-PVP had superior antibacterial effects against E. coli. AgNPs-EC and AgNPs-PVP inhibited biofilm formation to 58.2% and 50.8% compared with AgNPs-PEG, silver nitrate solution and control samples. In addition, coating urinary catheters with AgNPs-EC and AgNPs-PVP at concentrations lower than the determined IC50 values significantly (p < 0.05; t-test) inhibited bacterial biofilm formation compared with noncoated catheters under both static and static and flowing conditions using two different types of commercial Foley urinary catheters. The data obtained in this study provide evidence that AgNP-coated EC and PVP could be useful as potential antibacterial and antibiofilm catheter coating agents to prevent the development of urinary tract infections caused by E. coli.

Insight into the Inclusion Complexation of Fluconazole with Sulfonatocalix[4]naphthalene in Aqueous Solution, Solid-State, and Its Antimycotic Activity.

The study aims to assess the interaction between fluconazole and sulfonatocalix[4]naphthalene towards enhancing its dissolution performance and antimycotic activity. A solubility study was carried out at different pH conditions, and the results revealed the formation of a 1:1 molar ratio fluconazole-sulfonatocalix[4]naphthalene inclusion complex with an AL type phase solubility diagrams. The solid powder systems of fluconazole-sulfonatocalix[4]naphthalene were prepared using kneaded and co-evaporation techniques and physical mixtures. DCS, PXRD, TGA-DTG, FT-IR, and in vitro dissolution performance characterize the prepared systems. According to physicochemical characterization, the co-evaporation approach produces an amorphous inclusion complex of the drug inside the cavity of sulfonatocalix[4]naphthalene. The co-evaporate product significantly increased the drug dissolution rate up to 93 ± 1.77% within 10 min, unlike other prepared solid powders. The antimycotic activity showed an increase substantially (p ≤ 0.05, t-test) antimycotic activity of fluconazole co-evaporate mixture with sulfonatocalix[4]naphthalene compared with fluconazole alone against clinical strains of Candida albicans and Candida glabrata. In conclusion, sulfonatocalix[4]naphthalene could be considered an efficient complexing agent for fluconazole to enhance its aqueous solubility, dissolution performance, and antimycotic activity.

Biomedical Applications of Quantum Dots: Overview, Challenges, and Clinical Potential.

Despite the massive advancements in the nanomedicines and their associated research, their translation into clinically-applicable products is still below promises. The latter fact necessitates an in-depth evaluation of the current nanomedicines from a clinical perspective to cope with the challenges hampering their clinical potential. Quantum dots (QDs) are semiconductors-based nanomaterials with numerous biomedical applications such as drug delivery, live imaging, and medical diagnosis, in addition to other applications beyond medicine such as in solar cells. Nevertheless, the power of QDs is still underestimated in clinics. In the current article, we review the status of QDs in literature, their preparation, characterization, and biomedical applications. In addition, the market status and the ongoing clinical trials recruiting QDs are highlighted, with a special focus on the challenges limiting the clinical translation of QDs. Moreover, QDs are technically compared to other commercially-available substitutes. Eventually, we inspire the technical aspects that should be considered to improve the clinical fate of QDs.

Clinical translation of nanomedicines: Challenges, opportunities, and keys.

Despite the massive interest and recent developments in the field of nanomedicine, only a limited number of formulations have found their way to the clinics. This shortcoming reveals the challenges facing the clinical translation of this technology. In the current article, we summarize and evaluate the status, market situation, and clinical profiles of the reported nanomedicines, the shortcomings limiting their clinical translation, as well as some approaches designed to break through this barrier. Moreover, some emerging technologies that have the potential to compete with nanomedicines are highlighted. Lastly, we identify the key factors that should be considered in nanomedicine-related research to be clinically-translatable. These can be classified into five areas: rational design during the research and development stage, the recruitment of representative preclinical models, careful design of clinical trials, development of specific and uniform regulatory protocols, and calls for non-classic sponsorship. This new field of endeavor was firmly established during the last two decades and more in-depth progress is expected in the coming years.

Transethosomal Gel for the Topical Delivery of Celecoxib: Formulation and Estimation of Skin Cancer Progression.

The topical delivery of therapeutics is a promising strategy for managing skin conditions. Cyclooxygenase-2 (COX-2) inhibitors showed a possible target for chemoprevention and cancer management. Celecoxib (CXB) is a selective COX-2 inhibitor that impedes cell growth and generates apoptosis in different cell tumors. Herein, an investigation proceeded to explore the usefulness of nano lipid vesicles (transethosomes) (TES) of CXB to permit penetration of considerable quantities of the drug for curing skin cancer. The prepared nanovesicles were distinguished for drug encapsulation efficiency, vesicle size, PDI, surface charge, and morphology. In addition, FT-IR and DSC analyses were also conducted to examine the influence of vesicle components. The optimized formulation was dispersed in various hydrogel bases. Furthermore, in vitro CXB release and ex vivo permeability studies were evaluated. A cytotoxicity study proceeded using A431 and BJ1 cell lines. The expression alteration of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and DNA damage and fragmentation using qRT-PCR and comet assays were also investigated. Optimized CXB-TES formulation was spherically shaped and displayed a vesicle size of 75.9 ± 11.4 nm, a surface charge of -44.7 ± 1.52 mV, and an entrapment efficiency of 88.8 ± 7.2%. The formulated TES-based hydrogel displayed a sustained in vitro CXB release pattern for 24 h with an enhanced flux and permeation across rat skin compared with the control (free drug-loaded hydrogel). Interestingly, CXB-TES hydrogel has a lower cytotoxic effect on normal skin cells compared with TES suspension and CXB powder. Moreover, the level of expression of the CDKN2A gene was significantly (p ≤ 0.01, ANOVA/Tukey) decreased in skin tumor cell lines compared with normal skin cell lines, indicating that TES are the suitable carrier for topical delivery of CXB to the cancer cells suppressing their progression. In addition, apoptosis demonstrated by comet and DNA fragmentation assays was evident in skin cancer cells exposed to CXB-loaded TES hydrogel formulation. In conclusion, our results illustrate that CXB-TES-loaded hydrogel could be considered a promising carrier and effective chemotherapeutic agent for the management of skin carcinoma.

Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance.

The interaction between meloxicam and sulfonatocalix [4] naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix [4] naphthalene. The solubility phase diagram was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix [4] naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release (p ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR10 in the investigated media, with average values ranging from 5.4-65.28 folds and 7.3-90.7, respectively. In conclusion, sulfonatocalix [4] naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.

Silver Nanoparticle-Coated Ethyl Cellulose Inhibits Tumor Necrosis Factor-α of Breast Cancer Cells.

INTRODUCTION: Cancer is one of the leading causes of death worldwide. In many cases, cancer is related to the elevated expression of a significant cytokine known as tumor necrosis factor-α (TNF-α). Breast cancer in particular is linked to increased proliferation of tumor cells, high incidence of malignancies, more metastases, and generally poor prognosis for the patient. The research sought to assess the effect of silver nanoparticles reduced with ethyl cellulose polymer (AgNPs-EC) on TNF-α expression in MCF-7 human breast cancer cells. METHODS: The AgNPs-EC were produced using the green synthesis reduction method, and their formation was proofed via UV-VIS spectroscopy. Furthermore, AgNPs-EC were characterized for their size, charge, morphology, Ag ion release, and stability. The MCF-7 cells were treated with AgNPs-EC. Then, the expression of TNF-α genes was determined through PCR in real time, and protein expression was studied using ELISA. RESULTS: The AgNPs-EC were spherical with an average size of 150±5.1 nm and a zeta-potential of -41.4±0.98 mV. AgNPs-EC had an inhibitory effect on cytokine mRNA and protein expression levels, which suggests that they could be used safely in the fight against cancer. AgNPs-EC cytotoxicity was also found to be non-toxic to MCF-7. CONCLUSION: Our data determined AgNPs-EC as a novel inhibitor of TNF-α production. These results are promising for developing novel therapeutic approaches for the future treatment of cancer with safe materials.

In Vitro Characterization of Inhalable Cationic Hybrid Nanoparticles as Potential Vaccine Carriers.

In this study, PGA-co-PDL nanoparticles (NPs) encapsulating model antigen, bovine serum albumin (BSA), were prepared via double emulsion solvent evaporation. In addition, chitosan hydrochloride (CHL) was incorporated into the external phase of the emulsion solvent method, which resulted in surface adsorption onto the NPs to form hybrid cationic CHL NPs. The BSA encapsulated CHL NPs were encompassed into nanocomposite microcarriers (NCMPs) composed of l-leucine to produce CHL NPs/NCMPs via spray drying. The CHL NPs/NCMPs were investigated for in vitro aerosolization, release study, cell viability and uptake, and stability of protein structure. Hybrid cationic CHL NPs (CHL: 10 mg/mL) of particle size (480.2 ± 32.2 nm), charge (+14.2 ± 0.72 mV), and BSA loading (7.28 ± 1.3 µg/mg) were produced. The adsorption pattern was determined to follow the Freundlich model. Aerosolization of CHL NPs/NCMPs indicated fine particle fraction (FPF: 46.79 ± 11.21%) and mass median aerodynamic diameter (MMAD: 1.49 ± 0.29 µm). The BSA α-helical structure was maintained, after release from the CHL NPs/NCMPs, as indicated by circular dichroism. Furthermore, dendritic cells (DCs) and A549 cells showed good viability (≥70% at 2.5 mg/mL after 4-24 h exposure, respectively). Confocal microscopy and flow cytometry data showed hybrid cationic CHL NPs were successfully taken up by DCs within 1 h of incubation. The upregulation of CD40, CD86, and MHC-II cell surface markers indicated that the DCs were successfully activated by the hybrid cationic CHL NPs. These results suggest that the CHL NPs/NCMPs technology platform could potentially be used for the delivery of proteins to the lungs for immunostimulatory applications such as vaccines.

Recent updates in COVID-19 with emphasis on inhalation therapeutics: Nanostructured and targeting systems.

The current world health threat posed by the novel coronavirus disease of 2019 (COVID-19) calls for the urgent development of effective therapeutic options. COVID-19 needs daunting routes such as nano-antivirals. Hence, the role of nanotechnology is very critical in combating this nano-enemy "virus." Although substantial resources are under ongoing attention for prevention and care, we would like to start sharing with readers our vision of the role of inhaled nanomaterials and targeting systems that can play an important role in the fight against the COVID-19. In this review, we underline the genomic structure of COVID-19, recent modes of virus transmission with measures to control the infection, pathogenesis, clinical presentation of SARS-CoV-2, and how much the virus affects the lung. Additionally, the recent therapeutic approaches for managing COVID-19 with emphasis on the value of nanomaterial-based technical approaches are discussed in this review. This review also focuses on the safe and efficient delivery of useable targeted therapies using designed nanocarriers. Moreover, the effectiveness and availability of active targeting of certain specific receptors expressed on the coronavirus surfaces via tailored ligand nanoparticles are manipulated. It was also highlighted in this review the role of inhaled medicines including antivirals and repurposed drugs for fighting the associated lung disorders and efficiency of developed vaccines. Moreover, the inhalation delivery safety techniques were also highlighted.

Different cellulosic polymers for synthesizing silver nanoparticles with antioxidant and antibacterial activities.

The use of cellulosic polymers as efficient reducing, coating agents, and stabilizers in the formulation of silver nanoparticles (AgNPs) with antioxidant and antibacterial activity was investigated. AgNPs were synthesized using different cellulosic polymers, polyethylene glycol, and without polymers using tri-sodium citrate, for comparison. The yield, morphology, size, charge, in vitro release of silver ion, and physical stability of the resulting AgNPs were evaluated. Their antioxidant activity was measured as a scavenging percentage compared with ascorbic acid, while their antibacterial activity was evaluated against different strains of bacteria. The amount of AgNPs inside bacterial cells was quantified using an ICP-OES spectrometer, and morphological examination of the bacteria was performed after AgNPs internalization. Cellulosic polymers generated physically stable AgNPs without any aggregation, which remained physically stable for 3 months at 25.0 ± 0.5 and 4.0 ± 0.5 °C. AgNPs formulated using ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) had significant (p ≤ 0.05; ANOVA/Tukey) antibacterial activities and lower values of MIC compared to methylcellulose (MC), PEG, and AgNPs without a polymeric stabilizer. Significantly (p ≤ 0.05; ANOVA/Tukey) more AgNPs-EC and AgNPs-HPMC were internalized in Escherichia coli cells compared to other formulations. Thus, cellulosic polymers show promise as polymers for the formulation of AgNPs with antioxidant and antibacterial activities.

Fluorescent Nanoparticles Coated with a Somatostatin Analogue Target Blood Monocyte for Efficient Leukaemia Treatment.

BACKGROUND: Leukaemia is the most prevalent form of cancer-causing death in a large number of populations and needs prompt and effective treatment. Chemotherapeutics can be used to treat leukaemia, but their pronounced killing effects to other living cells is still an issue. Active targeting to certain specific receptors in leukaemic cells is the best way to avoid damage to other living cells. Leukaemic cells can be targeted using novel nanoparticles (NPs) coated with a specific ligand, such as octreotide (OCD), to target somatostatin receptor type 2 (SSTR2), which is expressed in leukaemic cells. METHODS: Amino-PEGylated quantum dots (QDs) were chosen as model NPs. The QDs were first succinylated using succinic anhydride and then coated with OCD. The reactivity and selectivity of the formulated QDs-OCD were studied in cell lines with well-expressed SSTR2, while fluorescence was detected using confocal laser scanning microscopy (CLSM) and flow cytometry (FACS). Conclusively, QD-OCD targeting to blood cells was studied in vivo in mice and detected using inductively coupled plasma mass spectrometry and CLSM in tissues. RESULTS: Highly stable QDs coated with OCD were prepared. FACS and CLSM showed highly definite interactions with overexpressed SSTR2 in the investigated cell lines. Moreover, the in vivo results revealed a higher concentration of QDs-OCD in blood cells. The fluorescence intensity of the QDs-OCD was highly accumulated in blood cells, while the unmodified QDs did not accumulate significantly in blood cells. CONCLUSION: The formulated novel QDs-OCD can target SSTR2 overexpressed in blood cells with great potential for treating blood cancer.

Antibacterial nanotruffles for treatment of intracellular bacterial infection.

Bacterial pathogens residing in host macrophages in intracellular infections are hard to eradicate because traditional antibiotics do not readily enter the cells or get eliminated via efflux pumps. To overcome this challenge, we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded with two antibacterial agents - pexiganan and silver (Ag) nanoparticles. Here, pexiganan was loaded in 600 nm poly(lactic-co-glycolic acid) (PLGA) particles (NP), and the particle surface was modified with an iron-tannic acid supramolecular complex (pTA) that help attach Ag nanoparticles. PLGA particles coated with Ag (NP-pTA-Ag) were taken up by macrophages, but not by non-phagocytic cells, such as fibroblasts, reducing non-specific toxicity associated with Ag nanoparticles. NP-pTA-Ag loaded with pexiganan (Pex@NP-pTA-Ag) showed more potent antibacterial activity against various intracellular pathogens than NP-pTA-Ag or Pex@NP (pexiganan-loaded NP with no Ag), suggesting a collaborative function between pexiganan and Ag nanoparticles. Mouse whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising strategy for the treatment of intracellular bacterial infection.

Effect of Spray Drying on Amorphization of Indomethacin Nicotinamide Cocrystals; Optimization, Characterization, and Stability Study.

Cocrystals have gained a lot of consideration regarding its superior role in enhancement of solubility and dissolution of the included API. Cocrystals could be converted to coamorphous systems via different techniques like milling and quench cooling; however, the use of spray-drying technique has not been investigated before. So, the aim of this study was to explore the effect of spray drying on the amorphization of indomethacin/nicotinamide, INDNIC, as model cocrystals. Spray-drying operating parameters were optimized using the Taguchi design of experiment for maximum powder yield and low moisture content. The obtained INDNIC spray-dried cocrystals were characterized for their degree of crystallinity, morphology, moisture content, and dissolution performance. In addition, stability study was performed at different temperature and humidity conditions. Experimental design results delineate that spray-drying inlet temperature and cocrystal concentrations as the most influential factors for maximum powder yield and low moisture content. Powder X-ray diffraction and differential scanning calorimetry studies revealed the conversion of INDNIC cocrystals to a partial coamorphous or coamorphous structure without dissociation of INDNIC molecular structure. INDNIC coamorphous powders showed a significantly higher release of IND compared with cocrystals and remain physically stable for 2 months when stored in the refrigerator.