Enhanced intracellular accumulation and cytotoxicity of bortezomib against liver cancer cells using N-stearyl lactobionamide surface modified solid lipid nanoparticles.

Asialoglycoprotein receptors (ASGPRs) are highly expressed on hepatocytes and have been used for liver-targeted delivery and hepatocellular carcinoma (HCC) therapy. However, targeted delivery of bortezomib (BTZ) to HCC has not been reported. In this study, N-stearyl lactobionamide (N-SALB) with galactose (Gal) moiety was synthesized as a targeting agent and its structure was confirmed by FT-IR and NMR analyses. N-SALB surface-modified solid lipid nanoparticles (SLNs) loaded with BTZ (Gal-SLNs/BTZ) were developed to target BTZ delivery into HCC cancer cells. The Gal-SLNs/BTZ had an average particle size of 116.3 nm, polydispersity index (PDI) of 0.210, and zeta potential of -13.8 mV. TEM analysis showed their nanometer-sized spherical morphology. The encapsulation efficiency (EE) and drug loading (DL) capacity were 84.5 % and 1.16 %, respectively. Release studies showed that BTZ loaded inside the SLNs was slowly released over a period of 72 h at pH 7.4. Flow cytometry analysis showed significantly higher intracellular uptake of N-SALB-targeted nanoparticles than non-targeted nanoparticles in HepG2 cells. All lipid formulations showed good biocompatibility in the cytotoxicity study using MTT assay. Concentration-dependent cytotoxicity was observed for all formulations, with N-SALB-targeted nanoparticles demonstrating more cytotoxicity against HepG2 cells. The highest percentage of apoptosis was obtained for N-SALB-targeted nanoparticles compared to non-targeted nanoparticles (42.2 % and 8.70 %, respectively). Finally, biodistribution studies in HepG2 bearing nude mice showed that the accumulation of targeted nanoparticles in the tumor was significantly higher than non-targeted nanoparticles.

RNA aptamer-mediated gene therapy of prostate cancer: lessons from the past and future directions.

INTRODUCTION: Prostate cancer (PCa) is one of the most prevalent cancers in the world, and the fifth cause of death from cancer in men. Among the non-surgical treatments for PCa, gene therapy strategies are in the early stages of development and recent clinical trials have provided new insights suggesting promising future. AREAS COVERED: Recently, the creation of targeted gene delivery systems, based on specific PCa cell surface markers, has been viewed as a viable therapeutic approach. Prostate-specific membrane antigen (PSMA) is vastly expressed in nearly all prostate malignancies, and the intensity of expression increases with tumor aggressiveness, androgen independence, and metastasis. RNA aptamers are short and single-stranded oligonucleotides, which selectively bind to a specific ligand on the surface of the cells, which makes them fascinating small molecules for target delivery of therapeutics. PSMA-selective RNA aptamers represent great potential for developing targeted-gene delivery tools for PCa. EXPERT OPINION: This review provides a thorough horizon for the researchers interested in developing targeted gene delivery systems for PCa via PSMA RNA aptamers. In addition, we provided general information about different prospects of RNA aptamers including discovery approaches, stability, safety, and pharmacokinetics.

Ciprofloxacin antibiotic removal from aqueous solutions by ZnO nanoparticles coated on ACA: modeling and optimization.

Antibiotics are one of the most widely used drug groups. The presence of antibiotics in urban water sources and sewage creates many environmental and medical risks for humans and other living organisms. In this study, the potential of zinc oxide (ZnO) coated on almond shell activated carbon (ACA-ZnO) in removing ciprofloxacin (CIP) from aqueous solutions was investigated. Almond shell was used to make activated carbon. Zinc oxide nanoparticles were prepared by the sol-gel method, and finally, ZnO nanoparticles were bonded to activated carbon. The effect of independent parameters pH, contact time, adsorbent dose, and initial CIP concentration on CIP removal efficiency using ACA-ZnO was investigated by response surface methodology. Optimal removal was obtained at pH = 5.4, CIP initial concentration = 7.4 mg/L, adsorbent dose = 0.82 g/L, and reaction time = 67.3 min. This study followed a quadratic model (R2 = 0.958). The best model of adsorption isotherm fits with the Freundlich model (R2 = 0.9972) and the maximum capacity was 251.42 mg/g adsorption kinetics, and pseudo-second-order kinetic model (R2 = 0.959). The results of this study showed that ACA-ZnO as an adsorbent is very efficient, without environmental side effect and cost-benefit.

Statistical modeling and optimization of dexamethasone adsorption from aqueous solution by Fe3O4@NH2-MIL88B nanorods: Isotherm, Kinetics, and Thermodynamic.

The presence of pharmaceutical compounds in the environment poses a significant threat to human and aquatic animal health. Dexamethasone (DEX), a synthetic steroid hormone with endocrine-disrupting effects, is one such compound that needs to be effectively removed before discharging into the environment. This research presents a novel approach utilizing magnetically recyclable Fe3O4@NH2-MIL88B NRs as an efficient adsorbent for the treatment of DEX from aqueous solutions. The synthesized adsorbent was characterized by X-ray diffraction (XRD), scanning microscopy (SEM), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), diffuse reflectance spectra (DRS), and Fourier transform infrared spectroscopy (FTIR). Response surface methodology based on central composite design (RSM-CCD) was employed to optimize DEX removal efficiency by determining the optimal conditions, including pH, adsorbent dose, time, and DEX concentration. Under the optimized conditions (pH: 5.53, adsorbent dose: 0.185 g/L, time: 16.068 min, and DEX concentration: 33.491 mg/L), Fe3O4@NH2-MIL88B NRs revealed remarkable DEX adsorption efficiency of 91 ± 1.34% and adsorption capacity of 180.01 mg/g. The Langmuir isotherm and pseudo-second-order kinetic model were found to fit well with the experimental data, indicating a monolayer and chemical adsorption process. Thermodynamic analysis revealed that the adsorption process was spontaneous and endothermic. The study also investigated the inhibitory effect of background ions on DEX removal by Fe3O4@NH2-MIL88B NRs. Magnesium exhibited superior competitive ability with dexamethasone to occupy the active sites of the adsorbent compared to other background ions. The reuse of the adsorbent over ten consecutive cycles resulted in a 39.46% decrease in removal efficiency. The Fe3O4@NH2-MIL88B NRs are surrounded by abundant amounts of functional groups and π-electrons bands that can play a key role in the adsorption and separation of DEX from aqueous environments. The promising results obtained under real conditions highlight the potential of Fe3O4@NH2-MIL88B NRs as a practical and efficient adsorbent for the removal of DEX and other similar corticosteroids from aqueous solutions.

Intratumoural Delivery of mRNA Loaded on a Cationic Hyper-Branched Cyclodextrin-Based Polymer Induced an Anti-Tumour Immunological Response in Melanoma.

mRNA technology has demonstrated potential for use as an effective cancer immunotherapy. However, inefficient in vivo mRNA delivery and the requirements for immune co-stimulation present major hurdles to achieving anti-tumour therapeutic efficacy. Therefore, we used a cationic hyper-branched cyclodextrin-based polymer to increase mRNA delivery in both in vitro and in vivo melanoma cancer. We found that the transfection efficacy of the mRNA-EGFP-loaded Ppoly system was significantly higher than that of lipofectamine and free mRNA in both 2D and 3D melanoma cancer cells; also, this delivery system did not show cytotoxicity. In addition, the biodistribution results revealed time-dependent and significantly higher mEGFP expression in complexes with Ppoly compared to free mRNA. We then checked the anti-tumour effect of intratumourally injected free mRNA-OVA, a foreign antigen, and loaded Ppoly; the results showed a considerable decrease in both tumour size and weight in the group treated with OVA-mRNA in loaded Ppoly compared to other formulations with an efficient adaptive immune response by dramatically increasing most leukocyte subtypes and OVA-specific CD8+ T cells in both the spleen and tumour tissues. Collectively, our findings suggest that the local delivery of cationic cyclodextrin-based polymer complexes containing foreign mRNA antigens might be a good and reliable concept for cancer immunotherapy.

Oral supplementation of solvent-free kynurenic acid/cyclodextrin nanosponges complexes increased its bioavailability.

Many nutraceuticals present problems due to their poor water solubility or stability, which prevents the final bioactivity achievement. For that reason, the oral administration of KYNA complexed with HPß-CD and ßNS-CDI nanosponges was evaluated in mice. The solvent-free technology was used to prepare the complexes in a complete comparison between kneading in ball milling and classical inclusion complex preparation. The solvent-free ones showed higher strength and efficiency with ball milling, considerably reducing time. A 50 mg KYNA/kg/day dosage was orally administered in formulations showing a higher bioavailability when the nutraceutical was complexed with ßNS-CDI compared to HPß-CD and free KYNA, respectively. Several antioxidant statuses demonstrated a higher global antioxidant level perfectly related to bioavailability. Finally, the formulation of KYNA reduced the temporal oxidative stress damage in the kidney and liver, making ßNS-CDI the best formulation. These results suggest an important future application of cyclodextrin-based nanosponges for the oral delivery of nutraceuticals and their stabilization.

Hyper-Branched Cyclodextrin-Based Polymers as Anticoagulant Agents: In Vitro and In Vivo Studies.

This study tested the anticoagulant effect of cyclodextrin (CD) hyper-branched-based polymers (HBCD-Pols). These polymers were synthesized and tested for their coagulant characteristics in vitro and in vivo. Due to their polymeric structure and anionic nature, the polymers can chelate Ca2+, reducing the free quantity in blood. HBCD-Pol increased the blood clotting time, PT, and aPTT 3.5 times over the control, showing a better effect than even ethylenediaminetetraacetic acid (EDTA), as occured with recalcification time as well. A titration of HBCD-Pol and EDTA showed exciting differences in the ability to complex Ca2+ between both materials. Before executing in vivo studies, a hemocompatibility study was carried out with less than 5% red blood cell hemolysis. The fibrinogen consumption and bleeding time were analyzed in vivo. The fibrinogen was considerably decreased in the presence of HBCD-Pol in a higher grade than EDTA, while the bleeding time was longer with HBCD-Pols. The results demonstrate that the anticoagulant effect of this HBCD-Pol opens novel therapy possibilities due to the possible transport of drugs in this carrier. This would give combinatorial effects and a potential novel anticoagulant therapy with HBCD-Pol per se.

Hyper-Branched Cationic Cyclodextrin Polymers for Improving Plasmid Transfection in 2D and 3D Spheroid Cells.

In this article, we used monolayer two dimensional (2D) and 3D multicellular spheroid models to improve our understanding of the gene delivery process of a new modified cationic hyper-branched cyclodextrin-based polymer (Ppoly)-loaded plasmid encoding Enhanced Green Fluorescent Protein (EGFP). A comparison between the cytotoxicity effect and transfection efficiency of the plasmid DNA (pDNA)-loaded Ppoly system in 2D and 3D spheroid cells determined that the transfection efficiency and cytotoxicity of Ppoly-pDNA nanocomplexes were lower in 3D spheroids than in 2D monolayer cells. Furthermore, histopathology visualization of Ppoly-pDNA complex cellular uptake in 3D spheroids demonstrated that Ppoly penetrated into the inner layers. This study indicated that the Ppoly, as a non-viral gene delivery system in complex with pDNA, is hemocompatible, non-toxic, high in encapsulation efficiency, and has good transfection efficiency in both 2D and 3D cell cultures compared to free pDNA and lipofectamine (as the control).

Photocatalytic degradation of bisphenol a from aqueous solution using bismuth ferric magnetic nanoparticle: synthesis, characterization and response surface methodology-central composite design modeling.

Purpose: Bisphenol A (BPA), as endocrine-disrupting compound (EDC), is extensively used as an important chemical in the synthesis of polycarbonate polymers and epoxy resins. BPA absorption into the body can result in the development of metabolic disorders such as low sex-specific neurodevelopment, immune toxicity, neurotoxicity and interference of cellular pathway. Therefore, the presence of BPA in the body and the environment can create hazards that must reach standards before being discharged into the environment. Methods: In this study, bismuth ferric nanomagnetic (BFO NMPs) were successfully synthesized via sol-gel method and developed as photocatalysts for BPA removal under visible light irradiation. FE-SEM, TEM, PL, XRD, UV-Vis DRS, VSM, EDX, and FTIR were used to characterize the BFO NMPs. Results: RSM model (R2 = 0.9745) showed a good correlation between experimental and predicted removal efficiency of BPA. The investigation of four independent variables indicated that pH had the most significant positive effect on the degradation of BPA. Under optimal conditions (pH = 4.042, catalyst dose = 7.617 mg, contact time = 122.742 min and BPA concentration = 15.065 mg/L), maximum degradation was calculated to be 98.7%. After five recycles, the removal of BPA remained >82%, which indicated the proper ability to reuse the catalyst. Conclusion: In conclusion, it can be stated like BPA, the prepared BFO NMPs is a promising photocatalyst for practical application in organic pollutant decomposition.

Synthesis and preparation of vitamin A coupled butein-loaded solid lipid nanoparticles for liver fibrosis therapy in rats.

The development of a therapeutic system for hepatic fibrosis has become a research hotspot to date. Butein, a simple chalcone derivative, displays anti-fibrotic effects through different pathways. However, impurities, low solubility, and low concentration in the target tissue hinder therapy with herbal ingredients. Hepatic stellate cells (HSCs), the vitamin A (VA) storage cells, as the main contributors to liver fibrogenesis, are not readily accessible to drugs owing to their anatomical location. Targeted delivery of therapeutics to the activated HSCs is therefore critical for successful treatment. For these reasons, the current study aimed at increasing butein delivery to the liver. Hence, high purity butein was synthesized in three steps. A novel VA-Myrj52 ester conjugate was also synthesized using all-trans retinoic acid and a hydrophilic emulsifier (Myrj52) as a targeting agent. Next, butein was encapsulated inside the novel VA-modified solid lipid nanoparticles (VA-SLNs) and studied in vitro and in vivo. According to our evaluations, negatively charged SLNs with a mean diameter of 150 nm and entrapment efficacy of 75 % were successful in liver fibrosis amelioration. Intraperitoneal (i.p.) injection of VA-SLNs in fibrotic rats, for four weeks long, reduced serum AST and ALT by 58% (P, 0.001) and 72% (P, 0.05), respectively, concerning the CCl4 group. Additionally, histologic damage score decline and normalization of tissue oxidative stress markers collectively confirmed the efficacy of formulations in hepatic fibrosis and kidney damage amelioration.

Health impact assessment and evaluation of economic costs attributed to PM2.5 air pollution using BenMAP-CE.

Air pollution is considered the most prominent public health. Economically, air pollution imposes additional costs on governments. This study aimed to quantify health effects and associated economic values of reducing PM2.5 air pollution using BenMAP-CE in Qom in 2019. The air quality data were acquired from Qom Province Environmental Protection Agency, and the population data were collected from Qom Province Management and Planning Organization website. The number of deaths due to Stroke, Chronic Obstructive Pulmonary Disease, Lung Cancer, and Ischemic Heart Disease attributable to PM2.5 were estimated using BenMAP-CE based on two control scenarios, 2.4 and 10 µg/m3, known as scenarios I and II, respectively. The associated economic effect of premature deaths was assessed by value of a statistical life (VSL) approach. The annual average of PM2.5 concentration was found to be 16.32 µg/m3 (SD: 9.93). A total of 4694.5 and 2475.94 premature deaths in scenarios I and II were found to be attributable to PM2.5 in overall, respectively. The total associated cost was calculated to be 855.91 and 451.40 million USD in scenarios I and II, respectively. The total years of life lost due to PM2.5 exposure in 2019 was 158,657.06 and 78,351.51 in scenarios I and II, respectively. The results of both health and economic assessment indicate the importance of solving the air pollution problem in Qom, as well as other big cities in Iran. The elimination of limitations, such as insufficient local data, should be regarded in future studies.

The Therapeutic Benefits of Intravenously Administrated Nanoparticles in Stroke and Age-related Neurodegenerative Diseases.

The mean global lifetime risk of neurological disorders such as stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) has shown a large effect on economy and society. Researchers are still struggling to find effective drugs to treat neurological disorders and drug delivery through the blood-brain barrier (BBB) is a major challenge to be overcome. The BBB is a specialized multicellular barrier between peripheral blood circulation and neural tissue. Unique and selective features of the BBB allow it to tightly control brain homeostasis as well as the movement of ions and molecules. Failure in maintaining any of these substances causes BBB breakdown and subsequently enhances neuroinflammation and neurodegeneration. BBB disruption is evident in many neurological conditions. Nevertheless, the majority of currently available therapies have tremendous problems with drug delivery into the impaired brain. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem. NPs are colloidal systems with a size range of 1-1000 nm which can encapsulate therapeutic payloads, improve drug passage across the BBB, and target specific brain areas in neurodegenerative/ischemic diseases. A wide variety of NPs has been displayed for the efficient brain delivery of therapeutics via intravenous administration, especially when their surfaces are coated with targeting moieties. Here, we discuss recent advances in the development of NP-based therapeutics for the treatment of stroke, PD, and AD, as well as the factors affecting their efficacy after systemic administration.

Cyclodextrin-Based Nanosponges as Perse Antimicrobial Agents Increase the Activity of Natural Antimicrobial Peptide Nisin.

At present, antibiotic resistance is considered a real problem. Therefore, for decades scientists have been looking for novel strategies to treat bacterial infections. Nisin Z, an antimicrobial peptide (AMP), can be considered an option, but its usage is mainly limited by the poor stability and short duration of its antimicrobial activity. In this context, cyclodextrin (CD)-based nanosponges (NSs), synthesized using carbonyldiimidazole (CDI) and pyromellitic dianhydride (PMDA), were chosen for nisin Z loading. To determine the minimum inhibitory of nisin Z loaded on CD-NS formulations, agar well diffusion plates were used. Then, the bactericide concentrations of nisin Z loaded on CD-NS formulations were determined against Gram-positive (Staphylococcus aureus) and -negative (Escherichia coli) bacteria, using microdilution brain heart infusion (BHI) and tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The minimum and bactericide inhibitory values of the nisin complex with NSs were potentially decreased against both bacteria, compared with the nisin-free sample, while the nisin complex with ß-CD showed lower antibacterial activity. The antimicrobial effect was also demonstrated by free NSs. Furthermore, the total viable counts (TVCs) antibacterial experiment indicated that the combination of nisin Z in both PMDA and CDI ß-CD-based NSs, especially CDI, can provide a better conservative effect on cooked chicken meat. Generally, the present study outcomes suggest that the cross-linked ß-CD-based NSs can present their own antimicrobial potency or serve as promising carriers to deliver and enhance the antibacterial action of nisin Z.

Stabilization and Anticancer Enhancing Activity of the Peptide Nisin by Cyclodextrin-Based Nanosponges against Colon and Breast Cancer Cells.

The great variability of cancer types demands novel drugs with broad spectrum, this is the case of Nisin, a polycyclic antibacterial peptide that recently has been considered for prevention of cancer cells growth. As an accepted food additive, this drug would be very useful for intestinal cancers, but the peptide nature would make easier its degradation by digestion procedures. For that reason, the aim of present study to investigate the protective effect of two different ß-cyclodextrin-based nanosponges (carbonyl diimidazole and pyromellitic dianhydride) and their anti-cancer enhancement effect of Nisin-Z encapsulated with against colon cancer cells (HT-29). To extend its possible use, a comparison with breast (MCF-7) cancer cell was carried out. The physicochemical properties, loading efficiency, and release kinetics of Nisin complex with nanosponges were studied. Then, tricin-SDS-PAGE electrophoresis was used to understand the effect of NSs on stability of Nisin-Z in the presence of gastric peptidase pepsin. In addition, the cytotoxicity and cell membrane damage of Nisin Z were evaluated by using the MTT and LDH assay, which was complemented via Annexin-V/ Propidium Iodide (PI) by using flowcytometry. CD-NS are able to complex Nisin-Z with an encapsulation efficiency around 90%. A protective effect of Nisin-Z complexed with CD-NSs was observed in presence of pepsin. An increase in the percentage of apoptotic cells was observed when the cancer cells were exposed to Nisin Z complexed with nanosponges. Interestingly, Nisin Z free and loaded on PMDA/CDI-NSs is more selectively toxic towards HT-29 cells than MCF-7 cancer cells. These results indicated that nanosponges might be good candidates to protect peptides and deliver drugs against intestinal cancers.

Safety and Toxicity Issues of Therapeutically Used Nanoparticles from the Oral Route.

The emerging science of nanotechnology sparked a research attention in its potential benefits in comparison to the conventional materials used. Oral products prepared via nanoparticles (NPs) have garnered great interest worldwide. They are used commonly to incorporate nutrients and provide antimicrobial activity. Formulation into NPs can offer opportunities for targeted drug delivery, improve drug stability in the harsh environment of the gastrointestinal (GI) tract, increase drug solubility and bioavailability, and provide sustained release in the GI tract. However, some issues like the management of toxicity and safe handling of NPs are still debated and should be well concerned before their application in oral preparations. This article will help the reader to understand safety issues of NPs in oral drug delivery and provides some recommendations to the use of NPs in the drug industry.

The Factors Determining the Skin Penetration and Cellular Uptake of Nanocarriers: New Hope for Clinical Development.

The skin provides a protective barrier against toxic environments and also offers a valuable route for topical drug delivery. The stratum corneum (SC) is the outermost layer of the skin and serves as the major barrier to chemical transfer through the skin. The human skin barrier is particularly difficult to overcome because of the complex composition and structure of the SC. Nanoparticulate carriers have gained widespread attention in topical drug delivery due to their tunable and versatile properties. The present review summarizes the main factors involved in skin penetration of nanocarriers containing the drug. Employment of nanotechnology in topical delivery has grown progressively during recent years; however, it is important to monitor the skin penetration of nanocarriers prior to their use to avoid possible toxic effects. Nanocarriers can act as a means to increase skin permeation of drugs by supporting direct interaction with the SC and increasing the period of permanence on the skin. Skin penetration is influenced by the physicochemical characteristics of nanocarriers such as composition, size, shape, surface chemistry, as well as skin features. Considering that the target of topical systems based on nanocarriers is the penetration of therapeutic agents in the skin layers, so a detailed understanding of the factors influencing skin permeability of nanocarriers is essential for safe and efficient therapeutic applications.

Surface modification with cholesteryl acetyl carnitine, a novel cationic agent, elevates cancer cell uptake of the PEGylated liposomes.

The present study aimed to synthesize cholesteryl acetyl carnitine (CAC), and surface modify the PEGylated liposomes with the intention of enhanced cancer cell uptake. For this, CAC synthesis was performed in amine-free esterification conditions and then four liposomal formulations of unmodified, CAC/PEG, and CAC + PEG-modified were prepared by ethanol injection method. Cytotoxicity of the liposomes was investigated in A549 cells, followed by cellular uptake assessments of coumarin 6 (C6)-loaded liposomes. The results of ATR-FTIR, 1HNMR, and 13CNMR demonstrated successful formation of CAC. A molecular docking study showed efficient binding affinities rather than carnitine to the active site of four carnitine transporters. Liposomal formulations possessed spherical morphology with a mean particle size range of 112-138 nm, narrow size distribution, and negative surface charge. All formulations had low cytotoxicity at 0.5 mg/ml, but high cytotoxicity at around 2.5 mg/ml. The lowest IC50 was obtained for CAC modified liposomes. CAC + PEG-modified liposomes had the highest cellular uptake. In conclusion, CAC + PEG modification of liposomes is an effective approach for increasing A549 cellular uptake, with low cytotoxicity at commonly applied liposome concentrations. The elevated uptake may be due to the involvement of the organic cation transporter, cationic structure, and the metabolic preference of CAC in cancer cells.

Oral delivery of solid lipid nanoparticles: underlining the physicochemical characteristics and physiological condition affecting the lipolysis rate.

INTRODUCTION: Lipid-based nano-drug delivery systems (LBNDDSs) have gained widespread attention in oral drug delivery due to their tunable and versatile properties such as biocompatibility and biodegradability, which makes them promising delivery systems for a variety of therapeutics. Currently, different types of LBNDDSs including liposomes, micelles, nanoemulsions, and solid lipid nanoparticles (SLNs) are developed for drug delivery applications. SLNs can be used as a controlled drug delivery system for oral delivery applications. However, its lipidic context makes that susceptible to lipolysis. The lipolysis rate of SLNs is affected by many factors that raise many questions for developing a more efficient delivery system. AREAS COVERED: In the present work, we highlighted different factors affecting the digestion rate/level of SLNs in the gastrointestinal tract. This paper can be most useful for those researchers who are keen to develop a properly controlled drug delivery system based on SLNs for oral delivery applications. EXPERT OPINION: SLNs can be used as a controlled drug delivery system for oral delivery applications. However, its lipidic context makes that susceptible to lipolysis. The lipolysis rate of SLNs is affected by many factors that raise many questions for developing a more efficient delivery system.

Bortezomib-loaded lipidic-nano drug delivery systems; formulation, therapeutic efficacy, and pharmacokinetics.

AIM: Nano drug delivery systems can provide the opportunity to reduce side effects and improve the therapeutic aspect of a variety of drugs. Bortezomib (BTZ) is a proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma. Severe side effects of BTZ are the major dose-limiting factor. Particulate drug delivery systems for BTZ are polymeric and lipidic drug delivery systems. This review focussed on lipidic-nano drug delivery systems (LNDDSs) for the delivery of BTZ. RESULTS: LNDDSs including liposomes, solid lipid nanoparticles, and self-nanoemulsifying drug delivery systems showed reduce systemic side effects, improved therapeutic efficacy, and increased intestinal absorption. Besides LNDDSs were used to target-delivery of BTZ to cancer. CONCLUSION: Overall, LNDDSs can be considered as a novel delivery system for BTZ to resolve the treatment-associated restrictions.

Preparation and characterization of cyclodextrin nanosponges for bortezomib delivery.

BACKGROUND: Bortezomib (BTZ) as an anticancer drug has been used through the injection pathway. RESEARCH DESIGN AND METHODS: Two types of Cyclodextrin nanosponges (CDNSs) were synthesized and studied by DLS, TEM, FTIR, and DSC instruments for BTZ delivery. Both carriers were analyzed for loading efficiencies and in-vitro release. Cell studies and intestinal permeability of selected CDNS were determined using MTT and SPIP method, respectively. RESULTS: Both types of CDNSs, encapsulated BTZ in their nano-porous structure, but better loading was shown in CDNS 1:4. FTIR and DSC results proved considerable encapsulation of BTZ into CDNSs. The slow and prolonged release profile was observed for CDNS 1:4 in comparison with CDNS 1:2. Based on in-vitro results, BTZ-CDNS 1:4 was chosen as a selected nanosystem for further analysis. This nontoxic carrier revealed considerable uptake (93.9% in 3 h) against the MCF-7 cell line but indicated higher IC50 in comparison with the plain drug. This carrier also could improve the rat intestinal permeability of BTZ almost 5.8 times. CONCLUSION: CDNS 1:4 has the ability to be introduced as a nontoxic carrier for BTZ delivery with its high loading, controlled release manner, high cellular uptake, and permeability improvement characteristics.