Oral delivery of posaconazole-loaded phospholipid-based nanoformulation: Preparation and optimization using design of experiments, machine learning, and TOPSIS.

Phospholipid-based nanosystems show promising potentials for oral administration of hydrophobic drugs. The study introduced a novel approach to optimize posaconazole-loaded phospholipid-based nanoformulation using the design of experiments, machine learning, and Technique for Order of Preference by Similarity to the Ideal Solution. These approaches were used to investigate the impact of various variables on the encapsulation efficiency (EE), particle size, and polydispersity index (PDI). The optimized formulation, with %EE of âˆ¼ 74 %, demonstrated a particle size and PDI of 107.7 nm and 0.174, respectively. The oral pharmacokinetic profiles of the posaconazole suspension, empty nanoformulation + drug suspension, and drug-loaded nanoformulation were evaluated. The nanoformulation significantly increased maximum plasma concentration and the area under the drug plasma concentration-time curve (∼3.9- and 6.2-fold, respectively) and could be administered without regard to meals. MTT and histopathological examinations were carried out to evaluate the safety of the nanoformulation and results exhibited no significant toxicity. Lymphatic transport was found to be the main mechanism of oral delivery. Caco-2 cell studies demonstrated that the mechanism of delivery was not based on an increase in cellular uptake. Our study represents a promising strategy for the development of phospholipid-based nanoformulations as efficient and safe oral delivery systems.

Bile salt-enriched vs. non-enriched nanoparticles: comparison of their physicochemical characteristics and release pattern.

Bile salts were first used in the preparation of nanoparticles due to their stabilizing effects. As time went by, they attracted much attention and were increasingly employed in fabricating nanoparticles. It is well accepted that the physicochemical properties of nanoparticles are influential factors in their permeation, distribution, elimination and degree of effectiveness as well as toxicity. The review of articles shows that the use of bile salts in the structure of nanocarriers may cause significant changes in their physicochemical properties. Hence, having information about the effect of bile salts on the properties of nanoparticles could be valuable in the design of optimal carriers. Herein, we review studies in which bile salts were used in preparing liposomes, niosomes and other nanocarriers. Furthermore, the effects of bile salts on entrapment efficiency, particle size, polydispersity index, zeta potential, release profile and stability of nanoparticles are pointed out. Finally, we debate how to take advantage of bile salts potential for preparing desirable nanocarriers.

Preparation of multivesicular liposomes for the loco-regional delivery of Vancomycin hydrochloride using active loading method: drug release and antimicrobial properties.

Over the last few years, among controlled-release delivery systems, multivesicular liposomes (MVLs) have attracted attention due to their unique benefits as a loco-regional drug delivery system. Considering the clinical limitations of the current treatment strategies for osteomyelitis, MVLs can be a suitable carrier for the local delivery of effective antibiotics. This study aimed to prepare vancomycin hydrochloride (VAN HL) loaded MVLs using the active loading method which to the best of our knowledge has not been previously reported. Empty MVLS were prepared by the double emulsion (w/o/w) method and VAN HL was loaded into the prepared liposomes by the ammonium gradient method. After full characterization, the release profile of VAN HL from MVLs was assessed at two different pH values (5.5 and 7.4), and compared with the release profile of the free drug and also passively loaded MVLs. In vitro antimicrobial activities were evaluated using the disc diffusion method. Our results demonstrated that the encapsulation efficiency was higher than 90% in the optimum actively loaded MVL. The free VAN HL was released within 6-8 h, while the passively loaded MVLs and the optimum actively loaded MVL formulation released the drug in 6 days and up to 19 days, respectively. The released drug showed effective antibacterial activity against osteomyelitis-causing pathogens. In conclusion, the prepared formulation offered the advantages of sustained-release properties, appropriate particle size as well as being composed of biocompatible materials, and thus could be a promising candidate for the loco-regional delivery of VAN HL and the management of osteomyelitis.

Amphotericin B Pharmacokinetics: Inter-strain Differences in Rats Following Intravenous Administration of the Most Commonly Marketed Formulations of the Drug.

Background: Amphotericin B (AmB) is the first-line drug to treat invasive fungal infections. However, its delivery to the body and clinical use faces many challenges because of its poor solubility, poor pharmacokinetics, and severe nephrotoxicity. Objectives: Due to the necessity for designing safer and more effective nanocarriers for AmB and the importance of preclinical pharmacokinetic studies in evaluating these novel drug delivery systems, the present study was framed to explore the influence of rat strain on the pharmacokinetic profile of this drug. Methods: Twenty-four Wistar and Sprague-Dawley (SD) rats were intravenously injected with 1 mg/kg AmB as Fungizone or AmBisome, which are the two most commonly marketed formulations of the drug. Blood samples were collected before and at regular intervals up to 24 h after administration. Drug concentration was analyzed by a validated HPLC method, and pharmacokinetic parameters were determined by the non-compartmental method. Results: Irrespective of the type of formulation, the AUC0-t and AUC0-∞ values were significantly higher (P < 0.001), and Cl as an important PK parameter was markedly lower (P < 0.001) in SD rats compared to the Wistar strain. For Fungizone, the mean Cl values in SD and Wistar rats were 206.90 and 462.95 mL/h/kg (P < 0.001), respectively. The apparent volume of distribution (Vss) was also lower in SD rats compared to Wistar; however, for AmBisome, the difference in Vss was not statistically significant. Our further investigation suggested that the higher amount of total protein in the SD strain may justify the higher plasma concentrations and lower Cl and Vss of amphotericin B in this strain compared to the Wistar strain. Conclusions: Overall, following intravenous administration of AmB, there were significant differences in the pharmacokinetic parameters of the drug between two rat strains for both formulations. The obtained data is important for correctly interpreting experimental data from different research groups.

Berberine-phospholipid nanoaggregate-embedded thiolated chitosan hydrogel for aphthous stomatitis treatment.

Aim: This study aimed to develop nanoaggregates of berberine-phospholipid complex incorporated into thiolated chitosan (TCS) hydrogel for the treatment of aphthous stomatitis. Methods: The berberine-phospholipid complex was formulated through the solvent evaporation technique and assembled into nanoaggregates. TCS was synthesized through the attachment of thioglycolic acid to chitosan (CS). Nanoaggregates-TCS was prepared by the incorporation of nanoaggregates into TCS and underwent in vitro and in vivo tests. Results: Nanoaggregates-TCS exhibited prolonged release of berberine. The mucoadhesive strength of nanoaggregates-TCS increased 1.75-fold compared with CS hydrogel. In vivo studies revealed the superior therapeutic efficacy of nanoaggregates-TCS compared with that of other groups. Conclusion: Due to prolonged drug release, appropriate residence time and anti-inflammatory effects, nanoaggregates-TCS is an effective system for the treatment of aphthous stomatitis.

Piperine liposome-embedded in hyaluronan hydrogel as an effective platform for prevention of postoperative peritoneal adhesion.

This study aimed to prepare piperine (PIP) loaded liposomes in hyaluronic acid (HA) hydrogel to provide a hybrid superstructure for postoperative adhesion prevention. Liposomes were prepared using thin-film hydration method. The optimised formulation was characterised by size, SEM, TEM, FTIR, encapsulation efficiency (EE)% (w/w), and release pattern. Liposome-in-hydrogel formulation was investigated by rheology, SEM, and release studies. The efficacy was evaluated in a rat peritoneal abrasion model. EE% (w/w) increased with increasing lipid concentration from 10 to 30; however, a higher percentage of Chol reduced EE% (w/w). The optimised liposome (EE: 68.10 ± 1.71% (w/w), average diameter: 513 ± 8 nm, PDI: 0.15 ± 0.04) was used for hydrogel embedding. No sign of adhesion in 5/8 rats and no collagen deposition confirmed the in vivo effectiveness of the optimised formulation. Overall, providing a sustained delivery of PIP, the developed liposome-in-hydrogel formulation can be a promising carrier to prevent postoperative adhesion.

Biocompatible phospholipid-based mixed micelles for posaconazole ocular delivery: Development, characterization, and in - vitro antifungal activity.

Current study intended to prepare and evaluate phospholipid-based, mixed micelles (MMs) to improve the ocular delivery of posaconazole (POS), a broad-spectrum antifungal drug. For this, MMs based on egg phosphatidylcholine (EPC), as the main component, in combination with various bile salts (sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC)) or non-ionic surfactants (Pluronic® F-127, Pluronic® F-68, Tween 80, Labrasol® ALF, and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) were prepared. Particle size, polydispersity index, zeta potential and entrapment efficiency were evaluated to optimize the composition and preparation method of the MMs. Finally, morphology, stability, in vitro release pattern, and in vitro antifungal activity of the optimized formulation were investigated. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30, prepared by the thin-film hydration method, showed more appropriate features. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30 showed more appropriate features, including an entrapment efficiency (EE) greater than 80%, spherical shape morphology, an average particle size of about 58 nm, desirable stability over a month, slow-release without a noticeable initial burst, and a significantly higher in vitro antifungal activity in comparison with the drug suspension. Therefore, this formulation was selected as the optimal MMs and could be considered as a promising carrier for topical ocular delivery of POS.

Cerasome Versus Liposome: A Comparative Pharmacokinetic Analysis Following Intravenous Administration into Rats.

Background: Cerasomes, due to their external siloxane network, demonstrate markedly higher physicochemical stability and, therefore, easier handling and storage than liposomes. Objectives: The main objective of this study was to compare the pharmacokinetics (PK) of cerasome and liposome following intravenous administration. The PK of PEGylated and non-PEGylated cerasomes was also compared to see whether the presence of a hydrophilic siloxane network on the surface of cerasomes can play the role of polyethylene glycol (PEG) in increasing the blood circulation of these vesicles. Methods: Silver sulfide (Ag2S) quantum dots (Qds)-loaded PEGylated and non-PEGylated cerasomes and PEGylated liposomes were fabricated and thoroughly characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and in vitro stability. For pharmacokinetic evaluation, the free Qds and the selected formulations were intravenously injected into rats, and blood samples were collected for up to 72 hours. Pharmacokinetic parameters were calculated by the non-compartmental method. Results: Both cerasomal and liposomal carriers significantly improved the PK of Qds. For example, the elimination half-life (t1/2) and the area under the plasma concentration-time curve from time 0 to time infinity (AUC0-∞) for the free Qds were 4.39 h and 8.01 µg/mL*h and for cerasomal and liposomal formulations were 28.82 versus 26.95 h and 73.25 versus 62.02 µg/mL*h, respectively. However, compared to each other, the plasma concentration-time profiles of PEGylated cerasomes and liposomes displayed similar patterns, and the statistical comparison of their pharmacokinetic parameters did not show any significant difference between the two types of carriers. For PEGylated cerasomes, t1/2 and AUC0-∞ values were respectively 1.6 and 3.3 times greater than the classic cerasome, indicating that despite the presence of a hydrophilic siloxane network, the incorporation of PEG is necessary to reduce the clearance of cerasomes. Conclusions: The comparable PK of PEGylated cerasomes and liposomes, along with the higher physicochemical stability of cerasomes, can be considered an important advantage for the clinical application of cerasomes. Additionally, the easy surface functionalizing ability of cerasomes confers a dual advantage over liposomes. The study findings also showed that the presence of a hydrophilic siloxane network on the surface of cerasomes alone is not enough to make them circulate long.

Piperine-loaded electrospun nanofibers, an implantable anticancer controlled delivery system for postsurgical breast cancer treatment.

Tumorectomy followed by radiotherapy, hormone, and chemotherapy, are the current mainstays for breast cancer treatment. However, these strategies have systemic toxicities and limited treatment outcomes. Hence, there is a crucial need for a novel controlled release delivery system for implantation following tumor resection to effectively prevent recurrence. Here, we fabricated polycaprolactone (PCL)-based electrospun nanofibers containing piperine (PIP), known for chemopreventive and anticancer activities, and also evaluated the impact of collagen (Coll) incorporation into the matrices. In addition to physicochemical characterization such as morphology, hydrophilicity, drug content, release properties, and mechanical behaviors, fabricated nanofibers were investigated in terms of cytotoxicity and involved mechanisms in MCF-7 and 4T1 breast tumor cell lines. In vivo antitumor study was performed in 4T1 tumor-bearing mice. PIP-PCL75-Coll25 nanofiber was chosen as the optimum formulation due to sustained PIP release, good mechanical performance, and superior cytotoxicity. Demonstrating no organ toxicity, animal studies confirmed the superiority of locally administered PIP-PCL75-Coll25 nanofiber in terms of inhibition of growth tumor, induction of apoptosis, and reduction of cell proliferation compared to PIP suspension, blank nanofiber, and the control. Taken together, we concluded that PIP-loaded nanofibers can be introduced as a promising treatment for implantation upon breast tumorectomy.

The Impact of Process and Formulation Parameters on the Fabrication of Efavirenz Nanosuspension to Improve Drug Solubility and Dissolution.

Background: Efavirenz nanosuspensions (EZ-NSs) were developed by the wet milling method as the most promising top-down nanosizing technique. Different process and formulation parameters were studied and optimized to produce appropriate EZ-NS in suitable conditions to enhance drug dissolution. Methods: In the preliminary studies, various polymeric stabilizers, including Pluronic F68, sodium carboxymethylcellulose (CMC), hydroxypropyl methylcellulose (HPMC), and polyvinyl alcohol (PVA), as well as different sizes and weight of milling beads were used to prepare NSs. The effect of sodium lauryl sulfate (SLS) concentration on the NS properties was also evaluated. The influence of other formulation and process parameters, including polymer concentration, milling speed, and milling time, on the particle size and distribution of NSs were investigated using Box-Behnken design. The optimized freeze-dried nanosuspension was characterized by redispersibility, physicochemical properties, and stability. Results: A combination of PVA and SLS was selected as steric and electrostatic stabilizers. The optimum EZ-NS displayed a uniform size distribution with a mean particle size and zeta potential of 254.4 nm and 21.1 mV, respectively. The solidified nanosuspension was well redispersed to the original nanoparticles. Significantly enhanced aqueous solubility (about 11-fold) and accelerated dissolution rate were observed for the optimized formulation. This could be attributed to the reduced particle size and partial amorphization of EZ during the preparation process, studied by X-ray diffraction. Accelerated studies confirmed the stability of the optimum freeze-dried formulation over the examined period of three months. Conclusions: Optimization of different variables led to the formation of EZ-NSs with desired properties through wet milling in a very short time compared to the previous study and therefore reduced production costs. This formulation seems to be a suitable approach for solubility and dissolution enhancement of EZ and may have a great potential to improve the drug's oral bioavailability.

Doxorubicin-Loaded Multivesicular Liposomes (DepoFoam) as a Sustained Release Carrier Intended for Locoregional Delivery in Cancer Treatment: Development, Characterization, and Cytotoxicity Evaluation.

Background: Despite the advantages of direct intratumoral (IT) injection, the relatively rapid withdrawal of most anti-cancer drugs from the tumor due to their small molecular size limits the effectiveness of this method of administration. To address these limitations, recently, increasing attention has been directed to using slow-release biodegradable delivery systems for IT injection. Objectives: This study aimed to develop and characterize a doxorubicin-loaded DepoFoam system as an efficient controlled-release carrier to be employed for locoregional drug delivery in cancer treatment. Methods: Major formulation parameters, including the molar ratio of cholesterol to the main lipid [Chol/egg phosphatidylcholine (EPC)], triolein (TO) content, and lipid-to-drug molar ratio (L/D), were optimized using a two-level factorial design approach. The prepared batches were evaluated for encapsulation efficiency (EE) and percentage of drug release (DR) after 6 and 72 hours as dependent variables. The optimum formulation (named DepoDOX) was further evaluated in terms of particle size, morphology, zeta potential, stability, Fourier-transform infrared spectroscopy, in vitro cytotoxicity, and hemolysis. Results: The analysis of factorial design indicated that TO content and L/D ratio had a negative effect on EE; between these two, TO content had the greatest effect. The TO content was also the most significant component, with a negative effect on the release rate. The ratio of Chol/EPC showed a dual effect on the DR rate. Using a higher percentage of Chol slowed down the initial release phase of the drug; nevertheless, it accelerated the DR rate in the later slow phase. DepoDOX were spherical and honeycomb-like structures (≈ 9.81 µm) with a desired sustained release profile, as DR lasted 11 days. Its biocompatibility was confirmed by the results of cytotoxicity and hemolysis assays. Conclusions: The in vitro characterization of optimized DepoFoam formulation demonstrated its suitability for direct locoregional delivery. DepoDOX, as a biocompatible lipid-based formulation, showed appropriate particle size, high capability for encapsulating doxorubicin, superior physical stability, and a markedly prolonged DR rate. Therefore, this formulation could be considered a promising candidate for locoregional drug delivery in cancer treatment.

Particle Size Tailoring of Quercetin Nanosuspensions by Wet Media Milling Technique: A Study on Processing and Formulation Parameters.

Background: A large number of new substances have insufficient biopharmaceutical properties for oral administration caused by their slow dissolution rate and poor solubility. Objective: The purpose of our experiment was to improve the physicochemical properties of a hydrophobic drug, quercetin, by the nanomilling approach. Methods: Quercetin nanosuspensions were prepared using a wet-milling method followed by lyophilization. Stabilizer type and ratio, drug content, milling time, and bead size were identified as critical variables, and their impacts on quercetin particle size were assessed. The optimized nanocrystal was characterized by its morphology, crystallinity, molecular interactions, saturation solubility, and dissolution properties. Results: At optimized process conditions of milling at 500 rpm for 18 cycles of grinding with 0.3 - 0.4 mm zirconium oxide beads, minimum particle size, and PDI values were 281.21 nm and 0.22, respectively. Nanocrystals showed rod-like nanostructures, and XRD scans confirmed a decrease in drug crystallinity. The optimized formulation showed increased solubility and dissolution rate, as well as good physical stability. Conclusions: Particle size reduction by media milling technique was an efficient method for the solubility enhancement of hydrophobic drugs.

Sirolimus-exuding core-shell nanofibers as an implantable carrier for breast cancer therapy: preparation, characterization, in vitro cell studies, and in vivo anti-tumor activity.

OBJECTIVE: Breast cancer accounts for significant mortality worldwide. Here, we develop a localized, sustained-release delivery system for breast cancer therapy. METHODS: Sirolimus (SIR) core-shell nanofibers (NFs) are fabricated by coaxial electrospinning with poly(ε-caprolactone) (PCL) for the core and chitosan and PCL for the shell. The NFs were characterized by SEM, AFM, TEM, XRD, FTIR, water uptake, water contact angle, mechanical properties, drug content, and in vitro release. In vitro and in vivo anticancer effects were investigated. RESULTS: A sustained release behavior is observed during 480 h that is more extended compared to monoaxial NFs. In vitro cytotoxicity and Annexin V/propidium iodide assays indicate that SIR-loaded coaxial NFs are effective in inhibiting proliferation of 4T1 and MCF-7 cells. Implantation of SIR NFs in 4T1 breast tumor-bearing mice inhibits tumor growth significantly compared to free drug. Histopathological examination shows that suppression of tumor growth by SIR NFs is associated with apoptotic cell death. Furthermore, anti-cancer effects are also confirmed by decreased expression levels of Ki-67, MMP-2, and MMP-9. Histological observation of organs, serological analyses, and the lack of body weight changes indicate in vivo safety of SIR NFs. CONCLUSIONS: Altogether, we show here that incorporation of SIR into core-shell NFs could act as an effective drug release depot and induce a sustained antitumor response.

Multivesicular liposomal depot system for sustained delivery of risperidone: development, characterization, and toxicity assessment.

OBJECTIVE: Considering the limitations of conventional risperidone (RSP) therapies, the present research characterizes the usefulness of multivesicular liposomes (MVLs) as an efficient controlled-release carrier for this widely used antipsychotic drug, to be employed for the treatment of schizophrenia. METHODS: A 23 full factorial design based on three independent variables was implemented to plan the experiments: the molar ratios of lipid to the drug, triolein to phospholipid, and cholesterol to phospholipid. The impacts of these parameters on the risperidone encapsulation efficiency and its release pattern within the first 24 and 48 h were investigated as dependent variables. Then, the optimized liposomal system was further in-depth analyzed in terms of size, morphological and structural features, release profile over 15 days, biocompatibility, and stability. RESULTS: Optimized formulation parameters gave rise to MVLs possessing a spherical morphology with a median diameter of about 8 µm, a relatively narrow size distribution (span value of 1.49), and an encapsulation efficiency of 57.6%. These carriers not only exhibited a sustained-release behavior in vitro, lasting until the end of the 15 days but also underwent a negligible change in their size and RSP incorporation over two months at refrigerator condition. Furthermore, in vitro cytotoxicity and hemolysis assessments revealed that the optimized MVL formulation is biocompatible. CONCLUSION: This study revealed the potential of MVLs as a promising system for the delivery of RSP and could open a new vista for the successful management of schizophrenia.

Pharmacokinetics, tissue distribution and peritoneal retention of Ag2S quantum dots following intraperitoneal administration to mice.

OBJECTIVES: To investigate the pharmacokinetics, biodistribution and peritoneal retention of Ag2S quantum dots (Qds) after intraperitoneal (IP) injection into mice and to compare the results with those reported for the intravenous (IV) injection of these particles. METHODS: Ag2S Qds was prepared by a simple one-step co-precipitation method and was injected intraperitoneally into mice. Six animals were sacrificed at predetermined time points, and blood, peritoneal content and tissue samples were collected. Ag concentration that represents the concentration of Qds was analysed by atomic absorption spectrophotometry. KEY FINDINGS: Detectability of Qds in the peritoneal sample up to 2 h indicated that, compared with small drug molecules, the absorption of Ag2S Qds from the peritoneal cavity occurred at a slower rate. The AUC tissue/AUC blood ratio in the liver and intestine after IP injection (0.55 and 0.98, respectively) was considerably lower than those for the bolus injection (217 and 94, respectively), while this ratio in the spleen and lungs was markedly higher than the IV route. CONCLUSIONS: Overall, the obtained results suggest that IP injection of Ag2S Qds could be more effective for drug delivery to/imaging of the spleen and lungs, whereas the IV injection for the drug delivery to/imaging of the liver and intestine.

An investigation of affecting factors on MOF characteristics for biomedical applications: A systematic review.

Metal-organic frameworks (MOFs) are a fascinating class of crystalline porous materials composed of metal ions and organic ligands. Due to their attractive properties, MOFs can potentially offer biomedical field applications, such as drug delivery and imaging. This study aimed to systematically identify the affecting factors on the MOF characteristics and their effects on structural and biological characteristics. An electronic search was performed in four databases containing PubMed, Scopus, Web of Science, and Embase, using the relevant keywords. After analyzing the studies, 20 eligible studies were included in this review. As a result, various factors such as additives and organic ligand can influence the size and structure of MOFs. Additives are materials that can compete with ligand and may affect the nucleation and growth processes and, consequently, particle size. The nature and structure of ligand are influential in determining the size and structure of MOF. Moreover, synthesis parameters like the reaction time and initial reagents ratio are critical factors that should be optimized to regulate the size and structure. Of note is that the nature of the ligand and using a suitable additive can control the porosity of MOF. The more extended ligands aid in forming large pores. The choice of metallic nodes and organic ligand, and the MOF concentration are important factors since they can determine toxicity and biocompatibility of the final structure. The physicochemical properties of MOFs, such as hydrophobicity, affect the toxicity of nanoparticles. An increase in hydrophobicity causes increased toxicity of MOF. The biodegradability of MOF, as another property, depends on the organic ligand and metal ion and environmental conditions like pH. Photocleavable ligands can be served for controlled degradation of MOFs. Generally, by optimizing these affecting factors, MOFs with desirable properties will be obtained for biomedical applications.

An enzyme-mediated controlled release system for curcumin based on cyclodextrin/cyclodextrin degrading enzyme.

In this study, an enzyme-triggered system based on ß-cyclodextrin (ß-CD) has been developed to achieve controlled release of hydrophobic drugs in the presence of maltogenic amylase (MAase). The inclusion complex formation of curcumin (CUR), as a model anticancer compound, with ß-CD was characterized by fluorescence and Fourier transform infrared (FTIR) spectroscopy. CUR was loaded into ß-CD with an encapsulation efficiency of approximately 30 %. The in vitro profiles of CUR release from ß-CD showed that 100 % of the drug was released after one hour incubation in the presence of MAase with cyclodextrin degrading activity. Fluorescence microscopy images indicate a significantly greater cellular uptake of CUR using ß-CD-CUR/MAase system compared to ß-CD-CUR inclusion complex without MAase. The ß-CD-CUR/MAase system exhibited lower IC50 values and greater anti-proliferative effects in comparison with free CUR and ß-CD-CUR in MCF-7 and Huh-7 cancer cells. The results from fluorescence microscopy and flow cytometric assay using the acridine orange/ethidium bromide and Annexin V-PE/7-AAD staining suggest that the ß-CD-CUR/MAase system exhibited higher cytotoxic and apoptotic effects on cancer cells compared to other formulations. This triggered release of CUR in the presence of MAase is owing to the ß-CD degradation by MAase resulting ring opening and chain scission in ß-CD. We demonstrate that this enzyme-mediated controlled release system has a potential application for controlled release of poorly water-soluble drugs or hydrophobic compounds such as CUR.

Ameliorative effect of a nano chromium metal-organic framework on experimental diabetic chronic kidney disease.

Metal-Organic Frameworks (MOFs) are a new class of crystalline porous structures which can be used as a novel structure in diverse fields of medical science. Several studies have shown that chromium supplementation can be effective in amelioration of biochemical parameters of diabetes and its renal complications. Therefore, a chromium-containing MOF (DIFc) was synthetized by nanochelating technology in the present study and then its effect on biochemical indices in diabetic rats was evaluated. Diabetes was induced by high-fat diet consumption and streptozotocin (35 mg/kg) injection and then the treatment started 8 weeks after disease induction and continued for 8 weeks. The results showed that DIFc treatment decreased HOMA-IR index, blood urea nitrogen, uric acid and malondialdehyde in plasma samples. This nano MOF also reduced albumin, malondialdehyde and 8-isoprostane in urine specimen, while it increased creatinine clearance. In conclusion, DIFc MOF demonstrated promising results in the present study, indicating that it can be developed and evaluated in future investigations with the aim of designing a novel agent for management of diabetes and its renal complications.

The Impact of Surfactant Composition and Surface Charge of Niosomes on the Oral Absorption of Repaglinide as a BCS II Model Drug.

BACKGROUND: Niosomes, bilayer vesicles formed by the self-assembly of nonionic surfactants, are receiving increasing attention as potential oral drug delivery systems but the impact of niosomal formulation parameters on their oral capability has not been studied systematically. The aim of this study was to investigate the impact of surfactant composition and surface charge of niosomes in enhancing oral bioavailability of repaglinide (REG) as a BCS II model drug. METHODS: Niosomes (13 formulations) from various nonionic surfactants having HLB in the range of 4-28 (Tweens, Spans, Brijs, Myrj, poloxamer 188, TPGS and Labrasol) were prepared and characterized concerning their loading efficiency, hydrodynamic diameter, zeta potential, drug release profile, and stability. The oral pharmacokinetics of the selected formulations were studied in rats (8 in vivo groups). RESULTS: The results revealed that type of surfactant markedly affected the in vitro and in vivo potentials of niosomes. The Cmax and AUC values of REG after administration of the selected niosomes as well as the drug suspension (as control) were in the order of Tween 80> TPGS> Myrj 52> Brij 35> Span 60≈Suspension. Adding stearyl amine as a positive charge-inducing agent to the Tween 80-based niosomes, resulted in an additional increase in drug absorption and values of AUC and Cmax were 3.8- and 4.7-fold higher than the drug suspension, respectively. CONCLUSION: Cationic Tween 80-based niosomes may represent a promising platform to develop oral delivery systems for BCS II drugs.

Tuning the Physicochemical Characteristics of Particle-Based Carriers for Intraperitoneal Local Chemotherapy.

Over the last few decades, intraperitoneal (IP) local drug delivery, providing high drug concentrations with prolonged retention in the peritoneal cavity, has opened a new horizon for the management of life-threatening peritoneal disorders, such as peritoneal carcinomatosis (PC). However, clinical translation of this strategy is hampered by several hurdles, namely premature clearance of small-sized molecules from the peritoneum, limited distribution within the peritoneal space and inadequate penetration into the target tissues. To address these challenges, incorporation of therapeutic agents into the particulate-based drug delivery systems has brought new hope in this direction. Nonetheless, as yet, there has been no formulation specifically approved for IP delivery. To gain this goal, it is crucial to have a detailed understanding of the correlation between the physicochemical characteristics of particle-based carriers and their biological fate and anticancer efficacy after IP administration. The main focus of this review, therefore, concerns the significance of these characteristics, namely composition, particle size, charge, coating and presence of targeting moieties in the design of carriers for successful IP delivery. Graphical Abstract Physicochemical characteristics of particle-based carriers influence their peritoneal residence time, biological fate and anticancer efficacy after intraperitoneal administration.