Formulation and evaluation of taste-masked oral disintegrating tablet containing tolterodine-loaded montmorillonite.

Background and purpose: The present study aimed to obtain a taste-masked oral disintegrating tablet (ODT) containing tolterodine tartrate (TT) intercalated into montmorillonite (MMT). Experimental approach: The TT-MMT hybrid was prepared by ion exchange reaction. The effect of the initial concentration of TT, MMT, temperature, and pH on the encapsulation efficiency (EE) % of the drug in MMT was evaluated. The selected TT-MMT hybrid was characterized by X-ray diffraction (XRD), Fourier transforms infrared (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Then, the optimized TT-MMT hybrid was incorporated in the ODT prepared by direct compression method and taste-masking assessment performed by a human test panel. Findings/Results: The EE% of TT was in the range of 22.67 to 71.06% in different formulations. It was found that increases in MMT concentration significantly increased EE%. DSC and XRD studies indicated that the TT was intercalated in the MMT interlayer space in an amorphous or molecular state. In-vitro release studies at pH 6.8 showed that the amount of the drug released from the TT-MMT hybrid was negligible for the first 3 min. The post-compression of ODT also showed satisfactory results in terms of friability, hardness, disintegration time, and taste. Conclusion and implications: MMT-ODT could be a suitable vehicle for the taste masking of TT, with the potential for use in patients with swallowing problems.

Chrysin loaded bilosomes improve the hepatoprotective effects of chrysin against CCl4 induced hepatotoxicity in mice.

In the present work, chrysin loaded bilosomes were formulated, characterized and evaluated to enhance the hepatoprotective activity of drug. Accordingly, chrysin loaded bilosomes were prepared by applying the thin film hydration method; also, fractional factorial design was used to optimize the production conditions of nanoformulations. The prepared formulations were subjected to different methods of characterization; then the hepatoprotective activity of the optimized one was evaluated in the CCl4 hepatointoxicated mice model. Optimized chrysin loaded bilosomes showed a spherical shape with a particle size of 232.97 ± 23 nm, the polydispersity index of 0.35 ± 0.01, the zeta potential of -44.5 ± 1.27 mv, the entrapment efficiency of 96.77 ± 0.18%, the drug loading % of 6.46 ± 0.01 and the release efficiency of 42.25 ± 1.04 during 48 h. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay demonstrated the superiority of the anti-oxidant potential of chrysin loaded bilosomes, as compared to pure chrysin. This was in agreement with histopathological investigations, showing significant improvement in serum hepatic biomarkers of CCl4 intoxicated mice treated with chrysin loaded bilosomes, as compared with free chrysin. These results, thus, showed the potential use of bilosomes to enhance the hepatoprotective activity of chrysin via oral administration.

Formulation and physicochemical characterization of azithromycin-loaded cubosomes.

Background and purpose: Azithromycin (AZ) is a macrolide antibiotic that is soluble in saliva pH; its bitter taste can be well sensed, decreasing the ability of the patient to get the drug. Thus, handling such a bitter taste is challenging in developing the oral formulation. A wide range of methods has been applied to tackle this problem. Cubosomes are considered nanoparticles forming cubic three-dimensional structures with a taste-masking effect. This research aimed to apply cubosomes to mask AZ's bitter taste. Experimental approach: Cubosomes which contained AZ were obtained by applying the film hydration method. Design expert software (version 11) was then employed for optimizing cubosomes that contained the drug. The encapsulation efficiency, particle size as well as polydispersity index of drug-loaded cubosomes were then subjected to evaluation. Assessment of particle morphology was done through SEM. The antimicrobial qualities of AZ-loaded cubosomes were then assessed by utilizing the disc diffusion method. Then, the taste masking study was carried out by referring to human volunteers. Finding/Results: AZ-loaded cubosomes were spherical in terms of shape and in the 166-272 nm range, with a polydispersity index of 0.17-0.33 and encapsulation efficiency of 80-92%. The results related to the microbial culture revealed that the antimicrobial qualities related to AZ-loaded cubosomes were like those of AZ. The results obtained by taste evaluation also revealed that the cubosomes could well mask the drug's bitter taste. Conclusion and implications: These findings, thus, revealed that while the antimicrobial impact of AZ is not under the influence of loading in cubosomes, its taste could be well improved.

Preparation, optimization, and in vitro-in vivo evaluation of sorafenib-loaded polycaprolactone and cellulose acetate nanofibers for the treatment of cutaneous leishmaniasis.

The most common form of leishmaniasis is cutaneous leishmaniasis (CL). The major difficulties in the treatment of leishmaniasis include emergence of resistance, toxicity, long-term treatment, and the high cost of the current drugs. Although the therapeutic effect of sorafenib (SF) has been demonstrated in both in vitro and in vivo models of Leishmania infection, the therapeutic applications are limited due to severe drug-related toxicity; this is, in turn, due to non-specific distribution in the body. Thus, topical delivery has the advantage of the site directed delivery of SF. This research study evaluated SF-loaded hybrid nanofibers (NFs) which were composed of polycaprolactone (PCL) and cellulose acetate (CA) for the CL topical treatment. Accordingly, SF-loaded hybrid NFs were prepared using the electrospinning method. Formulation variables including total polymer concentration, drug/polymer ratio, and CA concentration were optimized using a full factorial design. The prepared SF-loaded NFs were then characterized for morphology, diameter, encapsulation efficiency (EE)%, drug loading (DL) %, and percentage of release efficiency during a 24-h period (RE24h%); the mechanical characteristics were also considered. The physical state of the drug in the optimized NF was evaluated by the X-ray diffraction analysis. Finally, its in vivo efficacy was determined in L. major-infected mice. The optimized formulation had a smooth, cylindrical, non-beaded shape fiber with a diameter of 281.44 nm, EE of 97.96%, DL of 7.48%, RE of 51.05%, ultimate tensile strength of 1.08 MPa, and Young's moduli of 74.96 MPa. The XRD analysis also demonstrated the amorphous state of SF in NF. Further, the in vivo results displayed the higher anti-leishmanial activity of the SF-loaded hybrid NF by efficiently healing lesion and successfully reducing the parasite burden. This, thus, indicated the potential of the clinical capability of the SF-loaded hybrid NF for the effective treatment of CL.

Development and evaluation of wafer loaded with sertaconazole solid dispersion for the treatment of oral candidiasis

Abstract Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.

Preparing simvastatin nanoparticles by a combination of pH-sensitive and timed-release approaches for the potential treatment of ulcerative colitis.

In this study, an emulsion solvent evaporation method was used to produce Eudragit RL (ERL) nanoparticles (NPs) loaded with simvastatin (SIM) for the treatment of ulcerative colitis (UC). Accordingly, the effects of different formulation variables on the properties of NPs were evaluated using the Box-Behnken design. The optimized NPs were then coated by Eudragit FS30D (EFS30D). Drug release was studied in different physiological environments. Colitis was induced by 3% of acetic acid in rats, which received NPs of SIM (10 mg/kg/day), mesalazine (150 mg/kg/day), blank NPs and normal saline orally for 5 days. Macroscopic histopathological evaluation and biochemical analysis, including myeloperoxidase (MPO) activity and malondialdehyde (MDA) level in the colon tissues, were carried out in this study. The optimized SIM-ERL NPs showed the particle size of 182.48 ± 4.57 nm, the polydispersity index of 0.29 ± 0.12, the zeta potential of 26.45 ± 4.57 mV, drug loading % of 34.64 ± 0.48, the encapsulation efficiency % of 98.68 ± 0.69, and the release efficiency % of 35.78 ± 1.37. Coating the optimized NPs with EFS30D caused an increase in particle size and a decrease in the zeta potential of NPs. The optimized SIM-EFS30D/RL NPs improved the macroscopic and histopathological scores. Also, MPO activity and MDA level were reduced significantly by NPs, as compared to the control group. Therefore, this drug delivery system can be an alternative to the previous treatments of UC.

Evaluation of thermosensitive chitosan hydrogel containing gefitinib loaded cellulose acetate butyrate nanoparticles in a subcutaneous breast cancer model.

In the present study, gefitinib loaded cellulose acetate butyrate nanoparticles (Gnb-NPs) were prepared and then incorporated into thermo-sensitive chitosan/ß-glycerophosphate hydrogels for intratumoral administration in mice bearing breast cancer. Accordingly, Gnb-NPs were prepared using the solvent evaporation process and optimized by applying a two-level fractional factorial design. Properties of NPs, including particle size, zeta potential (ZP), polydispersity index (PdI), encapsulation efficiency (EE) % and drug loading (DL) %, were investigated; the optimized Gnb-NPs were then loaded in chitosan hydrogels (Gnb-NPs-Hydrogel). The formulated Gnb-NPs-Hydrogel was assessed in terms of gelling time, release behavior, injectability, swelling and degradation behavior. The anti-cancer efficacy of Gnb-NPs-Hydrogel was evaluated in vitro against the 4 T1 breast cancer cell line and in vivo in breast tumor bearing mice. The optimized formulation showed spherical particles with the size of 156.50 ± 2.40 nm, PdI of 0.20 ± 0.002, ZP of -4.90 ± 0.04 mV, EE of 99.77 ± 0.09 % and DL of 20.59 ± 0.05 %. Incorporating Gnb-NPs into the hydrogel led to the decrease of the drug release rate. Gnb-NPs-Hydrogel displayed a greater cytotoxic effect in comparison to the free Gnb and Gnb-Hydrogel in 4 T1 cancer cells. Furthermore,intratumorallyinjectedGnb-NPs-Hydrogel showed the strongest antitumor efficacy in vivo. The superior performance of Gnb-NPs-Hydrogel, thus, demonstrated its potential for the treatment of breast cancer.

Preparation and characterization of a hydroxypropyl methylcellulose based wafer for simultaneous delivery of phenytoin and insulin as wound dressing material.

In this study, a novel wafer based on Hydroxypropyl methylcellulose (HPMC) was prepared as a wound dressing for the simultaneous delivery of phenytoin (PT) and insulin; evaluation of the cutaneous wound repair property was performed too. Due to its low water solubility, PT was encapsulated in polymeric micelles (PM) by the film hydration method at different polymer/drug ratios and characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP), drug loading (DL) %, entrapment efficiency (EE) %, and drug release. Then, the optimized PT loaded PM (PT-PM) was embedded in the wafers prepared from the HPMC polymer, alone or in combination with Carbopol 940 (CB) and xanthan gum (XG). This wafer also contained a fixed amount of insulin (PT-PM-Insulin-wafer). The obtained wafers were evaluated in terms of morphology, water uptake ability, porosity, bioadhesion and hardness features. Finally, the efficacy of the PT-PM-Insulin-wafer was assessed in full-thickness excision wound models. The optimized PT-PM showed the PS of 84.05 ± 1.80 nm, PdI of 0.28 ± 0.22, ZP of -3.38 ± 0.26 mV, DL of 15.63 ± 0.01%, EE of 92.66 ± 0.08%, and the release efficiency of 59.95 ± 0.03%. The results obtained from the XRD studies of PT-PM also demonstrated the transition of the crystalline nature of the PT to the amorphous form, while FTIR studies showed some intermolecular interaction of PT and the Soluplus® copolymer chain. It was also found that the incorporation of XG into HPMC wafers influenced the microstructure, thus increasing the porosity, water uptake ability and bioadhesion. Compared with other groups, the PT-PM-Insulin-wafer group showed the enhancement of wound closure through increasing collagen deposition and re-epithelialization. The present study, therefore, revealed that the PT-PM-Insulin-wafer group might have very promising applications for wound healing.

Preparation and in vitro evaluation of Vancomycin loaded Montmorillonite-Sodium Alginate topical gel for wound infection

Abstract Despite decades of research, wound healing remains a significant public health problem. This study aimed to develop and evaluate a topical sodium alginate gel containing vancomycin (Van) loaded MMT NPs for wound healing applications. Van was loaded in MMT at different conditions (pHs of 6, 7 and temperatures of 40, 50 °C) (Van/MMT NPs). The optimum formulation (with the smallest particle size and a high value of zeta potential; 270.8 ± 77.35 nm and -35.96 ± 2.73, respectively) showed a high drug-loading capacity (entrapment efficacy of 96%) and a sustained release pattern of Van (95%) over 480 min. The optimum Van/MMT NPs were embedded into the sodium alginate (SA) gel (Van/MMT NPs/SA gel). The Van/ MMT NPs/SA gel showed a sustained and slow release pattern of Van (95%) over 50 h. FTIR tests revealed the electrostatic interaction between MMT and Van. The broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) of Van, Van/ MMT NPs, and Van/MMT NPs/SA gel against Staphylococcus aureus. The results showed the promising antibacterial activity of Van/MMT NPs/SA gel, thus, this gel can be a promising formulation for the management of infected wounds

Fabrication and evaluation of hesperidin loaded polyacrylonitrile/polyethylene oxide nanofibers for wound dressing application.

In this study, hesperidin (HPN) loaded polyacrylonitrile (PAN)/polyethylene oxide (PEO) electrospun nanofibers were prepared for use as wound dressing. Accordingly, HPN loaded hybrid nanofibers were generated via electrospinning. A full factorial design was then applied to evaluate the influence of formulation variables including PEO amount, HPN amount and total polymer amount on the nanofiber features. Fabricated membranes were evaluated in terms of morphology, diameter, entrapment efficiency (EE) %, drug loading (DL) %, release efficiency (RE) %, swelling % and mechanical properties. Analysis of the obtained data showed that the amount of PEO was the most effective factor impacting the swelling and release percentage; by raising the amount of PEO from 20% to 40%, the swelling % and release rate were considerably increased. The optimized nanofibers were found to be non-beaded, smooth and cylindrical with fiber diameter of 126.14 ± 23.96 nm, EE% of 38.58 ± 6.06, DL% of 5.36 ± 0.83, swelling % of 859.90 ± 33.49, RE % of 78.49 ± 0.21, UTS of 0.79 ± 0.13 MPa and Young's moduli of 20.91 ± 2.13 MPa. The physical state of HPN in optimized hybrid nanofibers was examined and the related XRD analysis revealed that HPN was either molecularly dispersed, or it existed in an amorphous state in the nanofibers. The in vivo studies also demonstrated that the wound healing rate in the case of HPN loaded nanofibers was higher when compared with other groups. Moreover, according to H&E and MT stain results, HPN loaded nanofibers did promote the regeneration of skin more effectively, as compared with HPN-free nanofibers. Overall, HPN loaded nanofibers mats prepared in this study have the potential to serve as wound dressings.

In vitro and in vivo evaluation of an ionic sensitive in situ gel containing nanotransfersomes for aripiprazole nasal delivery.

In the current study, a composite in-situ gel formulation containing aripiprazole (APZ) loaded transfersomes (TFS) was developed for the intranasal brain targeting of APZ. APZ loaded TFS were prepared by applying the film hydration method and optimized using an irregular factorial design. The prepared formulations were optimized based on different parameters including particle size, polydispersity index (PdI), zeta potential, encapsulation efficiency (EE) and release efficiency (RE). The optimized APZ-TFS were distributed in an ion-triggered deacetylated gellan gum solution (APZ-TFS-Gel) and evaluated in terms of pH, gelling time, rheological properties and in-vitro release study. The therapeutic efficacy of the best APZ-TFS-Gel was then tested in the mice model of schizophrenia induced by ketamine by evaluating various behavioral parameters. The optimized formulation showed the particle size of 72.12 ± 0.72 nm, the PdI of 0.19 ± 0.07, the zeta potential of -55.56 ± 1.9 mV, the EE of 97.06 ± 0.10%, and the RE of 70.84 ± 1.54%. The in-vivo results showed that compared with the other treatment groups, there was a considerable increase in swimming and climbing time and a decrease in locomotors activity and immobility time in the group receiving APZ-TFS-Gel. Thus, APZ-TFS-Gel was found to have desirable characteristics for therapeutic improvement.

Preparation and characterization of itraconazole loaded nanomicelles based on dextran-behenic acid for cutaneous leishmaniasis treatment.

Cutaneous leishmaniasis is known as the most prevalent clinical form of leishmaniasis. It needs the development of new therapies due to the serious side-effects promoted by taking the current drugs. In the present study, dextran-behenic acid (DEX-BA) based nanomicelles were developed to direct the delivery of itraconazole (ITZ) to the macrophages and enhance its toxic effects against Leishmania parasites. DEX-BA was synthesized through the esterification of dextran with behenic acid. The critical micelle concentration of the newly developed conjugate was evaluated using pyrene as the fluorescent probe. The nanomicelles were generated by the dialysis method; then they were optimized by applying a Box-Behnken design. The effects of the dialysis temperature, polymer content, and sonication time on the characteristics of micelles were subsequently studied. Furthermore, in vitro efficacy against Leishmania major promastigotes and parasite-infected macrophages was evaluated. The optimized formulation showed the particle size of 195.16 ± 3.06 nm, the polydispersity index of 0.39 ± 0.01, the zeta potential of -16.29 ± 0.89 mV, the encapsulation efficiency % of 56.11 ± 4.9, and the release efficiency % of 51.29 ± 1.97. According to scanning electron microscopy, the nanomicelles were found to be nearly spherical in shape. ITZ-loaded nanomicelles showed the strongest anti-leishmanial activities when compared with the free ITZ and drug-free nanomicelles. It could be, therefore, concluded that ITZ-loaded nanomicelles might be useful as an alternative therapy for the treatment of cutaneous leishmania.

Simvastatin nanosuspensions prepared using a combination of pH-sensitive and timed-release approaches for potential treatment of colorectal cancer.

A dual pH- and time-dependent polymeric coated capsule was developed to achieve the site specificity of simvastatin (SIM) release in the colon. To improve the SIM solubility, soluplus-based nanosuspension of the drug were prepared by applying the anti-solvent crystallization technique; this was then followed by lyophilization. Particle size, polydispersity index, and saturation solubility were evaluated. The optimized nanosuspension was combined with SLS and freeze-dried before filling into hard gelatin capsules. Drug release characteristics of the coated capsules were studied in HCl 0.1 N, the phosphate buffers 6.8 and 7.4, and the simulated colonic fluid (pH 6.8). The in-vitro cytotoxic effects of SIM nanoparticles against HT29 cells were then evaluated using the MTT assay. The prepared nanoparticles were spherical with a mean size of 261.66 nm, the zeta potential of -18.20 and the dissolution efficiency of 59.71%. X-ray diffraction and differential scanning calorimetry studies showed that the nanosizing technique transformed the crystalline drug into the more soluble amorphous form. The coated capsules had no release in the gastric media, providing the specific delivery of SIM in the colon. The cytotoxic effect of the SIM nanoparticles was significantly increased, as compared to the free SIM. The findings, therefore, showed that the coated capsules using the two polymers of ethyl cellulose and Eudragit S100 could be suitable for the colon target delivery of SIM.

Preparation and Evaluation of Imatinib Loaded Transfersomal gel for the Treatment of Rheumatoid Arthritis.

In the present study, imatinib-loaded transfersomal gel (imatinib-TFS-Gel) was developed to minimize the oral dosing frequency and side effects during rheumatoid arthritis (RA) therapy. Imatinib-loaded transfersomes (imatinib-TFS) were prepared by the film-hydration method. The effects of lecithin content, lecithin/ EA ratio, and the type of EA on the characteristics of the imatinib-TFS were studied using a D-optimal design. Morphology of imatinib-TFS was investigated using scanning electron microscopy. The optimized imatinib-TFS formulation was used to prepare imatinib-TFS-Gel with the aid of Carbopol 940 as the gelling agent. The Optimized imatinib-TFS had a spherical shape with the particle size of 140.53 ± 0.87 nm, polydispersity index of 0.44 ± 0.01, the zeta potential of -17.63 ± 0.65 mV, encapsulation efficiency of 98.70 ± 0.38%, and release efficiency of 81.26 ± 0.70 %. Ex-vivo skin permeation studies through the rat skin showed that the cumulative amount of imatinib permeated from imatinib-TFS-Gel was significantly higher than that from imatinib-Gel. The RA rat model indicated a substantial reduction in paw edema during the 14 days study following the application of imatinib-TFS-Gel as compared with imatinib-Gel. Therefore, imatinib-TFS-Gel can be considered as a promising drug delivery system for the treatment of RA.

Preparation and evaluation of inhalable dry powder containing glucosamine-conjugated gefitinib SLNs for lung cancer therapy.

Gefitinib as an epidermal growth factor receptor tyrosine kinase inhibitor has strong potential in lung cancer therapy. However, a major challenge of using gefitinib is its toxicities. In the present study, we developed a dry powder inhaler dosage form containing gefitinib loaded glucosamine targeted solid lipid nanopaticles (Gef-G-SLNs) to locally transfer anticancer agent to the lung tumor. The Gef-G-SLNs were prepared by emulsion-solvent diffusion and evaporation method and optimized with irregular factorial design. The optimized nanoformulation was tested for action against A549 cells. Mannitol or lactose based dry powders were obtained from Gef-G-SLNs after spray drying and characterized using Anderson Cascade Impactor. The optimized formulation had drug loading of 33.29%, encapsulation efficiency of 97.31 ± 0.23%, zeta potential of -15.53 ± 0.47 mV, particle size of 187.23 ± 14.08 nm, polydispersity index of 0.28 ± 0.02 and release efficiency of 35.46 ± 2.25%. The Gef-G-SLNs showed superior anticancer effect compared to free gefitinib. The increased cellular uptake of G-SLNs in A549 cells was demonstrated compared with non-targeted SLNs using flow cytometry and fluorescence microscopy. The produced mannitol based microparticles showed suitable aerodynamic properties with an acceptable mass median aerodynamic diameter of 4.48 µm and fine particle fraction of 44.41%. Therefore, it can be concluded that this formulation represents promising drug delivery to treatment of lung cancer.

Encapsulation of Imatinib in Targeted KIT-5 Nanoparticles for Reducing its Cardiotoxicity and Hepatotoxicity.

BACKGROUND: Using imatinib, a tyrosine kinase inhibitor drug used in lymphoblastic leukemia, has always had limitations due to its cardiotoxicity and hepatotoxicity side effects. The objective of this study is to develop a target-oriented drug carrier to minimize these adverse effects by the controlled release of the drug. METHODS: KIT-5 nanoparticles were functionalized with 3-aminopropyltriethoxysilane and conjugated to rituximab as the targeting agent for the CD20 positive receptors of the B-cells. Then they were loaded with imatinib and their physical properties were characterized. The cell cytotoxicity of the nanoparticles was studied by MTT assay in Ramos (CD20 positive) and Jurkat cell lines (CD20 negative) and their cellular uptake was shown by fluorescence microscope. Wistar rats received an intraperitoneal injection of 50 mg/kg of the free drug or targeted nanoparticles for 21 days. Then the level of aspartate Aminotransferase (AST), alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) were measured in serum of animals. The cardiotoxicity and hepatotoxicity of the drug were also studied by hematoxylin and eosin staining of the tissues. RESULTS: The targeted nanoparticles of imatinib showed to be more cytotoxic to Ramos cells rather than Jurkat cells. The results of the biochemical analysis displayed a significant reduction in AST, ALT, ALP, and LDH levels in animals treated with targeted nanoparticles, compared to the free drug group. By comparison with the free imatinib, histopathological results represented less cardiotoxicity and hepatotoxicity in the animals, which received the drug through the current designed delivery system. CONCLUSION: The obtained results confirmed that the rituximab targeted KIT-5 nanoparticles are promising in the controlled release of imatinib and could decrease its cardiotoxicity and hepatotoxicity side effects.

In-vitro and in-vivo evaluation of chitosan-based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus.

The objective of this study was to develop an in-situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose-to-brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in-situ gels containing LZM-NLCs were prepared using a combination of chitosan and ß-glycerol phosphate (ß-GP). The anticonvulsant efficacy of LZM-NLCs-Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of -20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) ß-GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in-vivo findings showed that compared with the control group and the group that received LZM-Gel, the occurrence of PTZ-induced seizures in the rats was significantly reduced by LZM-NLCs-Gel after intranasal administration. These results, therefore, suggested that the LZM-NLCs-Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.

Carboxymethyl cellulose-based wafer enriched with resveratrol-loaded nanoparticles for enhanced wound healing.

The present study aimed to prepare and investigate the wound healing potential of carboxymethyl cellulose (CMC)-based wafers incorporated with resveratrol (RSV)-loaded cellulose acetate butyrate (CAB) NPs. Accordingly, RSV-CAB NPs were prepared using the solvent evaporation method. The effect of different formulation parameters (polymer content, surfactant concentration, and the volume ratio of aqueous phase to organic phase) on the properties of NPs was investigated using the Box-Behnken design. Then, the optimized NPs were incorporated in wafers comprising CMC combined with hydroxyl propyl methyl cellulose (HPMC) or chitosan. Hydration capacity, porosity, adhesive strength, and hardness of the prepared nanocomposite wafers were examined. Optimized formulation was spherical, showing the particle size, polydispersity index, zeta potential, encapsulation efficiency %, drug loading %, and release efficiency % of 248.5 nm, 0.38, - 1.59, 87.58, 25.94, and 67.10, respectively. The CMC-HPMC wafers exhibited higher porosity, hydration capacity, and adhesive performance, as compared with the CMC wafers alone and CMC-chitosan wafers. Wound healing test and histological evaluation in the excisional wounds of the rats showed that the RSV-NPs-wafers were more effective as a healing accelerator, in comparison to wafers without drug or those containing the free RSV. These results demonstrated the potential of the RSV-NPs-wafer in wound healing drug delivery applications. Graphical abstract.

Covalent polybenzimidazole-based triazine frameworks: A robust carrier for non-steroidal anti-inflammatory drugs.

Covalent triazine-based polymers (CTPs) are a new class of porous materials that can be used for the intercalation of therapeutic agents. The main purposes of designing new drug carriers include protecting them from degradation, enhancing their poor aqueous solubility, and investigating their controlled release properties. In this context, a novel polybenzimidazole-based CTP (BZ-CTP) was prepared by a solvothermal reaction between 4,4',4″-((1,3,5-triazine-2,4,6-triyl) tris(azanediyl)) tribenzoic acid (TCA) and 3,3'-diaminobenzidine. Piroxicam (PRX) and mefenamic acid (MFA) were loaded thoroughly into the CTP by using ultrasonication to form MFA-loaded CTP (MFA@BZ-CTP) and PRX-loaded CTP (PRX@BZ-CTP) with drug loading efficiencies of 49% and 53%, respectively. We attribute the increased loading efficiencies to the formation of π-π stacking forces between the aromatic rings present in the CTP structure and drugs. The in vitro release experiments were assessed in simulated physiological conditions using the dialysis method. Moreover, the release mechanisms were evaluated by Korsmeyer-Peppas kinetic studies and the obtained results showed excellent sustained releases of 81% after 96 h and 87% after 24 h for the PRX@BZ-CTP and MFA@BZ-CTP hybrids, respectively.

Synthesis of pectin-deoxycholic acid conjugate for targeted delivery of anticancer drugs in hepatocellular carcinoma.

Sorafenib (SF) a chemotherapeutic drug is used in hepatocellular carcinoma (HCC) with vast side effects. The aim of the project ahead was synthesis of SF loaded co-polymeric micelles of pectin-deoxycholic acid (P-DOCA) to target the overexpressed asialoglycoprotein receptors of hepatocytes by pectin. DOCA was modified with ethylenediamine and conjugated to pectin. FT-IR and 1HNMR confirmed the bio-conjugation. Pyrene was used to measure critical micelle concentration (CMC) by fluorimetry technique. P-DOCA micelles were loaded with SF and their particle size, zeta potential, drug loading and release efficiency were measured. MTT assay was used for determining cytotoxicity. The cell cycle arrest was studied by flow cytometry analysis and the cellular uptake was studied using cumarin-6 as the fluorophore agent. The micelles capability in preventing the cells migration was tested by Transwell plates. The CMC of P-DOCA micelles was 10.747 µg/mL. The best formulation obtained from SF to polymer ratio of 1:2. SF loaded micelles showed 30% increased cytotoxicity. The micelles cellular uptake was more than the free drug. Relative migration of HepG2 cells treated with SF loaded micelles was reduced to 6.67% compared to free SF which was 26.67%. The designed micelles are promising for antitumor drug targeting to HCC.