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1.
Pharm Dev Technol ; 27(3): 301-312, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35238273

ABSTRACT

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.


Subject(s)
Insulin , Phenytoin , Bandages , Hypromellose Derivatives , Micelles , Phenytoin/chemistry , Polymers/chemistry , Water/chemistry
2.
Drug Dev Ind Pharm ; 47(3): 416-428, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33617377

ABSTRACT

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.


Subject(s)
Itraconazole , Leishmaniasis, Cutaneous , Dextrans , Fatty Acids , Humans , Leishmaniasis, Cutaneous/drug therapy , Micelles
3.
Pharm Dev Technol ; 26(3): 335-348, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33430677

ABSTRACT

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.


Subject(s)
Anticholesteremic Agents/administration & dosage , Antineoplastic Agents/administration & dosage , Delayed-Action Preparations/chemistry , Simvastatin/administration & dosage , Anticholesteremic Agents/chemistry , Anticholesteremic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Colorectal Neoplasms/drug therapy , Drug Liberation , HT29 Cells , Humans , Hydrogen-Ion Concentration , Simvastatin/chemistry , Simvastatin/pharmacology
4.
Pharm Dev Technol ; 26(8): 867-879, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34193009

ABSTRACT

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.


Subject(s)
Antipsychotic Agents/administration & dosage , Aripiprazole/administration & dosage , Nanogels/administration & dosage , Administration, Intranasal , Animals , Disease Models, Animal , Humans , Male , Mice , Motor Activity/drug effects , Nanoparticle Drug Delivery System/administration & dosage , Particle Size , Schizophrenia/drug therapy , Spectroscopy, Fourier Transform Infrared
5.
Drug Dev Ind Pharm ; 46(8): 1265-1277, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32594775

ABSTRACT

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.


Subject(s)
Gefitinib/therapeutic use , Glucosamine/administration & dosage , Lung Neoplasms , Nanoparticles , Administration, Inhalation , Dry Powder Inhalers , Gefitinib/chemistry , Glucosamine/chemistry , Humans , Lung Neoplasms/drug therapy , Particle Size , Powders
6.
Pharm Dev Technol ; 24(7): 891-901, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31062987

ABSTRACT

This study was conducted to develop an in situ thermosensitive gel containing sertaconazole-loaded nanostructured lipid carriers (NLCs) for prolonged ocular drug delivery. To this end, sertaconazole-loaded NLCs (sertaconazole-NLCs) were prepared by emulsification solvent-diffusion method and the effects of different formulation variables were assessed using the fractional factorial design. Then, optimized sertaconazole-NLCs were incorporated into the pluronic F127 (PF127)/hydroxy propylmethylcellulose (HPMC) K4M hydrogel. The formulations were examined for pH, gelation temperature, rheological properties, in vitro permeation studies, and anti-fungal activity. The optimized sertaconazole-NLCs showed a mean particle size of 272.40 nm, encapsulation efficiency of 89.97%, zeta potential of 12.9 mV, and polydispersity index of 0.31. All the in situ formulations had acceptable pH, ranging from 5.89 to 6.28. The gelation temperature of the optimized formulation was 35.1 °C after dilution with simulated tear fluid (STF). Sertaconazole-NLCs showed a higher antifungal activity and permeation through the bovine cornea compared to the free drug and the in situ gel formulation. The cornea penetration of sertaconazole for the in situ gel of NLCs was also comparable to that for free drug. The obtained results indicated that the prepared nanocomposite system may have potential for treatment of fungal keratitis.


Subject(s)
Antifungal Agents/administration & dosage , Drug Carriers/chemistry , Imidazoles/administration & dosage , Lipids/chemistry , Nanoparticles/chemistry , Thiophenes/administration & dosage , Animals , Antifungal Agents/pharmacokinetics , Antifungal Agents/pharmacology , Candida albicans/drug effects , Candidiasis/drug therapy , Cattle , Cornea/metabolism , Drug Liberation , Hydrogels/chemistry , Imidazoles/pharmacokinetics , Imidazoles/pharmacology , Keratitis/drug therapy , Nanoparticles/ultrastructure , Poloxamer/chemistry , Temperature , Thiophenes/pharmacokinetics , Thiophenes/pharmacology
7.
Drug Dev Ind Pharm ; 44(2): 276-288, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29043860

ABSTRACT

The aim of this study was to develop hydroxypropyl methyl cellulose (HPMC)/chitosan gel containing polymeric micelles loaded with simvastatin (Sim) and evaluates its wound healing properties in rats. An irregular full factorial design was employed to evaluate the effects of various formulation variables including polymer/drug ratio, hydration temperature, hydration time, and organic solvent type on the physicochemical characteristics of pluronic F127-cholesterol nanomicelles prepared using the film hydration method. Among single studied factors, solvent type had the most impact on the amount of drug loading and zeta potential. Particle size and release efficiency was more affected by hydration temperature. The optimized formulation suggested by desirability of 93.5% was prepared using 1 mg of Sim, 10 mg of copolymer, dichloromethane as the organic solvent, hydration time of 45 min and hydration temperature of 25 °C. The release of the drug from nanomicelles was found to be biphasic and showed a rapid release in the first stage followed by a sustained release for 96 h. The gel-contained nanomicelles exhibited pseudo-plastic flow and more sustained drug release profile compared to nanomicelles. In excision wound model on normal rats, the wound closure of the group treated by Sim loaded micelles-gel was superior to other groups. Taken together, Sim loaded micelles-gel may represent a novel topical formulation for wound healing.


Subject(s)
Chitosan/chemistry , Hypromellose Derivatives/chemistry , Micelles , Simvastatin/administration & dosage , Simvastatin/pharmacology , Wound Healing/drug effects , Animals , Chemistry, Pharmaceutical , Cholesterol/chemistry , Drug Carriers/chemistry , Drug Liberation , Gels , Male , Nanoparticles/chemistry , Particle Size , Poloxamer/chemistry , Polyethylene Glycols/chemistry , Rats , Rats, Wistar , Rheology , Simvastatin/pharmacokinetics , Surface Properties
8.
J Liposome Res ; 25(2): 157-65, 2015.
Article in English | MEDLINE | ID: mdl-25275925

ABSTRACT

The objective of the present study was to prepare a micellar polymeric carrier for the delivery of Docetaxel (DTX) as a kind of polysorbate free preparation. Pluronic F127 (PF127) was conjugated to cholesterol (Chol) via succinyl linkage and characterized by FTIR and HNMR. DTX-loaded polymeric micelles were prepared via film hydration method. Physicochemical properties of micelles including particle size, zeta potential, drug loading and release efficiency were studied. The critical micelle concentration (CMC) was determined using pyrene as a hydrophobic fluorescent probe. In vitro cytotoxicity of micelles was evaluated in B16F10 melanoma cells and HepG2 cell line. The FTIR and HNMR spectroscopy methods confirmed the conjugation of PF127 to cholesterol via succinyl linkage. The micelles were spherical under scanning electron microscope (SEM) with the mean particle size of 248.2 ± 8-278.8 ± 12.3 nm and zeta potential ranging from -17.2 ± 8.7 to -28.4 ± 12.7 mV. Drug loading efficiency was higher than 98%. The in vitro release study showed the sustained release behavior of DTX within 144 h. The CMC of the micelles was about 41.67 ± 0.17 µg/ml, which was significantly lower than the CMC of pure PF127 micelles. Compared with the free drug, DTX-loaded micelles showed higher cytotoxicity against B16F10 melanoma and HepG2 cell lines.


Subject(s)
Cholesterol/chemistry , Drug Delivery Systems , Melanoma/metabolism , Micelles , Taxoids/administration & dosage , Taxoids/pharmacology , Cell Survival/drug effects , Docetaxel , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , Structure-Activity Relationship , Taxoids/chemistry
9.
Res Pharm Sci ; 18(5): 528-540, 2023.
Article in English | MEDLINE | ID: mdl-37842521

ABSTRACT

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.

10.
Res Pharm Sci ; 18(1): 49-58, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36846738

ABSTRACT

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.

11.
J Biomater Appl ; 38(4): 509-526, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37632164

ABSTRACT

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.


Subject(s)
Chemical and Drug Induced Liver Injury , Liposomes , Mice , Animals , Liposomes/chemistry , Flavonoids/therapeutic use , Antioxidants/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/prevention & control
12.
Drug Deliv Transl Res ; 13(3): 862-882, 2023 03.
Article in English | MEDLINE | ID: mdl-36223030

ABSTRACT

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.


Subject(s)
Leishmaniasis, Cutaneous , Nanofibers , Mice , Animals , Sorafenib , Leishmaniasis, Cutaneous/drug therapy , Polymers/therapeutic use
13.
J Biomater Appl ; 37(5): 859-871, 2022 11.
Article in English | MEDLINE | ID: mdl-35999010

ABSTRACT

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.


Subject(s)
Colitis, Ulcerative , Nanoparticles , Rats , Animals , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Simvastatin/therapeutic use , Simvastatin/chemistry , Nanoparticles/chemistry , Drug Delivery Systems/methods , Particle Size , Hydrogen-Ion Concentration , Drug Carriers/chemistry
14.
Int J Pharm ; 624: 122036, 2022 Aug 25.
Article in English | MEDLINE | ID: mdl-35868480

ABSTRACT

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.


Subject(s)
Chitosan , Nanoparticles , Neoplasms , Animals , Butyrates , Cellulose/analogs & derivatives , Drug Carriers , Gefitinib , Hydrogels , Mice , Particle Size
15.
Iran J Pharm Res ; 20(4): 33-46, 2021.
Article in English | MEDLINE | ID: mdl-35194426

ABSTRACT

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.

16.
J Biomater Sci Polym Ed ; 32(15): 1944-1965, 2021 10.
Article in English | MEDLINE | ID: mdl-34228587

ABSTRACT

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.


Subject(s)
Hesperidin , Nanofibers , Acrylic Resins , Bandages , Polyethylene Glycols
17.
IET Nanobiotechnol ; 14(2): 148-154, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32433032

ABSTRACT

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.


Subject(s)
Chitosan/chemistry , Gels/chemistry , Lorazepam/pharmacokinetics , Nanostructures/chemistry , Status Epilepticus/drug therapy , Administration, Intranasal , Animals , Gels/administration & dosage , Lipids/chemistry , Lorazepam/administration & dosage , Lorazepam/therapeutic use , Male , Nanostructures/administration & dosage , Particle Size , Rats , Rats, Wistar
18.
Mater Sci Eng C Mater Biol Appl ; 108: 110482, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31923971

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Benzimidazoles/chemistry , Drug Carriers/chemistry , Polymers/chemistry , Triazines/chemistry , Carbon Dioxide , Kinetics , Mefenamic Acid/chemistry , Nanoparticles/chemistry , Piroxicam/chemistry , Porosity , Solubility , Spectroscopy, Fourier Transform Infrared , Temperature , X-Ray Diffraction
19.
Drug Deliv Transl Res ; 10(5): 1241-1254, 2020 10.
Article in English | MEDLINE | ID: mdl-31981141

ABSTRACT

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.


Subject(s)
Carboxymethylcellulose Sodium , Chitosan , Nanoparticles , Wound Healing , Animals , Particle Size , Rats , Resveratrol
20.
Anticancer Agents Med Chem ; 20(16): 1966-1980, 2020.
Article in English | MEDLINE | ID: mdl-32560620

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/pharmacology , Imatinib Mesylate/pharmacology , Nanoparticles/chemistry , Protein Kinase Inhibitors/pharmacology , Rituximab/pharmacology , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemistry , Capsules , Cell Line , Cell Survival/drug effects , Dose-Response Relationship, Drug , Female , Heart/drug effects , Humans , Imatinib Mesylate/adverse effects , Imatinib Mesylate/chemistry , Liver/drug effects , Liver/pathology , Molecular Structure , Particle Size , Porosity , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/chemistry , Rats , Rats, Wistar , Rituximab/chemistry , Structure-Activity Relationship , Surface Properties
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