Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2016
The aim of this study was to develop and optimize deformable liposome for topical delivery of tre... more The aim of this study was to develop and optimize deformable liposome for topical delivery of tretinoin. Liposomal formulations were designed based on the full factorial design and prepared by fusion method. The influence of different ratio of soy phosphatidylcholine and transcutol (independent variables) on incorporation efficiency and drug release in 15 min and 24 h (responses) from liposomal formulations was evaluated. Liposomes were characterized for their vesicle size and Differential Scanning Calorimetry (DSC) was used to investigate changes in their thermal behavior. The penetration and retention of drug was determined using mouse skin. Also skin histology study was performed. Particle size of all formulations was smaller than 20 nm. Incorporation efficiency of liposomes was 79-93 %. Formulation F7 (25:5) showed maximum drug release. Optimum formulations were selected based on the contour plots resulted by statistical equations of drug release in 15 min and 24 h. Solubility p...
Jundishapur journal of natural pharmaceutical products, 2014
Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is us... more Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is usually associated with the drugs accumulation in renal tissue. Paromomycin sulfate (PMS) is an anti-leishmania drug. Although the topical approach for the treatment of leishmania is attractive, its use might cause nephrotoxicity and hepatotoxicity. This study aimed to evaluate probable nephrotoxicity and hepatotoxicity of topically administered PMS liposomes. Nine groups of male rats were used in this study; each group consisted of 6 rats that were evaluated in 3 time periods of 10, 20, and 30 days. Three groups were placed in each time period; a control group did not receive any medicine; a negative control group received liposome without paromomycin sulfate; and a positive control group received nanoliposomal formulations containing paromomycin sulfate. Pharmaceutical formulation (topical form) was used 2 times a day in a 12-hour interval. At the end of the period, hepatic enzymes (ALT,...
Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it has a short res... more Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it has a short residence time in the eye. The aim of this study is to develop ocular dorzolamide HCl nanoliposomes (DRZ – nanoliposomes) and to evaluate their potential use for the treatment of ocular hypertension. Nanoliposomes were prepared using Reverse-phase evaporation vesicle (REV) and thin layer hydration (TLH) method with 7:3 and 7:4 molar ratios of phosphatidy lcholine:cholesterol. The physicochemical properties of the formulations were investigated. Formulations with 7:4 lipid ratios were evaluated in terms of drug release, physical stability and ex-vivo permeation through the excised albino rabbit cornea. The rabbits in groups of 6 were treated with selected DRZ – nanoliposomes or dorzolamide solution or marketed dorzolamid preparation (Biosopt®) and intraocular pressure (IOP) was monitored. Formulations with 7:4 molar ratio entrapped greater amount of drug compared to those with 7:3 lipid components ratio. DRZ – nanoliposomes with 7:4 lipid ratio showed more transcorneal permeation than Dorzolamide solution (p<0.05); and the formulation prepared by TLH method exhibited higher permeability than that prepared by REV method (p<0.05). The selected DRZ – nanoliposomes showed greater IOP lowering activity and a more prolonged effect compared to dorzolamide solution and Biosopt®. DRZ – nanoliposomes prepared by TLH method with 7:4 ratios showed promising results as a candidate for the treatment of ocular hypertension.
Background: The aim of this study was to develop and optimize deformable liposome for topical del... more Background: The aim of this study was to develop and optimize deformable liposome for topical delivery of tretinoin. Methods: Liposomal formulations were designed based on the full factorial design and prepared by fusion method. The influence of different ratio of soy phosphatidylcholine and transcutol (independent variables) on incorporation efficiency and drug release in 15 min and 24 h (responses) from liposomal formulations was evaluated. Liposomes were characterized for their vesicle size and Differential Scanning Calorimetry (DSC) was used to investigate changes in their thermal behavior. The penetration and retention of drug was determined using mouse skin. Also skin histology study was performed. Results: Particle size of all formulations was smaller than 20 nm. Incorporation efficiency of liposomes was 79–93 %. Formulation F7 (25:5) showed maximum drug release. Optimum formulations were selected based on the contour plots resulted by statistical equations of drug release in 15 min and 24 h. Solubility properties of transcutol led to higher skin penetration for optimum formulations compared to tretinoin cream. There was no significant difference between the amount of drug retained in the skin by applying optimum formulations and cream. Histopatological investigation suggested optimum formulations could decrease the adverse effect of tretinoin in liposome compared to conventional cream.
Jundishapur journal of natural pharmaceutical products, 2014
Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is us... more Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is usually associated with the drugs accumulation in renal tissue. Paromomycin sulfate (PMS) is an anti-leishmania drug. Although the topical approach for the treatment of leishmania is attractive, its use might cause nephrotoxicity and hepatotoxicity. This study aimed to evaluate probable nephrotoxicity and hepatotoxicity of topically administered PMS liposomes. Nine groups of male rats were used in this study; each group consisted of 6 rats that were evaluated in 3 time periods of 10, 20, and 30 days. Three groups were placed in each time period; a control group did not receive any medicine; a negative control group received liposome without paromomycin sulfate; and a positive control group received nanoliposomal formulations containing paromomycin sulfate. Pharmaceutical formulation (topical form) was used 2 times a day in a 12-hour interval. At the end of the period, hepatic enzymes (ALT,...
The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomyci... more The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 g/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 g/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.
Messenger RNA encoding luciferase (mLUC) was complexed to the cationic lipids Lipofectamine or DO... more Messenger RNA encoding luciferase (mLUC) was complexed to the cationic lipids Lipofectamine or DOTAP/ DOPE, and to the cationic polymer linear poly(ethyleneimine) (linPEI). The complexes were incubated with HeLa cells and luciferase expression was assessed. The type of non-viral carrier used determined the extent and duration of protein expression. Maximal duration of mRNA expression was about 9 days for Lipofectamine complexes, i.e. not very much shorter than with pDNA polyplexes. Interestingly, luciferase activity was already detected 30 min after adding the mRNA complexes to the cells, independent on the type of carrier. We also assessed the proportion of cells that become transfected by means of transfection with an mRNA encoding GFP. For both cationic lipids transfection with mRNA yielded a substantially larger fraction of transfected cells (more than 80%) than transfection with pDNA (40%). In addition we tested the carriers for their ability to mediate delivery of mRNA encoding CXCR4 into mesenchymal stem cells. The fraction of CXCR4-positive cells obtained with the mRNA-cationic lipid complexes was around 80%, as compared to 40% for the linPEI polyplexes. Our results demonstrate that the advantage of the use of mRNA over that of pDNA may under certain conditions outweigh the disadvantage of the somewhat shorter expression period.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2016
The aim of this study was to develop and optimize deformable liposome for topical delivery of tre... more The aim of this study was to develop and optimize deformable liposome for topical delivery of tretinoin. Liposomal formulations were designed based on the full factorial design and prepared by fusion method. The influence of different ratio of soy phosphatidylcholine and transcutol (independent variables) on incorporation efficiency and drug release in 15 min and 24 h (responses) from liposomal formulations was evaluated. Liposomes were characterized for their vesicle size and Differential Scanning Calorimetry (DSC) was used to investigate changes in their thermal behavior. The penetration and retention of drug was determined using mouse skin. Also skin histology study was performed. Particle size of all formulations was smaller than 20 nm. Incorporation efficiency of liposomes was 79-93 %. Formulation F7 (25:5) showed maximum drug release. Optimum formulations were selected based on the contour plots resulted by statistical equations of drug release in 15 min and 24 h. Solubility p...
Jundishapur journal of natural pharmaceutical products, 2014
Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is us... more Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is usually associated with the drugs accumulation in renal tissue. Paromomycin sulfate (PMS) is an anti-leishmania drug. Although the topical approach for the treatment of leishmania is attractive, its use might cause nephrotoxicity and hepatotoxicity. This study aimed to evaluate probable nephrotoxicity and hepatotoxicity of topically administered PMS liposomes. Nine groups of male rats were used in this study; each group consisted of 6 rats that were evaluated in 3 time periods of 10, 20, and 30 days. Three groups were placed in each time period; a control group did not receive any medicine; a negative control group received liposome without paromomycin sulfate; and a positive control group received nanoliposomal formulations containing paromomycin sulfate. Pharmaceutical formulation (topical form) was used 2 times a day in a 12-hour interval. At the end of the period, hepatic enzymes (ALT,...
Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it has a short res... more Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it has a short residence time in the eye. The aim of this study is to develop ocular dorzolamide HCl nanoliposomes (DRZ – nanoliposomes) and to evaluate their potential use for the treatment of ocular hypertension. Nanoliposomes were prepared using Reverse-phase evaporation vesicle (REV) and thin layer hydration (TLH) method with 7:3 and 7:4 molar ratios of phosphatidy lcholine:cholesterol. The physicochemical properties of the formulations were investigated. Formulations with 7:4 lipid ratios were evaluated in terms of drug release, physical stability and ex-vivo permeation through the excised albino rabbit cornea. The rabbits in groups of 6 were treated with selected DRZ – nanoliposomes or dorzolamide solution or marketed dorzolamid preparation (Biosopt®) and intraocular pressure (IOP) was monitored. Formulations with 7:4 molar ratio entrapped greater amount of drug compared to those with 7:3 lipid components ratio. DRZ – nanoliposomes with 7:4 lipid ratio showed more transcorneal permeation than Dorzolamide solution (p<0.05); and the formulation prepared by TLH method exhibited higher permeability than that prepared by REV method (p<0.05). The selected DRZ – nanoliposomes showed greater IOP lowering activity and a more prolonged effect compared to dorzolamide solution and Biosopt®. DRZ – nanoliposomes prepared by TLH method with 7:4 ratios showed promising results as a candidate for the treatment of ocular hypertension.
Background: The aim of this study was to develop and optimize deformable liposome for topical del... more Background: The aim of this study was to develop and optimize deformable liposome for topical delivery of tretinoin. Methods: Liposomal formulations were designed based on the full factorial design and prepared by fusion method. The influence of different ratio of soy phosphatidylcholine and transcutol (independent variables) on incorporation efficiency and drug release in 15 min and 24 h (responses) from liposomal formulations was evaluated. Liposomes were characterized for their vesicle size and Differential Scanning Calorimetry (DSC) was used to investigate changes in their thermal behavior. The penetration and retention of drug was determined using mouse skin. Also skin histology study was performed. Results: Particle size of all formulations was smaller than 20 nm. Incorporation efficiency of liposomes was 79–93 %. Formulation F7 (25:5) showed maximum drug release. Optimum formulations were selected based on the contour plots resulted by statistical equations of drug release in 15 min and 24 h. Solubility properties of transcutol led to higher skin penetration for optimum formulations compared to tretinoin cream. There was no significant difference between the amount of drug retained in the skin by applying optimum formulations and cream. Histopatological investigation suggested optimum formulations could decrease the adverse effect of tretinoin in liposome compared to conventional cream.
Jundishapur journal of natural pharmaceutical products, 2014
Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is us... more Hepatotoxicity due to drugs is the most common cause of deaths. Nephrotoxicity of the drugs is usually associated with the drugs accumulation in renal tissue. Paromomycin sulfate (PMS) is an anti-leishmania drug. Although the topical approach for the treatment of leishmania is attractive, its use might cause nephrotoxicity and hepatotoxicity. This study aimed to evaluate probable nephrotoxicity and hepatotoxicity of topically administered PMS liposomes. Nine groups of male rats were used in this study; each group consisted of 6 rats that were evaluated in 3 time periods of 10, 20, and 30 days. Three groups were placed in each time period; a control group did not receive any medicine; a negative control group received liposome without paromomycin sulfate; and a positive control group received nanoliposomal formulations containing paromomycin sulfate. Pharmaceutical formulation (topical form) was used 2 times a day in a 12-hour interval. At the end of the period, hepatic enzymes (ALT,...
The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomyci... more The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 g/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 g/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.
Messenger RNA encoding luciferase (mLUC) was complexed to the cationic lipids Lipofectamine or DO... more Messenger RNA encoding luciferase (mLUC) was complexed to the cationic lipids Lipofectamine or DOTAP/ DOPE, and to the cationic polymer linear poly(ethyleneimine) (linPEI). The complexes were incubated with HeLa cells and luciferase expression was assessed. The type of non-viral carrier used determined the extent and duration of protein expression. Maximal duration of mRNA expression was about 9 days for Lipofectamine complexes, i.e. not very much shorter than with pDNA polyplexes. Interestingly, luciferase activity was already detected 30 min after adding the mRNA complexes to the cells, independent on the type of carrier. We also assessed the proportion of cells that become transfected by means of transfection with an mRNA encoding GFP. For both cationic lipids transfection with mRNA yielded a substantially larger fraction of transfected cells (more than 80%) than transfection with pDNA (40%). In addition we tested the carriers for their ability to mediate delivery of mRNA encoding CXCR4 into mesenchymal stem cells. The fraction of CXCR4-positive cells obtained with the mRNA-cationic lipid complexes was around 80%, as compared to 40% for the linPEI polyplexes. Our results demonstrate that the advantage of the use of mRNA over that of pDNA may under certain conditions outweigh the disadvantage of the somewhat shorter expression period.
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Papers by Neda Bavarsad