Sharareh Eskandari - Academia.edu (original) (raw)
Papers by Sharareh Eskandari
mBio, 2021
A vaccine to control S. pyogenes infection is desperately warranted. S. pyogenes colonizes the up... more A vaccine to control S. pyogenes infection is desperately warranted. S. pyogenes colonizes the upper respiratory tract (URT) and skin, from where it can progress to invasive and immune-mediated diseases.
Research in Pharmaceutical Sciences, 2009
The most frequent adverse effects of indomethacin like other NSAIDs are gastro–intestinal and cen... more The most frequent adverse effects of indomethacin like other NSAIDs are gastro–intestinal and central nervous system disturbances. Extended release or enteric release formulations minimize these symptoms. The objective of this study was to develop an extended release pellet formulation of indomethacin by the centrifugation (rotary fluid bed granulation) or powder layering method. Layered, nonpareil pellets composed of sugar, Avicel PH 101 and lactose were prepared using FREUND CFgranulator and were treated by a binder solution (HPC-L) applied by spray gun. A conical designed powder-feeding unit applied the drug powder. Drug content of pellets was determined by HPLC method. Eudragit NE 30 D was used for coating the prepared pellets. The results show that increasing the amount of Eudragit NE 30 D, Opadray and SDS in coating solution adjusts release of the pellets. The dissolution profile achieved from pellets containing 500 g nonpareil, 400 g indomethacin, 400 ml HPC 8%, 61g talc, 50 ...
There are more than 100 types of arthritis and its related conditions. The goal of arthritis trea... more There are more than 100 types of arthritis and its related conditions. The goal of arthritis treatment is to reduce joint pain and inflammation. In this regard, glucosamine is known to stop degenerative process of osteoarthritis. Topically applied products, compared with those taken orally, are safer and cause less complications. Various researches on different kinds of glucosamine showed that skin permeation of the topical dosage form improves pain scale more effectively in comparison with placebo after 6 weeks. The results have shown that transdermal glucosamine is more cost-effective than oral dosage form. Rahamin is an Iranian brand of transdermal glucosamine which contains Glucosamine, Devil's claw dry extract, MSM and vegetable oils.
Cell Host & Microbe
Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and a... more Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available. People most at risk of severe disease are the elderly, immunosuppressed, and asplenic individuals. B. microti and B. divergens are the predominant species affecting humans. Here, we present a whole-parasite Babesia vaccine. To establish proof-of-principle, we employed chemically attenuated B. microti parasitized red blood cells from infected mice. To aid clinical translation, we produced liposomes containing killed parasite material. Vaccination significantly reduces peak parasitemia following challenge. B cells and anti-parasite antibodies do not significantly contribute to vaccine efficacy. Protection is abrogated by the removal of CD4+ T cells or macrophages prior to challenge. Importantly, splenectomized mice are protected by vaccination. To further facilitate translation, we prepared a culture-based liposomal vaccine and demonstrate that this performs as a universal vaccine inducing immunity against different human Babesia species.
Methods in Molecular Biology
Clinical & Translational Immunology
Carbohydrate Polymers, 2012
Freeze-drying technique preserves the stability of nanoparticles. The objective of this study was... more Freeze-drying technique preserves the stability of nanoparticles. The objective of this study was optimization of freeze-drying condition of nano lipid carriers (NLCs). NLCs were prepared by emulsion-solvent evaporation followed by ultra-sonication method. Different carbohydrate and polymeric cryoprotectants including Microcelac ® (mixture of lactose and Avicel), Avicel PH102 (microcrystalline cellulose), mannitol, sucrose, Avicel RC591 (mixture of microcrystalline cellulose and sodium carboxymethyl cellulose), maltodextrine, Aerosil and PEG4000 were tested initially. The NLCs showing lower particle size growth and greater absolute zeta potential after freeze drying were chosen for further investigation using Taguchi optimization method. Studied factors included cryoprotectant type and concentration, freezing temperatures applied at different time periods and sublimation time. Sucrose, Avicel RC591 and Aerosil were selected as cryoprotectants from initial screening tests. Increasing their concentration increased the particle size. 1% of Avicel RC591, 24 h of freezing at −70 • C and 48 h sublimation time showed lower growth in particle size.
Chemistry (Weinheim an der Bergstrasse, Germany), Jan 11, 2018
Adjuvant development and understanding the physicochemical properties of particles and interpreti... more Adjuvant development and understanding the physicochemical properties of particles and interpreting the subsequent immunological responses is a challenge faced by many researchers in the vaccine field. We synthesized and investigated the physicochemical properties and immunogenicity of a library of multiple epitope self-adjuvant lipopeptides in a novel asymmetric arrangement. Vaccine candidates were synthesized using a combination of solid-phase peptide synthesis and copper-mediated click chemistry. In vivo studies showed that vaccine constructs containing a single OVA CD8 T-cell epitope and two N-terminally located C16 lipid moieties were more effective at generating robust cellular immune responses compared to the same molecule containing multiple copies of the OVA CD8 T-cell epitope with or without the C16 moieties. Furthermore, attachment of the two C16 lipids to the N-terminus provoked formation of long β-sheet fibrils and was shown to induce a higher CD8 donor T-cell frequency...
Advanced drug delivery reviews, Jan 26, 2016
Self-assembled peptides have shown outstanding characteristics for vaccine delivery and drug targ... more Self-assembled peptides have shown outstanding characteristics for vaccine delivery and drug targeting. Peptide molecules can be rationally designed to self-assemble into specific nanoarchitectures in response to changes in their assembly environment including: pH, temperature, ionic strength, and interactions between host (drug) and guest molecules. The resulting supramolecular nanostructures include nanovesicles, nanofibers, nanotubes, nanoribbons, and hydrogels and have a diverse range of mechanical and physicochemical properties. These molecules can be designed for cell-specific targeting by including adhesion ligands, receptor recognition ligands, or peptide-based antigens in their design, often in a multivalent display. Depending on their design, self-assembled peptide nanostructures have advantages in biocompatibility, stability against enzymatic degradation, encapsulation of hydrophobic drugs, sustained drug release, shear-thinning viscoelastic properties, and/or adjuvanting...
Bioorganic & Medicinal Chemistry, 2016
Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of ... more Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of which are fatal. Currently, our efforts to develop a vaccine against GAS focuses on the lipid core peptide (LCP) system, a subunit vaccine containing a lipoamino acid (LAA) moiety which allows the stimulation of systemic antibody activity. In the present study, a peptide (J14) representing the B-cell epitope from the GAS M protein was incorporated alongside a universal T-helper epitope (P25) in four LCP constructs of different spatial orientation or LAA lengths. Through structure-activity studies, it was discovered that while the alteration of the LCP orientation had a weaker effect on immunostimulation, increasing the LAA side chain length within the construct increased antibody responses in murine models. Furthermore, the mice immunised with the lead LCP construct were also able to maintain antibody activity throughout the course of five months. These findings highlight the importance of LAA moieties in the development of intranasal peptide vaccines and confirmed that its side chain length has an effect on the immunogenicity of the structure.
Bioconjugate chemistry, Jan 6, 2016
Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long bee... more Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognised as a frontline receptor in pathogen recognition. During the last decade many attempts have been made to target this receptor for applications including vaccine and drug development. In the present study, a library of vaccine constructs comprising fluorescently-labelled mannosylated lipid-dendrimers that contained the ovalbumin CD4+ epitope, OVA323-339, as the model peptide antigen were synthesised using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. Uptake studies performed on F4/80+ and CD11c+ cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the co...
Nanomedicine, 2015
Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features p... more Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features promoting strong CD8(+) T-cell responses. Three different self-adjuvanting lipid core peptide nanovaccines each comprising four copies of the dominant ovalbumin CD8(+) T-cell epitope and varying in the utilization of a polylysine or glucose core with 2-amino-hexadecanoic acid (C16) or 2-amino-dodecanoic acid (C12) lipids were synthesized. Vaccines were tested for ability to induce CD8(+) T-cell responses and inhibit tumor growth in vivo. The construct utilizing C12 lipids and polylysine core induced very robust effector T cells shown to have in vivo effector capability as demonstrated by in vivo cytotoxicity and ability to inhibit tumor growth as well as modulation of dendritic cell activation. The C12 polylysine platform was an effective configuration for induction of potent CD8(+) T-cell responses.
Chemistry - A European Journal, 2014
Designing a lipopeptide (LP) vaccine with a specific asymmetric arrangement of epitopes may resul... more Designing a lipopeptide (LP) vaccine with a specific asymmetric arrangement of epitopes may result in an improved display of antigens, increasing host-cell recognition and immunogenicity. This study aimed to synthesise and characterise the physicochemical properties of a library of asymmetric LP-based vaccine candidates that contained multiple CD4 + and CD8 + T-cell epitopes from the model protein antigen, ovalbumin. These fully synthetic vaccine candidates were prepared by microwave-assisted solid phase peptide synthesis. The C12 or C16 lipoamino acids were coupled to the N or C terminus of the OVA CD4 peptide epitope. The OVA CD4 LPs and OVA CD8 peptide constructs were then conjugated using azide-alkyne Huisgen cycloaddition to give multivalent synthetic vaccines. Physiochemical characterisation of these vaccines showed a tendency to self-assemble in aqueous media. Changes in lipid length and position induced self-assembly with significant changes to their morphology and secondary structure as shown by transmission electron microscopy and circular dichroism.
Aaps Pharmscitech, 2010
The aim of this study was to formulate and characterize Eudragit® L100 and Eudragit® L100-poly(la... more The aim of this study was to formulate and characterize Eudragit® L100 and Eudragit® L100-poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing diclofenac sodium. Diclofenac generates severe adverse effects with risks of toxicity. Thus, nanoparticles were prepared to reduce these drawbacks in the present study. These nanoparticles were evaluated for surface morphology, particle size and size distribution, percentage drug entrapment, and in vitro drug release in pH 6.8. The prepared nanoparticles were almost spherical in shape, as determined by atomic force microscopy. The nanoparticles with varied size (241–274 nm) and 25.8–62% of entrapment efficiency were obtained. The nanoparticles formulations produced the release profiles with an initial burst effect in which diclofenac sodium release ranged between 38% and 47% within 4 h. The extent of drug release from Eudragit® L100 nanoparticles was up to 92% at 12 h. However, Eudragit®/PLGA nanoparticles showed an initial burst release followed by a slower sustained release. The cumulative release at 72 h was 56%, 69%, and 81% for Eudragit®/PLGA (20:80), Eudragit®/PLGA (30:70) and Eudragit®/PLGA (50:50) nanoparticles, respectively. The release profiles and encapsulation efficiencies depended on the amount of Eudragit in the blend. These data demonstrated the efficacy of these nanoparticles in sustaining the diclofenac sodium release profile.
The objective of this study was to optimize a nano-lipid carrier (NLCs) of valproic acid for nasa... more The objective of this study was to optimize a nano-lipid carrier (NLCs) of valproic acid for nasal delivery using statistical methods. NLCs were prepared by solvent diffusion method followed by ultrasonication. After a preliminary screening study using Taguchi design, the Box-Behnken statistical model using desirability function was applied to evaluate variables affecting key specifications (minimum particle size, maximum drug loading and optimum release) of nano-lipid carriers of valproic acid. Each variable was assessed at three levels of surfactant concentration, acetone/ethanol volume ratio and organic/aqueous phase volume ratio. The best predicted model for particle size and drug release was quadratic model, while for drug loading, 2 factor interaction model fitted better. The measured results for the optimized formulation were a mean size of 154 nm, 47% payload and 75% of drug content released within 21 days. The optimum formulation was obtained using 1% of Poloxamer-188 as surfactant, organic/aqueous phase volume ratio of 1/5 and acetone/ethanol volume ratio of 3/1. Overall, the results show that entrapment of valproic acid in nano-lipid carriers was achieved. Such carriers might be a promising delivery system in the treatment of seizures via the nasal route of administration.
Three different formulations of a lipid-modified endomorphin-1 peptide (C 10 LAA-Endo-1) were pre... more Three different formulations of a lipid-modified endomorphin-1 peptide (C 10 LAA-Endo-1) were prepared, characterized, and evaluated for their permeability through Caco-2 cell membranes. Solid lipid nanoparticles (SLN), enteric coated (EC), and the EC-SLN of C 10 LAA-Endo-1 is a modified structure of endomorphin-1 for oral delivery. Physico-chemical characterization of the formulations showed that among all formulations, EC-[C 10 LAA-Endo-1] had the lowest particle size and the highest EE% and absolute zeta potential. Release of drug from SLN, EC-SLN and EC-[C 10 LAA-Endo-1] in acid media was 14.30 (AE2.7)%, 3.0 (AE1.0)% and 10.2 (AE3.0)%, respectively. Release data in buffer media (pH ¼ 7.4) showed that enteric coated formulations released C 10 LAA-Endo-1 more slowly than uncoated formulations. It was also demonstrated that direct coating of C 10 LAA-Endo-1 with Eudragit Õ S100 significantly enhanced the permeability of the compound through Caco-2 cell membranes with a 39-fold higher P app compared to C 10 LAA-Endo-1. These findings indicated that EC-C 10 LAA-Endo-1 is a promising candidate to promote the oral delivery of the previously modified endomorphin-1 peptide analogue and is worthy of future animal investigations.
mBio, 2021
A vaccine to control S. pyogenes infection is desperately warranted. S. pyogenes colonizes the up... more A vaccine to control S. pyogenes infection is desperately warranted. S. pyogenes colonizes the upper respiratory tract (URT) and skin, from where it can progress to invasive and immune-mediated diseases.
Research in Pharmaceutical Sciences, 2009
The most frequent adverse effects of indomethacin like other NSAIDs are gastro–intestinal and cen... more The most frequent adverse effects of indomethacin like other NSAIDs are gastro–intestinal and central nervous system disturbances. Extended release or enteric release formulations minimize these symptoms. The objective of this study was to develop an extended release pellet formulation of indomethacin by the centrifugation (rotary fluid bed granulation) or powder layering method. Layered, nonpareil pellets composed of sugar, Avicel PH 101 and lactose were prepared using FREUND CFgranulator and were treated by a binder solution (HPC-L) applied by spray gun. A conical designed powder-feeding unit applied the drug powder. Drug content of pellets was determined by HPLC method. Eudragit NE 30 D was used for coating the prepared pellets. The results show that increasing the amount of Eudragit NE 30 D, Opadray and SDS in coating solution adjusts release of the pellets. The dissolution profile achieved from pellets containing 500 g nonpareil, 400 g indomethacin, 400 ml HPC 8%, 61g talc, 50 ...
There are more than 100 types of arthritis and its related conditions. The goal of arthritis trea... more There are more than 100 types of arthritis and its related conditions. The goal of arthritis treatment is to reduce joint pain and inflammation. In this regard, glucosamine is known to stop degenerative process of osteoarthritis. Topically applied products, compared with those taken orally, are safer and cause less complications. Various researches on different kinds of glucosamine showed that skin permeation of the topical dosage form improves pain scale more effectively in comparison with placebo after 6 weeks. The results have shown that transdermal glucosamine is more cost-effective than oral dosage form. Rahamin is an Iranian brand of transdermal glucosamine which contains Glucosamine, Devil's claw dry extract, MSM and vegetable oils.
Cell Host & Microbe
Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and a... more Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available. People most at risk of severe disease are the elderly, immunosuppressed, and asplenic individuals. B. microti and B. divergens are the predominant species affecting humans. Here, we present a whole-parasite Babesia vaccine. To establish proof-of-principle, we employed chemically attenuated B. microti parasitized red blood cells from infected mice. To aid clinical translation, we produced liposomes containing killed parasite material. Vaccination significantly reduces peak parasitemia following challenge. B cells and anti-parasite antibodies do not significantly contribute to vaccine efficacy. Protection is abrogated by the removal of CD4+ T cells or macrophages prior to challenge. Importantly, splenectomized mice are protected by vaccination. To further facilitate translation, we prepared a culture-based liposomal vaccine and demonstrate that this performs as a universal vaccine inducing immunity against different human Babesia species.
Methods in Molecular Biology
Clinical & Translational Immunology
Carbohydrate Polymers, 2012
Freeze-drying technique preserves the stability of nanoparticles. The objective of this study was... more Freeze-drying technique preserves the stability of nanoparticles. The objective of this study was optimization of freeze-drying condition of nano lipid carriers (NLCs). NLCs were prepared by emulsion-solvent evaporation followed by ultra-sonication method. Different carbohydrate and polymeric cryoprotectants including Microcelac ® (mixture of lactose and Avicel), Avicel PH102 (microcrystalline cellulose), mannitol, sucrose, Avicel RC591 (mixture of microcrystalline cellulose and sodium carboxymethyl cellulose), maltodextrine, Aerosil and PEG4000 were tested initially. The NLCs showing lower particle size growth and greater absolute zeta potential after freeze drying were chosen for further investigation using Taguchi optimization method. Studied factors included cryoprotectant type and concentration, freezing temperatures applied at different time periods and sublimation time. Sucrose, Avicel RC591 and Aerosil were selected as cryoprotectants from initial screening tests. Increasing their concentration increased the particle size. 1% of Avicel RC591, 24 h of freezing at −70 • C and 48 h sublimation time showed lower growth in particle size.
Chemistry (Weinheim an der Bergstrasse, Germany), Jan 11, 2018
Adjuvant development and understanding the physicochemical properties of particles and interpreti... more Adjuvant development and understanding the physicochemical properties of particles and interpreting the subsequent immunological responses is a challenge faced by many researchers in the vaccine field. We synthesized and investigated the physicochemical properties and immunogenicity of a library of multiple epitope self-adjuvant lipopeptides in a novel asymmetric arrangement. Vaccine candidates were synthesized using a combination of solid-phase peptide synthesis and copper-mediated click chemistry. In vivo studies showed that vaccine constructs containing a single OVA CD8 T-cell epitope and two N-terminally located C16 lipid moieties were more effective at generating robust cellular immune responses compared to the same molecule containing multiple copies of the OVA CD8 T-cell epitope with or without the C16 moieties. Furthermore, attachment of the two C16 lipids to the N-terminus provoked formation of long β-sheet fibrils and was shown to induce a higher CD8 donor T-cell frequency...
Advanced drug delivery reviews, Jan 26, 2016
Self-assembled peptides have shown outstanding characteristics for vaccine delivery and drug targ... more Self-assembled peptides have shown outstanding characteristics for vaccine delivery and drug targeting. Peptide molecules can be rationally designed to self-assemble into specific nanoarchitectures in response to changes in their assembly environment including: pH, temperature, ionic strength, and interactions between host (drug) and guest molecules. The resulting supramolecular nanostructures include nanovesicles, nanofibers, nanotubes, nanoribbons, and hydrogels and have a diverse range of mechanical and physicochemical properties. These molecules can be designed for cell-specific targeting by including adhesion ligands, receptor recognition ligands, or peptide-based antigens in their design, often in a multivalent display. Depending on their design, self-assembled peptide nanostructures have advantages in biocompatibility, stability against enzymatic degradation, encapsulation of hydrophobic drugs, sustained drug release, shear-thinning viscoelastic properties, and/or adjuvanting...
Bioorganic & Medicinal Chemistry, 2016
Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of ... more Infection with Group A Streptococcus (GAS) can result in a range of different illnesses, some of which are fatal. Currently, our efforts to develop a vaccine against GAS focuses on the lipid core peptide (LCP) system, a subunit vaccine containing a lipoamino acid (LAA) moiety which allows the stimulation of systemic antibody activity. In the present study, a peptide (J14) representing the B-cell epitope from the GAS M protein was incorporated alongside a universal T-helper epitope (P25) in four LCP constructs of different spatial orientation or LAA lengths. Through structure-activity studies, it was discovered that while the alteration of the LCP orientation had a weaker effect on immunostimulation, increasing the LAA side chain length within the construct increased antibody responses in murine models. Furthermore, the mice immunised with the lead LCP construct were also able to maintain antibody activity throughout the course of five months. These findings highlight the importance of LAA moieties in the development of intranasal peptide vaccines and confirmed that its side chain length has an effect on the immunogenicity of the structure.
Bioconjugate chemistry, Jan 6, 2016
Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long bee... more Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognised as a frontline receptor in pathogen recognition. During the last decade many attempts have been made to target this receptor for applications including vaccine and drug development. In the present study, a library of vaccine constructs comprising fluorescently-labelled mannosylated lipid-dendrimers that contained the ovalbumin CD4+ epitope, OVA323-339, as the model peptide antigen were synthesised using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). The vaccine constructs were designed with an alanine spacer between the O-linked mannose moieties to investigate the impact of distance between the mannose units on receptor-mediated uptake and/or binding in APCs. Uptake studies performed on F4/80+ and CD11c+ cells showed significant uptake and/or binding for lipopeptides containing mannose, and also the lipopeptide without mannose when compared to the co...
Nanomedicine, 2015
Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features p... more Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features promoting strong CD8(+) T-cell responses. Three different self-adjuvanting lipid core peptide nanovaccines each comprising four copies of the dominant ovalbumin CD8(+) T-cell epitope and varying in the utilization of a polylysine or glucose core with 2-amino-hexadecanoic acid (C16) or 2-amino-dodecanoic acid (C12) lipids were synthesized. Vaccines were tested for ability to induce CD8(+) T-cell responses and inhibit tumor growth in vivo. The construct utilizing C12 lipids and polylysine core induced very robust effector T cells shown to have in vivo effector capability as demonstrated by in vivo cytotoxicity and ability to inhibit tumor growth as well as modulation of dendritic cell activation. The C12 polylysine platform was an effective configuration for induction of potent CD8(+) T-cell responses.
Chemistry - A European Journal, 2014
Designing a lipopeptide (LP) vaccine with a specific asymmetric arrangement of epitopes may resul... more Designing a lipopeptide (LP) vaccine with a specific asymmetric arrangement of epitopes may result in an improved display of antigens, increasing host-cell recognition and immunogenicity. This study aimed to synthesise and characterise the physicochemical properties of a library of asymmetric LP-based vaccine candidates that contained multiple CD4 + and CD8 + T-cell epitopes from the model protein antigen, ovalbumin. These fully synthetic vaccine candidates were prepared by microwave-assisted solid phase peptide synthesis. The C12 or C16 lipoamino acids were coupled to the N or C terminus of the OVA CD4 peptide epitope. The OVA CD4 LPs and OVA CD8 peptide constructs were then conjugated using azide-alkyne Huisgen cycloaddition to give multivalent synthetic vaccines. Physiochemical characterisation of these vaccines showed a tendency to self-assemble in aqueous media. Changes in lipid length and position induced self-assembly with significant changes to their morphology and secondary structure as shown by transmission electron microscopy and circular dichroism.
Aaps Pharmscitech, 2010
The aim of this study was to formulate and characterize Eudragit® L100 and Eudragit® L100-poly(la... more The aim of this study was to formulate and characterize Eudragit® L100 and Eudragit® L100-poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing diclofenac sodium. Diclofenac generates severe adverse effects with risks of toxicity. Thus, nanoparticles were prepared to reduce these drawbacks in the present study. These nanoparticles were evaluated for surface morphology, particle size and size distribution, percentage drug entrapment, and in vitro drug release in pH 6.8. The prepared nanoparticles were almost spherical in shape, as determined by atomic force microscopy. The nanoparticles with varied size (241–274 nm) and 25.8–62% of entrapment efficiency were obtained. The nanoparticles formulations produced the release profiles with an initial burst effect in which diclofenac sodium release ranged between 38% and 47% within 4 h. The extent of drug release from Eudragit® L100 nanoparticles was up to 92% at 12 h. However, Eudragit®/PLGA nanoparticles showed an initial burst release followed by a slower sustained release. The cumulative release at 72 h was 56%, 69%, and 81% for Eudragit®/PLGA (20:80), Eudragit®/PLGA (30:70) and Eudragit®/PLGA (50:50) nanoparticles, respectively. The release profiles and encapsulation efficiencies depended on the amount of Eudragit in the blend. These data demonstrated the efficacy of these nanoparticles in sustaining the diclofenac sodium release profile.
The objective of this study was to optimize a nano-lipid carrier (NLCs) of valproic acid for nasa... more The objective of this study was to optimize a nano-lipid carrier (NLCs) of valproic acid for nasal delivery using statistical methods. NLCs were prepared by solvent diffusion method followed by ultrasonication. After a preliminary screening study using Taguchi design, the Box-Behnken statistical model using desirability function was applied to evaluate variables affecting key specifications (minimum particle size, maximum drug loading and optimum release) of nano-lipid carriers of valproic acid. Each variable was assessed at three levels of surfactant concentration, acetone/ethanol volume ratio and organic/aqueous phase volume ratio. The best predicted model for particle size and drug release was quadratic model, while for drug loading, 2 factor interaction model fitted better. The measured results for the optimized formulation were a mean size of 154 nm, 47% payload and 75% of drug content released within 21 days. The optimum formulation was obtained using 1% of Poloxamer-188 as surfactant, organic/aqueous phase volume ratio of 1/5 and acetone/ethanol volume ratio of 3/1. Overall, the results show that entrapment of valproic acid in nano-lipid carriers was achieved. Such carriers might be a promising delivery system in the treatment of seizures via the nasal route of administration.
Three different formulations of a lipid-modified endomorphin-1 peptide (C 10 LAA-Endo-1) were pre... more Three different formulations of a lipid-modified endomorphin-1 peptide (C 10 LAA-Endo-1) were prepared, characterized, and evaluated for their permeability through Caco-2 cell membranes. Solid lipid nanoparticles (SLN), enteric coated (EC), and the EC-SLN of C 10 LAA-Endo-1 is a modified structure of endomorphin-1 for oral delivery. Physico-chemical characterization of the formulations showed that among all formulations, EC-[C 10 LAA-Endo-1] had the lowest particle size and the highest EE% and absolute zeta potential. Release of drug from SLN, EC-SLN and EC-[C 10 LAA-Endo-1] in acid media was 14.30 (AE2.7)%, 3.0 (AE1.0)% and 10.2 (AE3.0)%, respectively. Release data in buffer media (pH ¼ 7.4) showed that enteric coated formulations released C 10 LAA-Endo-1 more slowly than uncoated formulations. It was also demonstrated that direct coating of C 10 LAA-Endo-1 with Eudragit Õ S100 significantly enhanced the permeability of the compound through Caco-2 cell membranes with a 39-fold higher P app compared to C 10 LAA-Endo-1. These findings indicated that EC-C 10 LAA-Endo-1 is a promising candidate to promote the oral delivery of the previously modified endomorphin-1 peptide analogue and is worthy of future animal investigations.