International journal of Pharmacy and Pharmaceutical Sciences, Nov 1, 2015
This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted... more This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted microparticles using the spray drying technique. Methods: The effect of addition of different excipients namely: mannitol, leucine and ovalbumin on the physico-chemical characteristics of MTK spray dried powders were investigated. Powder flow properties, drug association efficiency as well as microparticle size and mass median aerodynamic diameter (MMAD) were determined. The prepared microparticles were characterized using FT-IR and TGA. The powder crystallographic and thermal properties were studied using DSC and X-ray powder diffraction. A twin stage impinger was used to evaluate in vitro pulmonary deposition from which the inhalation indices were derived. Results: The tested excipients showed no adverse chemical interactions with the drug based on FT-IR. The best inhalation indices were obtained with powders spray dried with leucine followed by leucine/mannitol mixtures with MMAD of 1.73±0.08 and 1.36±0.16 and fine particle fraction of 60.55±1.63 and 52.31±3.52, respectively. The dried powders showed good physico-chemical stability for up to 6 mo storage. Conclusion: The developed MTK spray dried particles may offer a good platform for the targeted pulmonary delivery of MTK overcoming the major biological barriers.
10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of n... more 10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of novel fatty acid vesicles for comparison with oleic acid (OA) ufasomes. The vesicles were loaded with magnolol (Mag), a potential natural drug for skin cancer. Different formulations were prepared using the thin film hydration method and were statistically evaluated according to a Box–Behnken design in terms of particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The ex vivo skin permeation and deposition were assessed for Mag skin delivery. In vivo, an assessment of the optimized formulae using 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer in mice was also conducted. The PS and ZP of the optimized OA vesicles were 358.9 ± 3.2 nm and −82.50 ± 7.13 mV compared to 191.9 ± 6.28 nm and −59.60 ± 3.07 mV for HDA vesicles, respectively. The EE was high (>78%) for both types of vesicles. Ex vivo permeation studies revealed enhanced Ma...
The aim of the current work was to develop a simple HPLC method for the assay of lisinopril in pl... more The aim of the current work was to develop a simple HPLC method for the assay of lisinopril in plasma. The HPLC technique was based on the use of reversed phase C8 column. The mobile phase consisted of methanol:distilled water (50:50 V/V) and pH 3.0 was adjusted using phosphoric acid. Captopril was used as an internal standard the method was validated according to ICH guidelines. The flow was adjusted to 1ml/min and the run time lasted 7 minutes. LOD and LOQ were 1.1 & 3.34 µg/ml. The intra-and inter-day precisions (relative standard deviation) were not higher than 0.5% and accuracy (relative error) did not exceed 14.3%. The linearity was observed in the range of 2.5-40 µg/mL with a coefficient of determination of 0.993. The developed method was used to calculate the pharmacokinetic parameters following oral administration of lisinopril to rabbits.
International Journal of Pharmacy and Pharmaceutical Sciences, 2015
Objective: This study focused on the preparation of montelukast sodium (MTK) fast release pulmona... more Objective: This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted microparticles using the spray drying technique. Methods: The effect of addition of different excipients namely: mannitol, leucine and ovalbumin on the physico-chemical characteristics of MTK spray dried powders were investigated. Powder flow properties, drug association efficiency as well as microparticle size and mass median aerodynamic diameter were determined. The prepared microparticles were characterized using FT-IR and TGA. The powder crystallographic and thermal properties were studied using DSC and X-ray powder diffraction. A twin stage impinger was used to evaluate in vitro pulmonary deposition from which the inhalation indices were derived. Results: The tested excipients showed no adverse chemical interactions with the drug based on FT-IR. The best inhalation indices were obtained with powders spray dried with leucine followed by leucine/mannitol mixtures with MMAD...
Objective: The objective of the present work was to optimize the formulation of chitosan/alginate... more Objective: The objective of the present work was to optimize the formulation of chitosan/alginate nanocomplexes (CS/ALG NCs) and to evaluate the effect of the amphoteric drug, repaglinide (REP), loading on NCs properties. Methods: CS/ALG NCs were prepared by ionic gelation of chitosan (CS) using sodium alginate (ALG). The effects of CS volume, and pH as well as ALG to CS mass ratio on the particle size and zeta potential of plain NCs were examined. Loading of NCs was achieved using the amphoteric drug, REP. The plain and loaded NCs were characterized using FT-IR, dynamic light scattering and transmission electron microscopy. REP dispersion and crystallographic properties in the cores of NCs were also elucidated using differential scanning calorimetry and X-ray diffraction. Results: The particle size of CS/ALG NCs and REP-loaded CS/ALG NCs was less than 400 nm with positive surface charge and spherical shape. REP loading and concentration influenced particle size (PS) as well as REP ...
Nanoliposomes (NLs) prepared by three different methods were compared in terms of their ability t... more Nanoliposomes (NLs) prepared by three different methods were compared in terms of their ability to encapsulate moxifloxacin hydrochloride (MXF). Formulation parameters namely, phospholipid to cholesterol ratio, drug to lipid ratio, and pH, were optimized. NLs with size 277.07±2.18nm and entrapment efficiency (EE) of 66.25±1.89% were obtained. The stability of MXF-NLs was enhanced by lyophilization using different ratios of trehalose. Lyophilization with lipid/trehalose ratio 1:6 was the best ratio in terms of size and EE obtained after rehydration of NLs. Amira Hamed*, Rihab Osman, Samar Mansour and Ahmed-Shawky Geneidi Faculty of Pharmacy, Ain Shams University, P.O. Box 11566, Cairo, Egypt. Submission: 2 May 2016 Accepted: 7 May 2016 Published: 25 May 2016 www.ijppr.humanjournals.com Citation: Amira Hamed et al. Ijppr.Human, 2016; Vol. 6 (2): 147-169. 148 INTRODUCTION Liposomes are well recognized controlled drug release vesicular carriers composed of one or more concentric phospho...
International Journal of Biological Macromolecules, 2020
Lipid-polysaccharide modified biohybrid nanoparticles (NPs) are eminent drug carriers for brain t... more Lipid-polysaccharide modified biohybrid nanoparticles (NPs) are eminent drug carriers for brain targeting, owing to their ability to prolong the circulation time and penetrate the blood brain barrier (BBB). Biohybrid NPs particular interest arises from their potential to mimic biological components. Herein, we prepared bioinspired lipid polymeric NPs, either naked or surface modified by a synthesized biocompatible dextran-cholic acid (DxC). The nanoprecipitation method was tailored to allow the assembly of the multicomponent NPs in a single step. Modulating the solvent/antisolvent system provided lipid polymer hybrid NPs in the size of 111.6 ± 11.4 nm size. The NPs encapsulated up to 92 ± 1.2% of a hydrophilic anti-Alzheimer drug, rivastigmine (Riv). The brain uptake, biodistribution and pharmacokinetics studies, proved the efficient fast penetration of the bioinspired surface modified NPs to the brain of healthy albino rats. The modified nanocarrier caused a 5.4 fold increase in brain targeting efficiency compared to the drug solution. Furthermore, the presence of DxC increased Riv's brain residence time up to 40 h. The achieved results suggest that the fabricated biohybrid delivery system was able to circumvent the BBB and is expected to minimize Riv systemic side effects.
International Journal of Biological Macromolecules, 2020
Improved ocular delivery of a poorly soluble anti-glaucoma drug, acetazolamide (ACZ), in a stable... more Improved ocular delivery of a poorly soluble anti-glaucoma drug, acetazolamide (ACZ), in a stable nanosuspension (NS) was the main target of the study. The anionic polypeptide, poly-γ-glutamic acid (PG) and the glycosaminoglycan, hyaluronic acid, were used to stabilize ACZ-NS prepared using the antisolvent precipitation (AS-PT) coupled with sonication technique. To endue in site biocompatibility with high tolerability, soya lecithin (SL) phospholipid has been also combined with polyvinyl alcohol (PVA). NS with uniform PS in the range 100-300 nm, high ζ > ±20 mV, and enhanced saturation solubility were produced. Targeting solvent removal with control on future particle growth, post-production processing of NS was done using spray drying. The carriers' composition and amount relative to ACZ-NS were optimized to allow for the production of a redispersible dry crystalline powder. Particles crystallinity was confirmed using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) in liquid and spray dried NS. The modified Draize test proved the safety and tolerability following application to rabbit eyes accompanying an efficient ocular hypotensive activity using a steroid glaucoma model.
Rational: Tumor immunogenic cell death (ICD), induced by certain chemotherapeutic drugs such as d... more Rational: Tumor immunogenic cell death (ICD), induced by certain chemotherapeutic drugs such as doxorubicin (Dox), is a form of apoptosis potentiating a protective immune response. One of the hallmarks of ICD is the translocation of calreticulin to the cell surface acting as an 'eat me' signal. This manuscript describes the development of a stable nucleic acid-lipid particles (SNALPs) formulation for the simultaneous delivery of ICD inducing drug (Dox) with small interfering RNA (siRNA) knocking down CD47 (siCD47), the dominant 'don't eat me' marker, for synergistic enhancement of ICD. Methods: SNALPs loaded with Dox or siCD47 either mono or combinatory platforms were prepared by ethanol injection method. The proposed systems were characterized for particle size, surface charge, entrapment efficiency and in vitro drug release. The ability of the SNALPs to preserve the siRNA integrity in presence of serum and RNAse were assessed over 48 h. The in vitro cellular uptake and gene silencing of the prepared SNALPs was assessed in CT26 cells. The immunological responses of the SNALPs were defined in vitro in terms of surface calreticulin expression and macrophage-mediated phagocytosis induction. In vivo therapeutic studies were performed in CT26 bearing mice where the therapeutic outcomes were expressed as tumor volume, expression of CD4 and CD8 as well as in vivo silencing. Results: The optimized SNALPs had a particle size 122 ±6 nm and an entrapment efficiency > 65% for both siRNA and Dox with improved serum stability. SNALPs were able to improve siRNA and Dox uptake in CT26 cells with enhanced cytotoxicity. siCD47 SNALPs were able to knockdown CD47 by approximately 70% with no interference from the presence of Dox. The siCD47 and Dox combination SNALPs were able to induce surface calreticulin expression leading to a synergistic effect on macrophage-mediated phagocytosis of treated cells. In a tumor challenge model, 50% of mice receiving siCD47 and Dox containing SNALPs were able to clear the tumor, while the remaining animals showed significantly lower tumor burden as compared to either monotreatment. Conclusion: Therefore, the combination of siCD47 and Dox in a particulate system showed potent antitumor activity which merits further investigation in future clinical studies.
Nanodiamonds (NDs) are an emerging delivery system with a massive surface area qualifying them fo... more Nanodiamonds (NDs) are an emerging delivery system with a massive surface area qualifying them for efficient loading with various drugs. However, NDs easily scavenge ions upon mixing with physiological media leading to rapid aggregation. Herein, chitosan was employed to endue steric stabilization to NDs and confer adhesiveness to the particles improving their retention in the urinary bladder. The effect of chitosan molecular weight and pH on the particle size and surface charge of chitosan-coated doxorubicin-loaded NDs (Chi-NDX) was investigated. Selected formula exhibited high drug loading efficiency (>90 %), small particle size (<150 nm), good colloidal stability, acid-favored drug release but limited stability in cell culture media. After further stabilization with TPP or dextran sulfate, selected TPP-treated formula displayed more potent cytotoxic effect compared with free doxorubicin and uncoated nanoparticles, and higher drug retention in ex vivo bovine bladder. Therefore, TPP-Chi-NDX is suggested as a promising system for mucosal anticancer delivery.
Advances in cancer nanotechnology aim at improving specificity and effectiveness for tumor treatm... more Advances in cancer nanotechnology aim at improving specificity and effectiveness for tumor treatment. Amalgamation of different treatment modalities is expected to provide better cancer combating. Herein, We developed a long circulating nanocarrier comprising trastuzumab (TZB) surface modified polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) co-encapsulating magnolol (Mag) and gold nanoparticles (GNPs). A modified single step nanoprecipitation method was adopted ensuring particle coating with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) while co-encapsulating GNPs. TZB was then anchored on NPs surface using a carbodiimide chemistry. The cytotoxicity of the developed system was evaluated with and without photothermal irradiation. NPs cellular uptake was then followed using confocal microscopical imaging. A hybrid matrix composed of PLGA/TPGS and surface decorated with TZB with a conjugation efficiency of ˃65%, was confirmed via FTIR, 1HNMR. GNPs could only be includ...
Journal of Drug Delivery Science and Technology, 2019
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Remarkable efforts are currently devoted to the area of nanodiamonds (NDs) research due to their ... more Remarkable efforts are currently devoted to the area of nanodiamonds (NDs) research due to their superior properties viz: biocompatibility, minute size, inert core, and tunable surface chemistry. The use of NDs for the delivery of anticancer drugs has been at the forefront of NDs applications owing to their ability to increase chemosensitivity, sustain drug release, and minimize drug side effects. Accelerated steps towards the move of NDs from bench side to bedside have been recently witnessed. In this review, the effects of NDs production and purification techniques on NDs' final properties are discussed. Special concern is given to studies focusing on NDs use for anticancer drug delivery, stability enhancement and mediated targeted delivery. The aim of this review is to put the results of studies oriented towards NDsmediated anticancer drug delivery side by side such that the reader can assess the potential use of NDs in clinics and follow up the upcoming results of clinical testing of NDs on animals and humans.
Materials and Methods Chemicals, reagents and kits 1,2-dioleoyl-3-trimethylammonium-propane chlor... more Materials and Methods Chemicals, reagents and kits 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP), Bradford reagent, Freund's adjuvant, Amberlite XAD-2, carbonate buffer, ethidium bromide, methylene blue, trifluoroacetic acid, HPLC grade methanol, chloroform, Dulbecco's modified Eagle's medium (DMEM), [3-(4,5-dimethylthiazol)-2-yl]-2,5diphenyltetrazolium bromide (MTT), Fetal bovine serum (FBS), Trypsin/ EDTA solution were purchased from Sigma Aldrich, Germany. Uranyl acetate-2-hydrate was purchased from Allied Signal, Germany. ELISA washing, blocking and stopping buffers were purchased from Serva Electrophoresis GmbH, Germany. Alkaline phosphatase-conjugated goat anti-mouse IgG antibodies and p-nitrophenyl phosphate (pNPP) Microwell Substrate System were purchased from KPL Company, USA. 244-bp STa and 450-bp K99 primers were purchased from Alpha DNA, Canada. EmeraldAmp GT PCR Master Mix was purchased from Takara Bio Europe, France. Molecular biology grade water and agarose gel were purchased from Lonza, Belgium. Standard synthetic STa peptide was purchased from Pipmec Company, China. Soyabean lecithin (Epikuron 200) was kindly provided by Cargill Company, Germany. A549 cell line was purchased from ATCC (Rockville, USA). Other chemicals and reagents were purchased from local commercial source.
International journal of Pharmacy and Pharmaceutical Sciences, Nov 1, 2015
This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted... more This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted microparticles using the spray drying technique. Methods: The effect of addition of different excipients namely: mannitol, leucine and ovalbumin on the physico-chemical characteristics of MTK spray dried powders were investigated. Powder flow properties, drug association efficiency as well as microparticle size and mass median aerodynamic diameter (MMAD) were determined. The prepared microparticles were characterized using FT-IR and TGA. The powder crystallographic and thermal properties were studied using DSC and X-ray powder diffraction. A twin stage impinger was used to evaluate in vitro pulmonary deposition from which the inhalation indices were derived. Results: The tested excipients showed no adverse chemical interactions with the drug based on FT-IR. The best inhalation indices were obtained with powders spray dried with leucine followed by leucine/mannitol mixtures with MMAD of 1.73±0.08 and 1.36±0.16 and fine particle fraction of 60.55±1.63 and 52.31±3.52, respectively. The dried powders showed good physico-chemical stability for up to 6 mo storage. Conclusion: The developed MTK spray dried particles may offer a good platform for the targeted pulmonary delivery of MTK overcoming the major biological barriers.
10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of n... more 10-hydroxy decanoic acid (HDA), a naturally derived fatty acid, was used for the preparation of novel fatty acid vesicles for comparison with oleic acid (OA) ufasomes. The vesicles were loaded with magnolol (Mag), a potential natural drug for skin cancer. Different formulations were prepared using the thin film hydration method and were statistically evaluated according to a Box–Behnken design in terms of particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). The ex vivo skin permeation and deposition were assessed for Mag skin delivery. In vivo, an assessment of the optimized formulae using 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer in mice was also conducted. The PS and ZP of the optimized OA vesicles were 358.9 ± 3.2 nm and −82.50 ± 7.13 mV compared to 191.9 ± 6.28 nm and −59.60 ± 3.07 mV for HDA vesicles, respectively. The EE was high (>78%) for both types of vesicles. Ex vivo permeation studies revealed enhanced Ma...
The aim of the current work was to develop a simple HPLC method for the assay of lisinopril in pl... more The aim of the current work was to develop a simple HPLC method for the assay of lisinopril in plasma. The HPLC technique was based on the use of reversed phase C8 column. The mobile phase consisted of methanol:distilled water (50:50 V/V) and pH 3.0 was adjusted using phosphoric acid. Captopril was used as an internal standard the method was validated according to ICH guidelines. The flow was adjusted to 1ml/min and the run time lasted 7 minutes. LOD and LOQ were 1.1 & 3.34 µg/ml. The intra-and inter-day precisions (relative standard deviation) were not higher than 0.5% and accuracy (relative error) did not exceed 14.3%. The linearity was observed in the range of 2.5-40 µg/mL with a coefficient of determination of 0.993. The developed method was used to calculate the pharmacokinetic parameters following oral administration of lisinopril to rabbits.
International Journal of Pharmacy and Pharmaceutical Sciences, 2015
Objective: This study focused on the preparation of montelukast sodium (MTK) fast release pulmona... more Objective: This study focused on the preparation of montelukast sodium (MTK) fast release pulmonary targeted microparticles using the spray drying technique. Methods: The effect of addition of different excipients namely: mannitol, leucine and ovalbumin on the physico-chemical characteristics of MTK spray dried powders were investigated. Powder flow properties, drug association efficiency as well as microparticle size and mass median aerodynamic diameter were determined. The prepared microparticles were characterized using FT-IR and TGA. The powder crystallographic and thermal properties were studied using DSC and X-ray powder diffraction. A twin stage impinger was used to evaluate in vitro pulmonary deposition from which the inhalation indices were derived. Results: The tested excipients showed no adverse chemical interactions with the drug based on FT-IR. The best inhalation indices were obtained with powders spray dried with leucine followed by leucine/mannitol mixtures with MMAD...
Objective: The objective of the present work was to optimize the formulation of chitosan/alginate... more Objective: The objective of the present work was to optimize the formulation of chitosan/alginate nanocomplexes (CS/ALG NCs) and to evaluate the effect of the amphoteric drug, repaglinide (REP), loading on NCs properties. Methods: CS/ALG NCs were prepared by ionic gelation of chitosan (CS) using sodium alginate (ALG). The effects of CS volume, and pH as well as ALG to CS mass ratio on the particle size and zeta potential of plain NCs were examined. Loading of NCs was achieved using the amphoteric drug, REP. The plain and loaded NCs were characterized using FT-IR, dynamic light scattering and transmission electron microscopy. REP dispersion and crystallographic properties in the cores of NCs were also elucidated using differential scanning calorimetry and X-ray diffraction. Results: The particle size of CS/ALG NCs and REP-loaded CS/ALG NCs was less than 400 nm with positive surface charge and spherical shape. REP loading and concentration influenced particle size (PS) as well as REP ...
Nanoliposomes (NLs) prepared by three different methods were compared in terms of their ability t... more Nanoliposomes (NLs) prepared by three different methods were compared in terms of their ability to encapsulate moxifloxacin hydrochloride (MXF). Formulation parameters namely, phospholipid to cholesterol ratio, drug to lipid ratio, and pH, were optimized. NLs with size 277.07±2.18nm and entrapment efficiency (EE) of 66.25±1.89% were obtained. The stability of MXF-NLs was enhanced by lyophilization using different ratios of trehalose. Lyophilization with lipid/trehalose ratio 1:6 was the best ratio in terms of size and EE obtained after rehydration of NLs. Amira Hamed*, Rihab Osman, Samar Mansour and Ahmed-Shawky Geneidi Faculty of Pharmacy, Ain Shams University, P.O. Box 11566, Cairo, Egypt. Submission: 2 May 2016 Accepted: 7 May 2016 Published: 25 May 2016 www.ijppr.humanjournals.com Citation: Amira Hamed et al. Ijppr.Human, 2016; Vol. 6 (2): 147-169. 148 INTRODUCTION Liposomes are well recognized controlled drug release vesicular carriers composed of one or more concentric phospho...
International Journal of Biological Macromolecules, 2020
Lipid-polysaccharide modified biohybrid nanoparticles (NPs) are eminent drug carriers for brain t... more Lipid-polysaccharide modified biohybrid nanoparticles (NPs) are eminent drug carriers for brain targeting, owing to their ability to prolong the circulation time and penetrate the blood brain barrier (BBB). Biohybrid NPs particular interest arises from their potential to mimic biological components. Herein, we prepared bioinspired lipid polymeric NPs, either naked or surface modified by a synthesized biocompatible dextran-cholic acid (DxC). The nanoprecipitation method was tailored to allow the assembly of the multicomponent NPs in a single step. Modulating the solvent/antisolvent system provided lipid polymer hybrid NPs in the size of 111.6 ± 11.4 nm size. The NPs encapsulated up to 92 ± 1.2% of a hydrophilic anti-Alzheimer drug, rivastigmine (Riv). The brain uptake, biodistribution and pharmacokinetics studies, proved the efficient fast penetration of the bioinspired surface modified NPs to the brain of healthy albino rats. The modified nanocarrier caused a 5.4 fold increase in brain targeting efficiency compared to the drug solution. Furthermore, the presence of DxC increased Riv's brain residence time up to 40 h. The achieved results suggest that the fabricated biohybrid delivery system was able to circumvent the BBB and is expected to minimize Riv systemic side effects.
International Journal of Biological Macromolecules, 2020
Improved ocular delivery of a poorly soluble anti-glaucoma drug, acetazolamide (ACZ), in a stable... more Improved ocular delivery of a poorly soluble anti-glaucoma drug, acetazolamide (ACZ), in a stable nanosuspension (NS) was the main target of the study. The anionic polypeptide, poly-γ-glutamic acid (PG) and the glycosaminoglycan, hyaluronic acid, were used to stabilize ACZ-NS prepared using the antisolvent precipitation (AS-PT) coupled with sonication technique. To endue in site biocompatibility with high tolerability, soya lecithin (SL) phospholipid has been also combined with polyvinyl alcohol (PVA). NS with uniform PS in the range 100-300 nm, high ζ > ±20 mV, and enhanced saturation solubility were produced. Targeting solvent removal with control on future particle growth, post-production processing of NS was done using spray drying. The carriers' composition and amount relative to ACZ-NS were optimized to allow for the production of a redispersible dry crystalline powder. Particles crystallinity was confirmed using X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) in liquid and spray dried NS. The modified Draize test proved the safety and tolerability following application to rabbit eyes accompanying an efficient ocular hypotensive activity using a steroid glaucoma model.
Rational: Tumor immunogenic cell death (ICD), induced by certain chemotherapeutic drugs such as d... more Rational: Tumor immunogenic cell death (ICD), induced by certain chemotherapeutic drugs such as doxorubicin (Dox), is a form of apoptosis potentiating a protective immune response. One of the hallmarks of ICD is the translocation of calreticulin to the cell surface acting as an 'eat me' signal. This manuscript describes the development of a stable nucleic acid-lipid particles (SNALPs) formulation for the simultaneous delivery of ICD inducing drug (Dox) with small interfering RNA (siRNA) knocking down CD47 (siCD47), the dominant 'don't eat me' marker, for synergistic enhancement of ICD. Methods: SNALPs loaded with Dox or siCD47 either mono or combinatory platforms were prepared by ethanol injection method. The proposed systems were characterized for particle size, surface charge, entrapment efficiency and in vitro drug release. The ability of the SNALPs to preserve the siRNA integrity in presence of serum and RNAse were assessed over 48 h. The in vitro cellular uptake and gene silencing of the prepared SNALPs was assessed in CT26 cells. The immunological responses of the SNALPs were defined in vitro in terms of surface calreticulin expression and macrophage-mediated phagocytosis induction. In vivo therapeutic studies were performed in CT26 bearing mice where the therapeutic outcomes were expressed as tumor volume, expression of CD4 and CD8 as well as in vivo silencing. Results: The optimized SNALPs had a particle size 122 ±6 nm and an entrapment efficiency > 65% for both siRNA and Dox with improved serum stability. SNALPs were able to improve siRNA and Dox uptake in CT26 cells with enhanced cytotoxicity. siCD47 SNALPs were able to knockdown CD47 by approximately 70% with no interference from the presence of Dox. The siCD47 and Dox combination SNALPs were able to induce surface calreticulin expression leading to a synergistic effect on macrophage-mediated phagocytosis of treated cells. In a tumor challenge model, 50% of mice receiving siCD47 and Dox containing SNALPs were able to clear the tumor, while the remaining animals showed significantly lower tumor burden as compared to either monotreatment. Conclusion: Therefore, the combination of siCD47 and Dox in a particulate system showed potent antitumor activity which merits further investigation in future clinical studies.
Nanodiamonds (NDs) are an emerging delivery system with a massive surface area qualifying them fo... more Nanodiamonds (NDs) are an emerging delivery system with a massive surface area qualifying them for efficient loading with various drugs. However, NDs easily scavenge ions upon mixing with physiological media leading to rapid aggregation. Herein, chitosan was employed to endue steric stabilization to NDs and confer adhesiveness to the particles improving their retention in the urinary bladder. The effect of chitosan molecular weight and pH on the particle size and surface charge of chitosan-coated doxorubicin-loaded NDs (Chi-NDX) was investigated. Selected formula exhibited high drug loading efficiency (>90 %), small particle size (<150 nm), good colloidal stability, acid-favored drug release but limited stability in cell culture media. After further stabilization with TPP or dextran sulfate, selected TPP-treated formula displayed more potent cytotoxic effect compared with free doxorubicin and uncoated nanoparticles, and higher drug retention in ex vivo bovine bladder. Therefore, TPP-Chi-NDX is suggested as a promising system for mucosal anticancer delivery.
Advances in cancer nanotechnology aim at improving specificity and effectiveness for tumor treatm... more Advances in cancer nanotechnology aim at improving specificity and effectiveness for tumor treatment. Amalgamation of different treatment modalities is expected to provide better cancer combating. Herein, We developed a long circulating nanocarrier comprising trastuzumab (TZB) surface modified polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) co-encapsulating magnolol (Mag) and gold nanoparticles (GNPs). A modified single step nanoprecipitation method was adopted ensuring particle coating with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) while co-encapsulating GNPs. TZB was then anchored on NPs surface using a carbodiimide chemistry. The cytotoxicity of the developed system was evaluated with and without photothermal irradiation. NPs cellular uptake was then followed using confocal microscopical imaging. A hybrid matrix composed of PLGA/TPGS and surface decorated with TZB with a conjugation efficiency of ˃65%, was confirmed via FTIR, 1HNMR. GNPs could only be includ...
Journal of Drug Delivery Science and Technology, 2019
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Remarkable efforts are currently devoted to the area of nanodiamonds (NDs) research due to their ... more Remarkable efforts are currently devoted to the area of nanodiamonds (NDs) research due to their superior properties viz: biocompatibility, minute size, inert core, and tunable surface chemistry. The use of NDs for the delivery of anticancer drugs has been at the forefront of NDs applications owing to their ability to increase chemosensitivity, sustain drug release, and minimize drug side effects. Accelerated steps towards the move of NDs from bench side to bedside have been recently witnessed. In this review, the effects of NDs production and purification techniques on NDs' final properties are discussed. Special concern is given to studies focusing on NDs use for anticancer drug delivery, stability enhancement and mediated targeted delivery. The aim of this review is to put the results of studies oriented towards NDsmediated anticancer drug delivery side by side such that the reader can assess the potential use of NDs in clinics and follow up the upcoming results of clinical testing of NDs on animals and humans.
Materials and Methods Chemicals, reagents and kits 1,2-dioleoyl-3-trimethylammonium-propane chlor... more Materials and Methods Chemicals, reagents and kits 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP), Bradford reagent, Freund's adjuvant, Amberlite XAD-2, carbonate buffer, ethidium bromide, methylene blue, trifluoroacetic acid, HPLC grade methanol, chloroform, Dulbecco's modified Eagle's medium (DMEM), [3-(4,5-dimethylthiazol)-2-yl]-2,5diphenyltetrazolium bromide (MTT), Fetal bovine serum (FBS), Trypsin/ EDTA solution were purchased from Sigma Aldrich, Germany. Uranyl acetate-2-hydrate was purchased from Allied Signal, Germany. ELISA washing, blocking and stopping buffers were purchased from Serva Electrophoresis GmbH, Germany. Alkaline phosphatase-conjugated goat anti-mouse IgG antibodies and p-nitrophenyl phosphate (pNPP) Microwell Substrate System were purchased from KPL Company, USA. 244-bp STa and 450-bp K99 primers were purchased from Alpha DNA, Canada. EmeraldAmp GT PCR Master Mix was purchased from Takara Bio Europe, France. Molecular biology grade water and agarose gel were purchased from Lonza, Belgium. Standard synthetic STa peptide was purchased from Pipmec Company, China. Soyabean lecithin (Epikuron 200) was kindly provided by Cargill Company, Germany. A549 cell line was purchased from ATCC (Rockville, USA). Other chemicals and reagents were purchased from local commercial source.
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