Nasir Hussain - Academia.edu (original) (raw)
Papers by Nasir Hussain
Journal of Drug Targeting, 1995
Quantitative and qualitative evidence from our laboratories on the absorption and translocation o... more Quantitative and qualitative evidence from our laboratories on the absorption and translocation of polystyrene latex nanoparticles both by histological (qualitative) and analytical measurement of levels of polystyrene (quantitative) is briefly reviewed in this paper. We have previously compared the uptake of nonionized polystyrene latex ranging in size from 50nm to 3 microns, and made some comparisons of uptake between carboxylated microspheres and nonionic systems, showing the lower uptake of the former through the lymphoid tissue of the gastrointestinal tract. Size is a key parameter, uptake increasing with decreasing particle diameter. Early evidence suggested that uptake is by way of the Peyer's patches and other elements of the gut associated lymphoid tissue (GALT). Adsorption of hydrophilic block-copolymers onto polystyrene markedly reduces the uptake by intestinal GALT. Modification of the surface with specific ligands such as by covalent attachment of tomato lectin molecules has indicated widespread uptake by non-GALT tissues, following their binding to and internalisation by enterocytes. The ability to decrease and increase uptake is clear evidence of a phenomenon which has the potential for further control to allow it to be exploited fully for drug or vaccine delivery. The evidence to date with nanoparticles as carriers systems for labile drugs such as proteins by the oral route remains to be substantiated.
Advanced Drug Delivery Reviews, 2001
Journal of Controlled Release, 1996
Poly(&xyUc acid) derivatives UC commonly used as phartnaceutical excipiem. Tlxtr pmpenics am inte... more Poly(&xyUc acid) derivatives UC commonly used as phartnaceutical excipiem. Tlxtr pmpenics am inteosivdy investigated. They are also appmved by the FDA as generally recognized a safe. 'Gte sin of the study wy1s to investigate whether the two biodherive poly(scry,ates) polycarbo#til (PCP. Nowoo* AAI) and carbooter (C934P. Carbopol* 934 P. both obabted from BF Goodrich. Ckvelmd. Ohio. USA) are able to reduce two intesdnll physiological barrier pmpenies against peptide drug absorpio& namely a) Be pmteolyticll activity sod b) the paraceUulv integrity of the intestinal epitbeliurr.
Journal of Controlled Release, 1995
Previous work from our laboratories has provided quantitative proof of the importance of the gut ... more Previous work from our laboratories has provided quantitative proof of the importance of the gut associated lymphoid tissue (GALT) in the processes involved in the uptake of polystyrene nanoparticles delivered orally, and has confirmed the role of the Peyer's patches in the uptake of particles through the small intestine. In more recent work discussed here the role of lymphoid tissue in the large intestine has been demonstrated, a significant amount of the total uptake occurring in this region of the gut. Adsorption of poloxamers 188 and 407 onto 50 nm polystyrene nanopartictes inhibited uptake in the small intestine and reduced uptake from the large intestine, suggesting reduction in adhesion to GALT and other epithelial tissues in the presence of the poloxamer coating but also indirectly suggesting differences in the surface characteristics of lymphoid tissue at different sites in the gut. The covalent attachment of tomato (Lycopersicon esculentum) lectin molecules to the surface of 500 nm polystyrene particles had a significant effect not only on total uptake (well over a 10-fold increase in absorption over 'plain' particles after 5 days daily dosing) but on the locus of uptake, which is shifted from lymphoid to normal non-lymphoid intestinal tissue. We have demonstrated, therefore, both an increase and a decrease in absorption of nanoparticles from the gastro-intestinal tract and some, albeit serendipitous, control of the site of uptake and absorption, which should provide pointers for the future development of systems with optimal uptake characteristics.
Pharmaceutical Research, 1998
Pharmaceutical Research, 1997
Purpose. To investigate the usefulness of a surface-conjugated, bioadhesive molecule, tomato lect... more Purpose. To investigate the usefulness of a surface-conjugated, bioadhesive molecule, tomato lectin, to augment intestinal uptake of orally administered inert nanoparticles. Methods. Fluorescent 500 nm polystyrene nanoparticles with tomato lectin covalently surface coupled using a carbodiimide reaction were administered to female Wistar rats by oral gavage daily for 5 days. Results. Analysis of tissue extracted polymer by gel permeation chromatography revealed a 23% systemic uptake of tomato lectin conjugated nanoparticles compared to < 0.5% of TL nanoparticles blocked with N-acetylchitotetraose thus representing an increase of almost 50 fold across the intestine. Intestinal uptake of tomato lectin-conjugated nanoparticles via the villous tissue was 15 times higher than uptake by the gut-associated lymphoid tissue. Conclusions. The application of tomato lectin as a bioadhesive agent in vivo has been demonstrated to enhance subsequent intestinal transcytosis of colloidal particulates to which it is bound.
Journal of Pharmacy and Pharmacology, 2003
Plasmid DNA was adsorbed onto 87-nm gold nanoparticles to which were adsorbed a layer of novel ca... more Plasmid DNA was adsorbed onto 87-nm gold nanoparticles to which were adsorbed a layer of novel cationic dendrons. The behaviour of this DNA-dendron-gold system in cell culture media has been described. Adsorption onto the gold nanoparticles of lipophilic cationic dendrons, with either 8 [(C 12 ) 3 Lys 7 (NH 2 ) 8 ] or 16 [(C 12 ) 3 Lys 15 (NH 2 ) 1 6 ] free amino groups on their outer surfaces and incorporating a nuclear localization signal peptide (NLS), resulted in positively charged nanoparticles with a corresponding small increase in particle size. Evidence suggested that the interaction between the gold nanoparticles and the dendron was mediated by hydrophobic forces. With an increase in ionic strength, the apparent particle size of the dendron-stabilized-gold particles increased, but at higher salt concentrations than plain gold sols. Addition of plasmid DNA did not markedly reduce the surface potential of the dendron-gold complex but resulted in an approximately 10-20% increase in hydro-dynamic diameter. Increasing ionic strength increased the apparent size of the DNA-dendrongold particles, up to a maximum diameter of approximately 900 nm. Importantly, in cell culture media the size of the DNA-dendron-gold nanoparticles increased markedly, as surface potential was reduced. The presence of serum components partially ameliorated these effects, possibly due to steric stabilization of the particles. Release of the DNA from the complex was compromised in cell culture media (compared with water). This, coupled with the flocculation of the carrier, demonstrated the importance of testing delivery systems in the presence of relevant physiologically based fluids before cell culture or in-vivo studies.
Advanced Drug Delivery Reviews, 2001
The translocation of particulate matter across the gastrointestinal tract is now a well documente... more The translocation of particulate matter across the gastrointestinal tract is now a well documented phenomenon offering new potential for the delivery of drugs with poor dissolution profiles and labile chemistries via encapsulation in biodegradable nanoparticles. The last few years have seen an acceleration in the number of publications describing the varying facets of this approach and the multidisciplinary nature of this field. This review delineates data from this rather fragmented area and from cognate fields to provide a physicochemical viewpoint of the importance of surface chemistries of oral drug delivery vehicles and their interactions in and with gut contents prior to uptake. The role of lymphoid and non-lymphoid tissues is examined, and the role of bioadhesion is discussed. The exciting potential of molecular encapsulation of drugs via dendrimers and star branched molecules is discussed in the context of nanotechnological applications for the oral route. Evolving vistas include a better understanding of the plasticity of the intestinal epithelium and M-cell induction as well as the influence of disease states on particulate uptake. In this review we address a number of issues deemed vital to an understanding of the subject including (i) some background knowledge on particulate uptake (the subject of several reviews), (ii) factors affecting uptake such as diameter and surface charge and character, (iii) the dynamic nature of particle interactions in the gut, (iv) the dynamic nature of the processes of capture, adhesion, uptake, transcytosis and translocation, and (v) the influence of surface ligands.
Companies have already begun to realize the importance of internal operations and the knowledge d... more Companies have already begun to realize the importance of internal operations and the knowledge driven environment within a company. The effectiveness to contribute towards new knowledge useful for the company, that is, innovation by an employee is dependent on his/her perception of the organization. Using data obtained from an Indian software company, this study examines the effect of some important organizational factors on the "innovation" dimension of its employees, that is, the ability to generate and stimulate creativity and innovation. The study supports the fact that the employee's perception of organizational culture has an impact on the employee's performance on the innovation dimension of performance. Therefore, it is the 'feeling' that guides the individual's behaviour. Thus, the perceived congeniality in the working culture duly supported by the supervisor's encouragement and acceptance of an idea and its reinforcement by appropriate recognition and rewards fosters innovation in the organization. The study also discusses its implications for the industry.
Journal of Drug Targeting, 1995
Quantitative and qualitative evidence from our laboratories on the absorption and translocation o... more Quantitative and qualitative evidence from our laboratories on the absorption and translocation of polystyrene latex nanoparticles both by histological (qualitative) and analytical measurement of levels of polystyrene (quantitative) is briefly reviewed in this paper. We have previously compared the uptake of nonionized polystyrene latex ranging in size from 50nm to 3 microns, and made some comparisons of uptake between carboxylated microspheres and nonionic systems, showing the lower uptake of the former through the lymphoid tissue of the gastrointestinal tract. Size is a key parameter, uptake increasing with decreasing particle diameter. Early evidence suggested that uptake is by way of the Peyer's patches and other elements of the gut associated lymphoid tissue (GALT). Adsorption of hydrophilic block-copolymers onto polystyrene markedly reduces the uptake by intestinal GALT. Modification of the surface with specific ligands such as by covalent attachment of tomato lectin molecules has indicated widespread uptake by non-GALT tissues, following their binding to and internalisation by enterocytes. The ability to decrease and increase uptake is clear evidence of a phenomenon which has the potential for further control to allow it to be exploited fully for drug or vaccine delivery. The evidence to date with nanoparticles as carriers systems for labile drugs such as proteins by the oral route remains to be substantiated.
Advanced Drug Delivery Reviews, 2001
Journal of Controlled Release, 1996
Poly(&xyUc acid) derivatives UC commonly used as phartnaceutical excipiem. Tlxtr pmpenics am inte... more Poly(&xyUc acid) derivatives UC commonly used as phartnaceutical excipiem. Tlxtr pmpenics am inteosivdy investigated. They are also appmved by the FDA as generally recognized a safe. 'Gte sin of the study wy1s to investigate whether the two biodherive poly(scry,ates) polycarbo#til (PCP. Nowoo* AAI) and carbooter (C934P. Carbopol* 934 P. both obabted from BF Goodrich. Ckvelmd. Ohio. USA) are able to reduce two intesdnll physiological barrier pmpenies against peptide drug absorpio& namely a) Be pmteolyticll activity sod b) the paraceUulv integrity of the intestinal epitbeliurr.
Journal of Controlled Release, 1995
Previous work from our laboratories has provided quantitative proof of the importance of the gut ... more Previous work from our laboratories has provided quantitative proof of the importance of the gut associated lymphoid tissue (GALT) in the processes involved in the uptake of polystyrene nanoparticles delivered orally, and has confirmed the role of the Peyer's patches in the uptake of particles through the small intestine. In more recent work discussed here the role of lymphoid tissue in the large intestine has been demonstrated, a significant amount of the total uptake occurring in this region of the gut. Adsorption of poloxamers 188 and 407 onto 50 nm polystyrene nanopartictes inhibited uptake in the small intestine and reduced uptake from the large intestine, suggesting reduction in adhesion to GALT and other epithelial tissues in the presence of the poloxamer coating but also indirectly suggesting differences in the surface characteristics of lymphoid tissue at different sites in the gut. The covalent attachment of tomato (Lycopersicon esculentum) lectin molecules to the surface of 500 nm polystyrene particles had a significant effect not only on total uptake (well over a 10-fold increase in absorption over 'plain' particles after 5 days daily dosing) but on the locus of uptake, which is shifted from lymphoid to normal non-lymphoid intestinal tissue. We have demonstrated, therefore, both an increase and a decrease in absorption of nanoparticles from the gastro-intestinal tract and some, albeit serendipitous, control of the site of uptake and absorption, which should provide pointers for the future development of systems with optimal uptake characteristics.
Pharmaceutical Research, 1998
Pharmaceutical Research, 1997
Purpose. To investigate the usefulness of a surface-conjugated, bioadhesive molecule, tomato lect... more Purpose. To investigate the usefulness of a surface-conjugated, bioadhesive molecule, tomato lectin, to augment intestinal uptake of orally administered inert nanoparticles. Methods. Fluorescent 500 nm polystyrene nanoparticles with tomato lectin covalently surface coupled using a carbodiimide reaction were administered to female Wistar rats by oral gavage daily for 5 days. Results. Analysis of tissue extracted polymer by gel permeation chromatography revealed a 23% systemic uptake of tomato lectin conjugated nanoparticles compared to < 0.5% of TL nanoparticles blocked with N-acetylchitotetraose thus representing an increase of almost 50 fold across the intestine. Intestinal uptake of tomato lectin-conjugated nanoparticles via the villous tissue was 15 times higher than uptake by the gut-associated lymphoid tissue. Conclusions. The application of tomato lectin as a bioadhesive agent in vivo has been demonstrated to enhance subsequent intestinal transcytosis of colloidal particulates to which it is bound.
Journal of Pharmacy and Pharmacology, 2003
Plasmid DNA was adsorbed onto 87-nm gold nanoparticles to which were adsorbed a layer of novel ca... more Plasmid DNA was adsorbed onto 87-nm gold nanoparticles to which were adsorbed a layer of novel cationic dendrons. The behaviour of this DNA-dendron-gold system in cell culture media has been described. Adsorption onto the gold nanoparticles of lipophilic cationic dendrons, with either 8 [(C 12 ) 3 Lys 7 (NH 2 ) 8 ] or 16 [(C 12 ) 3 Lys 15 (NH 2 ) 1 6 ] free amino groups on their outer surfaces and incorporating a nuclear localization signal peptide (NLS), resulted in positively charged nanoparticles with a corresponding small increase in particle size. Evidence suggested that the interaction between the gold nanoparticles and the dendron was mediated by hydrophobic forces. With an increase in ionic strength, the apparent particle size of the dendron-stabilized-gold particles increased, but at higher salt concentrations than plain gold sols. Addition of plasmid DNA did not markedly reduce the surface potential of the dendron-gold complex but resulted in an approximately 10-20% increase in hydro-dynamic diameter. Increasing ionic strength increased the apparent size of the DNA-dendrongold particles, up to a maximum diameter of approximately 900 nm. Importantly, in cell culture media the size of the DNA-dendron-gold nanoparticles increased markedly, as surface potential was reduced. The presence of serum components partially ameliorated these effects, possibly due to steric stabilization of the particles. Release of the DNA from the complex was compromised in cell culture media (compared with water). This, coupled with the flocculation of the carrier, demonstrated the importance of testing delivery systems in the presence of relevant physiologically based fluids before cell culture or in-vivo studies.
Advanced Drug Delivery Reviews, 2001
The translocation of particulate matter across the gastrointestinal tract is now a well documente... more The translocation of particulate matter across the gastrointestinal tract is now a well documented phenomenon offering new potential for the delivery of drugs with poor dissolution profiles and labile chemistries via encapsulation in biodegradable nanoparticles. The last few years have seen an acceleration in the number of publications describing the varying facets of this approach and the multidisciplinary nature of this field. This review delineates data from this rather fragmented area and from cognate fields to provide a physicochemical viewpoint of the importance of surface chemistries of oral drug delivery vehicles and their interactions in and with gut contents prior to uptake. The role of lymphoid and non-lymphoid tissues is examined, and the role of bioadhesion is discussed. The exciting potential of molecular encapsulation of drugs via dendrimers and star branched molecules is discussed in the context of nanotechnological applications for the oral route. Evolving vistas include a better understanding of the plasticity of the intestinal epithelium and M-cell induction as well as the influence of disease states on particulate uptake. In this review we address a number of issues deemed vital to an understanding of the subject including (i) some background knowledge on particulate uptake (the subject of several reviews), (ii) factors affecting uptake such as diameter and surface charge and character, (iii) the dynamic nature of particle interactions in the gut, (iv) the dynamic nature of the processes of capture, adhesion, uptake, transcytosis and translocation, and (v) the influence of surface ligands.
Companies have already begun to realize the importance of internal operations and the knowledge d... more Companies have already begun to realize the importance of internal operations and the knowledge driven environment within a company. The effectiveness to contribute towards new knowledge useful for the company, that is, innovation by an employee is dependent on his/her perception of the organization. Using data obtained from an Indian software company, this study examines the effect of some important organizational factors on the "innovation" dimension of its employees, that is, the ability to generate and stimulate creativity and innovation. The study supports the fact that the employee's perception of organizational culture has an impact on the employee's performance on the innovation dimension of performance. Therefore, it is the 'feeling' that guides the individual's behaviour. Thus, the perceived congeniality in the working culture duly supported by the supervisor's encouragement and acceptance of an idea and its reinforcement by appropriate recognition and rewards fosters innovation in the organization. The study also discusses its implications for the industry.