Biomedical subjects

S M Moghimi

Publications and source records attributed to S M Moghimi.

44 records · Page 3Linked to original sources

PubMed1990

Calcium as a possible modulator of Kupffer cell phagocytic function by regulating liver-specific opsonic activity.

Recently we described some properties of organ-specific serum opsonins which differentiate between liver- and spleen-specific opsonic activities, and reported that, on dialysis of serum, its liver opsonic activity is enhanced by 2- to 3-fold, whereas spleen-specific activity is reduced by 20-30% of that of control serum (Moghimi, S.M. and Patel, H.M. (1989) Biochim. Biophys. Acta 984, 379-383). This observation suggests that serum contains dialysable factors which regulate liver- as well as spleen-specific opsonic activities. Our results from EGTA-treated serum suggest that dialysable factor(s) could be divalent cations such as Ca2+, Mn2+, Mg2+ or Co2+, and among them, calcium may be the key regulatory factor for liver-specific opsonic activity. The regulatory mechanism of spleen-specific opsonic activity seems to be complex, since addition of dialysate or calcium or magnesium to the dialysed serum does not restore its activity; probably the removal of divalent cations has induced an irreversible conformational change in spleen-specific opsonin. In conclusion, we propose that the blood calcium concentration may play an important role in modulating hepatic phagocytic function by modifying liver-specific opsonic activity in serum. An increase in the physiological concentration of calcium will suppress and a decrease will enhance this opsonic activity.

Animals↗

PubMed1990

Physiopathological and physicochemical considerations in targeting of colloids and drug carriers to the bone marrow.

The ability of the bone marrow to remove particulate matters from the circulation, opens up perhaps an opportunity for the delivery of therapeutic agents by means of colloidal drug carrier systems such as liposomes, emulsions, nanoparticles, etc. for the treatment of diseases and disorders of this multifunctional organ of the body. This article is designed to provide a critical review on fundamentals, problems, current progress, and future prospects of site-specific delivery of intravenously injected colloidal drug carriers to the bone marrow.

Animals↗

PubMed1989

Differential properties of organ-specific serum opsonins for liver and spleen macrophages.

Earlier we reported that serum contains organ-specific opsonins which selectively enhance recognition of liposomes by macrophages in the specific organs of the reticuloendothelial system (Moghimi, S.M. and Patel, H.M. (1988) FEBS Lett. 233, 143-147). The results presented here describe the properties of these organ-specific opsonins which differentiate between liver-specific and spleen-specific opsonins responsible for the enhancement of phagocytosis of liposomes by Kupffer cells and spleen macrophage, respectively. Liver-specific opsonin is a heat-stable macromolecule which on heating or on freezing and thawing exhibits enhanced opsonic activity. Serum also contains a dialysable factor which inhibits its opsonic activity. On the other hand, the spleen-specific opsonin is a heat-labile macromolecule which is sensitive to freezing and thawing and requires a dialysable serum co-factor for its optimum opsonic activity on spleen macrophages. Removal of this factor from serum brings about an irreversible conformational change in the opsonin. Evidence suggests that the spleen-specific opsonin may be composed of more than one different opsonin molecule. It is suggested that the serum factor(s) that inhibits liver-specific opsonic activity and enhances the spleen-specific activity may not be the same molecule, but in both the cases the factor(s) may mediate its function by modifying the process of the opsonisation of liposomes or by influencing the interaction of the opsonised liposomes with the respective cells. We propose that purification of the organ-specific opsonins may provide an opportunity to target drug carriers selectively to a specific organ of the reticuloendothelial system, and help us to evaluate their role in the altered opsonin states known to exist in certain diseases.

Animals↗

PubMed1989

Serum opsonins and phagocytosis of saturated and unsaturated phospholipid liposomes.

Recently we reported that serum contains opsonins specific for hepatic and splenic phagocytic cells and that these opsonins have different properties and affinities for cholesterol-rich and cholesterol-free egg phosphatidylcholine liposomes (Moghimi, S.M. and Patel, H.M. (1988) FEBS Lett. 233, 143-147). In the present report we investigate the affinity of these opsonins for the liposomes prepared from sphingomyelin and saturated phospholipids, as measured by their effect on the uptake of these liposomes by hepatic and splenic phagocytic cells. Results presented here suggest that neither liver- nor spleen-specific opsonins have affinity for sphingomyelin or saturated phospholipid liposomes since serum fails to enhance their uptake in liver or splenic cells. On the contrary, these liposomes attract serum dysopsonins which inhibit their uptake by liver cells. Inclusion of cholesterol in these liposome preparations enhances their uptake in splenic cells but not in liver cells. It is suggested that fluidity and hydrophobicity of liposomal membranes play an important role in attracting the right opsonins which determine their phagocytic fate.

Animals↗

PubMed1988

Tissue specific opsonins for phagocytic cells and their different affinity for cholesterol-rich liposomes.

In accordance with the finding of our in vivo experiments reported earlier [(1983) Biochim. Biophys. Acta 761, 142-157; (1986) Biochim. Biophys. Acta 888, 184-190], the results of in vitro experiments show that Kupffer cells avidly take up cholesterol-poor but not cholesterol-rich liposomes, whereas splenic phagocytic cells take up preferentially cholesterol-rich rather than cholesterol-poor liposomes in the presence of serum. Evidence presented here suggests that serum contains opsonins specific for hepatic and splenic phagocytic cells and these opsonins have different affinities for cholesterol-rich and cholesterol-poor liposomes.

Adsorption↗

PubMedDate not supplied

Liposome recognition by resident and newly recruited murine liver macrophages.

The evidence in this communication indicate that, unlike resident Kupffer cells, newly recruited liver macrophages (following monocyte migration from the blood to the liver) use complement receptors to recognize and internalize stearylamine-incorporated liposomes. Within two weeks of hepatic residency complement receptors no longer participate in liposome recognition and uptake.

Animals↗

PubMedDate not supplied

Concentration dependent structural ordering of poloxamine 908 on polystyrene nanoparticles and their modulatory role on complement consumption.

Adsorption of poloxamine 908, a tetrafunctional polyethylene oxide (PEO)-polypropylene oxide ethylenediamine block copolymer, onto the surface of monodispersed polystyrene nanoparticles (232 +/- 0.33 nm) follows a bimodal pattern. Initially, the isotherm follows a Langmuir profile with a plateau observable over a very narrow equilibrium poloxamine concentration (0.0018-0.0031 mM). The isotherm then begins to rise again, reaching a final plateau at equilibrium poloxamine concentrations above 0.0089 mM. Similarly, the profile of the adsorbed layer thickness of poloxamine on the surface of nanoparticles is bimodal. The first plateau corresponds to a thickness of 4.6 +/- 0.07 nm, which occurs over the same range of poloxamine concentrations as in the initial plateau of the adsorption isotherm. The second plateau corresponds to a thickness of 9.53 +/- 0.32 nm, observable at a minimum poloxamine concentration of 0.0067 mM. By using a calculated radius of gyration of a PEO chain in poloxamine as 3.1 nm, these observations reflect dynamic changes in the arrangement of surface projected PEO chains; a mushroom-like conformation at the first plateau region of the adsorption isotherm, followed by a transition into a brush-like conformation. These conformational changes are also reflected in rheological studies; the apparent viscosity of nanoparticles in which the PEO chains are in mushroom conformation is considerably higher than particles displaying the brush conformation. Further, atomic force microscopy studies (height profile and phase lag measurements) corroborated that the proposed poloxamine concentration dependent transition of surface associated PEO chains from mushroom to brush appearance is conserved when nanoparticles are dried under ambient conditions. Finally, we compared the influence of the surface PEO characteristics on complement consumption in human serum. Our results show complement-activating nature of all poloxamine-coated nanoparticles. However, complement consumption is reduced substantially with particles bearing a minimum of 11448 poloxamine molecules on their surface, thus demonstrating the importance of PEO surface density as well as brush conformation in suppressing complement consumption. This relationship between surface characteristics of poloxamine nanoparticles and their in vivo performance is discussed.

Adsorption↗

PubMedDate not supplied

Current progress and future prospects of liposomes in dermal drug delivery.

Liposomes were introduced first in 1980 for topical drug delivery and since then have attracted considerable interest and generated many speculative claims concerning their potential utility both as a drug carrier and reservoir for controlled release of drugs within various layers of the skin. A number of clinical studies have now demonstrated the superiority of liposomal drug formulations over conventional delivery systems. In this respect, liposomal formulations have been successful in treatment of a number of dermatological diseases and disorders such as psoriasis, mycoses, idiopathic hirsutism and cutaneous infections. This review emphasizes the evaluation of topically applied liposomal formulation both at experimental and clinical levels. Mechanism(s) by which liposomes facilitate deposition of drugs in various layers of the skin is also discussed.

Administration, Topical↗