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Featured researches published by Suresh Bhatia.


Biochimica et Biophysica Acta | 1997

Enhancement of the in vivo circulation lifetime of l-α-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization

Patrick L. Ahl; Suresh Bhatia; Paul Meers; Patricia Roberts; Rachel Stevens; Richard Dause; Walter Perkins; Andrew S. Janoff

Incorporation of N-(omega-carboxy)acylamido-phosphatidylethanolamines (-PEs) into large unilamellar vesicles (LUVs) of L-alpha-distearoylphosphatidylcholine (DSPC) was found to dramatically increase the in vivo liposomal circulation lifetime in rats, reaching a maximal effect at 10 mol.% of the total phospholipid. Neither pure DSPC liposomes nor those with the longest circulating derivative, N-glutaryl-dipalmitoylphosphatidylethanolamine (-DPPE), were found to significantly bind complement from serum. Therefore, the relatively short circulation time of pure DSPC liposomes did not appear to be related to greater complement opsonization leading to uptake by the reticuloendothelial system. However, N-(omega-carboxy)acylamido-PEs were particularly efficient inhibitors of a limited aggregation detected for pure DSPC liposomes. The aggregation tendency of DSPC liposomes incorporating various structural analogs of N-glutaryl-DPPE correlated inversely with the circulation lifetimes. Therefore, it is concluded that such PE derivatives enhance the circulation time by preventing liposomal aggregation and avoiding a poorly understood mechanism of clearance that is dependent on size but is independent of complement opsonization. At high concentrations of N-glutaryl-DPPE (above 10 mol.%), the liposomes exhibited strong complement opsonization and were cleared from circulation rapidly, as were other highly negatively charged liposomes. These data demonstrate that both the lack of opsonization and the lack of a tendency to aggregate are required for long circulation. Liposomal disaggregation via N-(omega-carboxy)acylamido-PEs yields a new class of large unilamellar DSPC liposomes with circulation lifetimes that are comparable to those of sterically stabilized liposomes.


Biochimica et Biophysica Acta | 1997

STABILITY OF ASSOCIATION OF 1-O-OCTADECYL-2-O-METHYL-SN-GLYCERO-3-PHOSPHOCHOLINE WITH LIPOSOMES IS COMPOSITION DEPENDENT

Eric Mayhew; Imran Ahmad; Suresh Bhatia; Richard Dause; Julius Filep; Andrew S. Janoff; Elizabet Kaisheva; Walter Perkins; Yan Zha; J. Craig Franklin

The ether lipid, 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), has anticancer activity, but it has serious side-effects, including hemolysis, which prevent its optimal use. We surmised if ET-18-OCH3 could be stably associated with liposomes, less free ET-18-OCH3 would be available for lytic interaction with red cells. Liposome composition variables investigated included acyl chain saturation, phospholipid head group and mole ratio of Chol and ET-18-OCH3. It was found that attenuation of hemolysis was strongly liposome composition dependent. Some ET-18-OCH3 liposome compositions were minimally hemolytic. For example, whereas the HI5 (drug concentration required to cause 5% human red cell lysis) was 5-6 microM for free ET-18-OCH3, it was approximately 250 microM for DOPC (dioleoylphosphatidylcholine):Chol (cholesterol):DOPE-GA (glutaric acid derivatized DOPE):ET-18-OCH3, (4:3:1:2) and 640 microM for DOPE (dioleyolphosphatidylethanolamine):Chol:DOPE-GA:ET-18-OCH3 (4:3:1:2) liposomes. Efflux of carboxyfluorescein (CF) from liposomes and Langmuir trough determinations of mean molecular area of lipids in monolayers (MMAM) were used as indicators of membrane packing and stability. Incorporation of ET-18-OCH3 in liposomes reduced the MMAM. Reduction in CF permeation was correlated with reduction in hemolysis. The most stable liposomes included components, such as cholesterol, DOPC and DOPE, which have complementary shapes to ET-18-OCH3.


Archive | 1996

Hydrophobic taxane derivatives

Eric Mayhew; J. Craig Franklin; Suresh Bhatia; Paul A. Harmon; Andrew S. Janoff


Archive | 1998

Etherlipid-containing multiple lipid liposomes

Eric Mayhew; Andrew S. Janoff; Imran Ahmad; Suresh Bhatia


Archive | 1994

Reduction of liposome-induced adverse physiological reactions

Patrick L. Ahl; Suresh Bhatia; Sharma R. Minchey; Andrew S. Janoff


Archive | 1998

Preparation of pharmaceutical compositions containing etherlipid-containing multiple lipid liposomes

Eric Mayhew; Andrew S. Janoff; Imran Ahmad; Suresh Bhatia


Archive | 1995

Ether lipid liposomes and their therapeutic use

Eric Mayhew; Andrew S. Janoff; Imran Ahmad; Suresh Bhatia


Archive | 1996

Preparation of liposomal taxanes

Eric Mayhew; J. Craig Franklin; Suresh Bhatia; Paul A. Harmon; Andrew S. Janoff


Archive | 1997

Synthesis of hydrophobic taxane derivatives

Eric Mayhew; J. Craig Franklin; Suresh Bhatia; Paul A. Harmon; Andrew S. Janoff


Archive | 1996

Multilipid component ether lipid liposomes

Eric Mayhew; Andrew S. Janoff; Imran Ahmad; Suresh Bhatia

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