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Biomedical subjects

M M Gaspar

Publications and source records attributed to M M Gaspar.

6 recordsLinked to original sources
PubMed2003

Design and characterization of enzymosomes with surface-exposed superoxide dismutase.

Superoxide dismutase (SOD) was chemically modified by covalent linkage of fatty acid chains to the accessible epsilon-amino groups of the enzyme. This acylation method gave rise to a different enzyme entity (Ac-SOD) as evidenced by different physicochemical properties such as octanol/water partition coefficient and isoelectric point (pI) as compared to SOD. Ac-SOD was incorporated in conventional and long-circulating liposomes (LCL) and characterized in terms of incorporation efficiency, protein to lipid ratio (Prot/Lip), enzymatic activity retention and zeta potential. The observation that Ac-SOD liposomes present enzymatic activity on their external surface indicates that these formulations can act independent of rate and extent of enzyme release as required in case of SOD liposomes. The decrease of superficial charge of liposomal formulations containing Ac-SOD, as compared to SOD liposomes, may be related to the negatively charged enzyme molecules localized on the liposome surface. The comparative characterization of Ac-SOD and SOD liposomal formulations evidenced that the two enzyme forms differ substantially regarding their intraliposomal location: SOD tends to be localized in the internal aqueous spaces, whereas Ac-SOD is expected to be localized in the lipid bilayers of the liposomes, partially buried into the outer surface and exposed to the external medium. These liposomal structures with surface-exposed SOD were designated as Ac-SOD enzymosomes. The properties of these enzymosomes may influence the therapeutic effect, as the release of the enzyme from extravasated vesicles is no longer a necessary requirement for achieving dismutating activity within the inflamed target site.

Acylation↗
PubMed2000

Therapeutic efficacy of liposomal rifabutin in a Mycobacterium avium model of infection.

Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied. The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of infection with a virulent Mycobacterium avium strain (strain P1581) and was compared with that of free rifabutin. The influences of the size of the liposomal rifabutin formulation, the administered doses, and the treatment schedules on the evolution of infection were studied. Two types of treatment schedules were assayed: therapeutic and prophylactic. The therapeutic treatment started 2 weeks after infection, while the prophylactic treatment began 1 day before the experimental infection with mycobacteria. Incorporation of rifabutin in liposomes resulted in a significant enhancement of activity against M. avium infection compared to that of rifabutin in the free form in both schedules. These results demonstrate that liposomal formulations of antibiotics such as rifabutin may be effective for the treatment or prophylaxis of infectious diseases.

Animals↗
PubMed1996

Biological characterization of L-asparaginase liposomal formulations.

The biological properties of preselected liposomal formulations of L-asparaginase (L-ASNase) were studied. Pharmacokinetics studies showed that encapsulation in large liposomes (sDRV; median diameter 1,249 nm) decreased the circulation time of the enzyme, whereas encapsulation in small liposomes (VET: median diameter 158-180 nm) prolonged it by a factor of up to 10. Liposome encapsulation in either VET or sDRV prevents the induction of anti-asparaginase antibodies and mitigates the anaphylatic reaction, as no death occurred in animals presensitized and challenged with liposomal formulation, in contrast to animals treated with the free enzyme. The antitumor activity was also enhanced by liposome encapsulation. The survival of animals bearing P1534 tumors was prolonged by a factor of 2 after treatment with selected liposomal formulations as compared with free enzyme.

Animals↗
PubMed1989

Persistent peripheral airway obstruction in children with severe asthma.

We reviewed pulmonary function data on 447 children with the diagnosis of asthma, who were studied in our laboratory over a 6-year interval. We found 19 with evidence of consistent airway obstruction. Two patients who had obvious causes for persistent obstruction were excluded. Seven of the remaining 17 patients consented to further studies. In six of the seven patients studied, flow rates at low lung volumes were severely depressed and remained unchanged after 2 weeks of vigorous "inpatient" therapy. No clinical benefit was apparent. One patient had relentlessly worse disease and died of his asthma. The autopsy revealed changes characteristic of asthma. We conclude that some children with severe asthma have persistent and severe peripheral airway obstruction. These findings challenge the current paradigm that asthma in children is a completely "reversible" illness. Long-term follow-up of children with persistent chronic obstruction may clarify the question of childhood origin of adult lung disease.

Adolescent↗