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Sustained local delivery of structurally diverse HIV-1 microbicides released from sublimation enthalpy controlled matrices.

Gunaseelan S, Gallay PA, Bobardt MD, Dezzutti CS, Esch T, Maskiewicz R - Pharm. Res. (2012)

Bottom Line: Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo.Durations of release ranging from several days to several months were readily achieved.Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy Loma Linda University, 11175 Campus Street, Chan Shun Pavilion 21018, Loma Linda, California 92350, USA.

ABSTRACT

Purpose: Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance of prophylactic success.

Methods: Tenofovir, emtricitabine, and C5A peptide HIV microbicides were mechanically incorporated into matrices comprising a series of subliming solids. Matrix sublimation rates and drug release rates were measured in three in vitro and one in vivo environments intended to model human vaginal interior. Antiviral activity studies evaluating matrix incorporated microbicides were performed using in vitro cell cultures and human ectocervical explants.

Results: Drug release rates were identical to matrix sublimation rates, and were zero order. Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo. Durations of release ranging from several days to several months were readily achieved. Prolonged duration of anti HIV-1 activity was shown for matrix incorporated microbicides, using ectocervical explant and cell culture models of HIV-1 infection.

Conclusion: Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides.

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Related in: MedlinePlus

Comparison of in vitro (controlled convection) release rates of bC5A, emtricitabine and tenofovir, when incorporated within HMCS (open symbols) or PF-11 matrices (filled symbols). Each plotted point represents a mean ± SEM (N = 4).
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Fig1: Comparison of in vitro (controlled convection) release rates of bC5A, emtricitabine and tenofovir, when incorporated within HMCS (open symbols) or PF-11 matrices (filled symbols). Each plotted point represents a mean ± SEM (N = 4).

Mentions: Zero-order in vitro drug release from constant surface area matrix cylinders, measured by amounts of embedded microbicide particles progressively exposed on matrix pellet surfaces, appears to occur primarily through sublimation mediated surface erosion, with release rates of structurally dissimilar microbicide molecules being equal to the sublimation rate of the matrix into which they were incorporated, and independent of the drugs physicochemical properties (Fig. 1). Release rates of bC5A peptide, FTC and TDF were very similar to each other, in spite of their structural diversity and wide molecular size range, and equal to the sublimation rates of the HMCS or PF-11 matrices within which they were incorporated. This suggests that a particular duration of release was determined by the specific thermodynamic phase change properties of HMCS and PF-11 matrices providing sustained release.Fig. 1


Sustained local delivery of structurally diverse HIV-1 microbicides released from sublimation enthalpy controlled matrices.

Gunaseelan S, Gallay PA, Bobardt MD, Dezzutti CS, Esch T, Maskiewicz R - Pharm. Res. (2012)

Comparison of in vitro (controlled convection) release rates of bC5A, emtricitabine and tenofovir, when incorporated within HMCS (open symbols) or PF-11 matrices (filled symbols). Each plotted point represents a mean ± SEM (N = 4).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3473190&req=5

Fig1: Comparison of in vitro (controlled convection) release rates of bC5A, emtricitabine and tenofovir, when incorporated within HMCS (open symbols) or PF-11 matrices (filled symbols). Each plotted point represents a mean ± SEM (N = 4).
Mentions: Zero-order in vitro drug release from constant surface area matrix cylinders, measured by amounts of embedded microbicide particles progressively exposed on matrix pellet surfaces, appears to occur primarily through sublimation mediated surface erosion, with release rates of structurally dissimilar microbicide molecules being equal to the sublimation rate of the matrix into which they were incorporated, and independent of the drugs physicochemical properties (Fig. 1). Release rates of bC5A peptide, FTC and TDF were very similar to each other, in spite of their structural diversity and wide molecular size range, and equal to the sublimation rates of the HMCS or PF-11 matrices within which they were incorporated. This suggests that a particular duration of release was determined by the specific thermodynamic phase change properties of HMCS and PF-11 matrices providing sustained release.Fig. 1

Bottom Line: Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo.Durations of release ranging from several days to several months were readily achieved.Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy Loma Linda University, 11175 Campus Street, Chan Shun Pavilion 21018, Loma Linda, California 92350, USA.

ABSTRACT

Purpose: Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance of prophylactic success.

Methods: Tenofovir, emtricitabine, and C5A peptide HIV microbicides were mechanically incorporated into matrices comprising a series of subliming solids. Matrix sublimation rates and drug release rates were measured in three in vitro and one in vivo environments intended to model human vaginal interior. Antiviral activity studies evaluating matrix incorporated microbicides were performed using in vitro cell cultures and human ectocervical explants.

Results: Drug release rates were identical to matrix sublimation rates, and were zero order. Differences in matrix material sublimation enthalpies determined drug release and matrix erosion rates in a thermodynamically definable manner, in vitro and in vivo. Durations of release ranging from several days to several months were readily achieved. Prolonged duration of anti HIV-1 activity was shown for matrix incorporated microbicides, using ectocervical explant and cell culture models of HIV-1 infection.

Conclusion: Subliming solid matrices show promise as a delivery system providing multi month intravaginal release of a wide range of HIV-1 microbicides.

Show MeSH
Related in: MedlinePlus