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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 tenofovir release rates in vitro, to matrix sublimation rates, for microbicide incorporated within a series of (a) rapidly subliming solids and (b) slowly subliming solids. Each plotted point represents a mean ± SEM (N = 4).
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Fig2: Comparison of tenofovir release rates in vitro, to matrix sublimation rates, for microbicide incorporated within a series of (a) rapidly subliming solids and (b) slowly subliming solids. Each plotted point represents a mean ± SEM (N = 4).

Mentions: Use of subliming solids for drug delivery can also provide a broad available range of microbicide release rates and durations. Figure 2a and b demonstrates that under employed in vitro conditions, appropriate choice of matrix material can achieve constant rates of both matrix sublimation and concomitant tenofovir release over durations as short as hours (Fig. 2a) to as long as several months (Fig. 2b). Comparison of data represented by filled and open symbols in both Fig. 2a and b also conclusively demonstrates that the rate of microbicide exposure/release is identical to the rate at which a given matrix sublimes. This study has shown through the above in vitro demonstration of zero-order release for three dissimilar drug substances, incorporated into five different subliming matrices, that volatile water-insoluble organic solids hold promise as a multi month constant release rate delivery system for potentially any number of intravaginally administered HIV-1 microbicides.Fig. 2


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 tenofovir release rates in vitro, to matrix sublimation rates, for microbicide incorporated within a series of (a) rapidly subliming solids and (b) slowly subliming solids. Each plotted point represents a mean ± SEM (N = 4).
© Copyright Policy
Related In: Results  -  Collection

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

Fig2: Comparison of tenofovir release rates in vitro, to matrix sublimation rates, for microbicide incorporated within a series of (a) rapidly subliming solids and (b) slowly subliming solids. Each plotted point represents a mean ± SEM (N = 4).
Mentions: Use of subliming solids for drug delivery can also provide a broad available range of microbicide release rates and durations. Figure 2a and b demonstrates that under employed in vitro conditions, appropriate choice of matrix material can achieve constant rates of both matrix sublimation and concomitant tenofovir release over durations as short as hours (Fig. 2a) to as long as several months (Fig. 2b). Comparison of data represented by filled and open symbols in both Fig. 2a and b also conclusively demonstrates that the rate of microbicide exposure/release is identical to the rate at which a given matrix sublimes. This study has shown through the above in vitro demonstration of zero-order release for three dissimilar drug substances, incorporated into five different subliming matrices, that volatile water-insoluble organic solids hold promise as a multi month constant release rate delivery system for potentially any number of intravaginally administered HIV-1 microbicides.Fig. 2

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