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Development and Characterization of Bioadhesive Vaginal Films of Sodium Polystyrene Sulfonate (PSS), a Novel Contraceptive Antimicrobial Agent

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Purpose.

Polystyrene sulfonate (PSS) is a novel noncytotoxic antimicrobial contraceptive agent. A gel formulation of PSS was found safe for vaginal administration in phase I clinical trials. The purpose of the current study was to develop and evaluate novel bioadhesive vaginal film formulations of PSS.

Methods.

PSS films were prepared by solvent evaporation and optimized for various physical, mechanical, and aesthetic properties. Further, films were evaluated for various biological activities and safety.

Results.

Vaginal films containing 300 mg PSS per unit have been developed, using generally regarded as safe (GRAS) listed excipients. The films are colorless, transparent, thin, soft, and tough, dissolve rapidly in physiologic fluid to form a smooth, viscous and bioadhesive solution that could be retained in the vagina for prolonged intervals. Sperm function inhibition (hyaluronidase and cervical mucus penetration) and antimicrobial activities against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) by PSS films were found comparable to PSS. Also, films did not inhibit normal vaginal microflora (Lactobacillus) and were noncytotoxic as indicated by negligible sperm immobilization and cytotoxicity to host cell assays.

Conclusions.

Rapidly dissolving bioadhesive vaginal film formulation of PSS with desired physical, mechanical, aesthetic, and biological properties is a suitable candidate vaginal microbicide for prevention of sexually transmitted disease (STDs) and is ready for toxicological and clinical evaluation.

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Abbreviations

AIDS:

acquired immunodeficiency syndrome

ANOVA:

analysis of variance

AUC:

area under curve

DSC:

differential scanning calorimetry

GPC:

gel permeation chromatography

GRAS:

generally regarded as safe

HEC:

hydroxyethyl cellulose

HIV:

human immunodeficiency virus

HPMC:

hydroxypropylmethyl cellulose

HPV:

human papilloma virus

HSV:

herpes simplex virus

IC50:

inhibitory concentration at 50% level

IC99.9:

inhibitory concentration at 99.9% level

MW:

molecular weight

N-9:

nonoxynol-9

PEG:

polyethylene glycol

PFU:

plaque forming unit

PG:

propylene glycol

PSS:

polystyrene sulfonate

PVA:

polyvinyl alcohol

RH:

relative humidity

SD:

standard deviation

SEM:

standard error mean

SNK test:

Student-Newman-Keuls test

STDs:

sexually transmitted diseases

SVFM:

modified simulated vaginal fluid

TGA:

thermogravimetric analysis

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Punjab, 160062, India

    Sanjay Garg & Alka Garg

  2. School of Pharmacy, The University of Auckland, Private Bag, 92-019, Auckland, New Zealand

    Kavita Vermani

  3. TOPCAD, Rush Presbyterian St. Luke’s Medical Center, Chicago, 60612, Illinois, USA

    Robert A. Anderson & Lourens J. D. Zaneveld

  4. Contraception Research and Development Program (CONRAD), Arlington, Virginia, 22209, USA

    William B. Rencher

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  1. Sanjay Garg
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  2. Kavita Vermani
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  3. Alka Garg
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  4. Robert A. Anderson
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  6. Lourens J. D. Zaneveld
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Correspondence to Sanjay Garg.

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Garg, S., Vermani, K., Garg, A. et al. Development and Characterization of Bioadhesive Vaginal Films of Sodium Polystyrene Sulfonate (PSS), a Novel Contraceptive Antimicrobial Agent. Pharm Res 22, 584–595 (2005). https://doi.org/10.1007/s11095-005-2490-1

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