chapter  8
34 Pages

Intravaginal Drug Delivery

WithJason M. Olbrich, Georgios T. Hilas, Waleed S. W. Shalaby

Women’s health issues continue to generate considerable interest. In recent years, we have seen an escalation in cesarean deliveries in the United States, reaching 30% of all deliveries, less-invasive modalities for nonhormonal contraception and abnormal uterine bleeding, increased awareness for and

CONTENTS

Introduction ......................................................................................................... 141 Anatomy and Physiology of the Vagina .......................................................... 142

Key Histological Features ............................................................................. 142 Vaginal Anatomy ............................................................................................ 143 Vascular and Lymphatic Systems of the Pelvis .......................................... 144 Vaginal Microbiology ..................................................................................... 144

Intravaginal Drug Delivery ............................................................................... 146 Drug Absorption ............................................................................................ 147 Drug Disposition after Vaginal Administration ........................................ 149 Mechanisms of Pelvic Drug Distribution ................................................... 152 Pharmacokinetic Modeling of Vaginal Drug Absorption ......................... 153

Current Trends in Intravaginal Drug Delivery ............................................... 155 Labor Induction .............................................................................................. 155 Hormone Replacement Therapy .................................................................. 156 Contraception ................................................................................................. 157 Infertility .......................................................................................................... 158 Infectious Diseases ......................................................................................... 159 Gynecologic Oncology................................................................................... 163

Future Perspectives: Intravaginal Vaccine Development.............................. 164 HPV as Promoter or Inducer of Cervical Dysplasia and Cancer ............ 164 Vaccine Development for Cervical Cancer and Dysplasia ....................... 165

Conclusions .......................................................................................................... 166 Acknowledgments .............................................................................................. 167 References ............................................................................................................. 167

management of sexually transmitted diseases, availability of vaccines to prevent HPV (human papilloma virus) transmission (the etiology of cervical dyplasia and cancer), as well as increased options to treat urinary incontinence (stress and mixed incontinence), pelvic prolapse, menopause, and gynecologic cancers. While oral, intravenous, and transdermal routes of drug administration have been heavily leveraged, intravaginal drug delivery has made only modest strides. Interestingly, there are many instances for which intravaginal drug delivery may be more suitable and ef€cacious. For example, it has been postulated and observed that therapeutic targeting to the reproductive tract may be more ef€cient through the intravaginal route. Therefore, elevated drug levels may be achieved at a fraction of the systemic dose and toxicity. The rich vascular supply of the vaginal, paravaginal, and parametrial tissues represents a rapid portal of entry when systemic drug levels are also desired without the €rst-pass hepatic metabolism seen with oral drug delivery.