Abstract
Approaches for effective and sustained drug delivery to the female reproductive tract (FRT) for treating a range of gynaecological conditions remain limited. The development of versatile delivery platforms, such as soluble gels (sol–gels) coupled with applicators/devices, holds considerable therapeutic potential for gynaecological conditions. Sol–gel systems, which undergo solution-to-gel transition, triggered by physiological conditions such as changes in temperature, pH, or ion composition, offer advantages of both solution- and gel-based drug formulations. Furthermore, they have potential to be used as a suitable drug delivery vehicle for other novel drug formulations, including micro- and nano-particulate systems, enabling the delivery of drug molecules of diverse physicochemical character. We provide an anatomical and physiological perspective of the significant challenges and opportunities in attaining optimal drug delivery to the upper and lower FRT. Discussion then focuses on attributes of sol–gels that can vastly improve the treatment of gynaecological conditions. The review concludes by showcasing recent advances in vaginal formulation design, and proposes novel formulation strategies enabling the infusion of a wide range of therapeutics into sol–gels, paving the way for patient-friendly treatment regimens for acute and chronic FRT-related conditions such as bacterial/viral infection control (e.g., STDs), contraception, hormone replacement therapy (HRT), infertility, and cancer.
Highlights
Recent advances in pharmaceutical research and development have drawn considerable attention towards developing more effective, patient-friendly, and clinician-endorsed treatment options for conditions of the female reproductive tract (FRT)
The highly variable anatomical and physiological features of the FRT make the therapeutic outcome highly challenging using currently available conventional methods of vaginal drug delivery system (VDDS). This has led to an increased demand for novel drug delivery techniques that are capable of addressing the limitations of conventional VDDSs, including vaginal leakage, lower drug residence time, and lower patient compliance and adherence to the treatment regimen
Sol–gel technology, through the utilisation of “smart” polymers possessing stimuli-responsive and mucoadhesive characteristics, plays a promising role in the safe and efficient delivery of diverse drug molecules in a controlled and sustained manner. This formulation technology may be a carrier for other novel drug delivery platforms including microencapsulation, nanotechnology, liposomes, micro-emulsions, inclusion complexations, and drug-eluting fibres to overcome their limitations raised in the absence of suitable drug delivery vehicles, resulting in the successful delivery of drug molecules of diverse nature, which would otherwise have not been delivered effectively using conventional formulation approaches
Summary
Recent advances in pharmaceutical research and development have drawn considerable attention towards developing more effective, patient-friendly, and clinician-endorsed treatment options for conditions of the FRT. Effective VDD is challenged by the highly variable anatomical, physiological, and microbiological features of the FRT, which transition over a patient’s lifetime, posing a great challenge to formulation scientists where catering to the varied needs of patients can be effectively met In this regard, various conventional formulations (e.g., creams and pessaries), administered vaginally, result in limited delivery success, due to the physiological clearing mechanism of the vagina, which results in premature leakage and sub-therapeutic outcomes. To this end, this review provides a comprehensive analysis of sol–gel systems to achieve the desired therapeutic outcomes for a range of gynaecological conditions that have not yet been effectively addressed using conventional dosage forms. The key databases used to gather material for this review were Science Direct, PubMed, and Web of Science, with only peer-reviewed articles published exclusively in English included
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