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![(A) Arteriography of the uterus, ovaries, fallopian tubes, and upper vaginal segment. With permission from Ref (Belou P. Atlas estereosco'pico de anatomı'a de las arterias del hombre. Tomo III 2da parte. En: Revisión anatómica del sistema arterial (Stereoscopic Atlas of Human Arterial Anatomy. Volume 3; 2nd Part in: Anatomic Revision of Arterial System). Buenos Aires: El Ateneo, 1934:98-119). LIIA, left internal iliac artery; LLVA, lower left vaginal artery; LUA, left uterine artery; MLVA, middle left vaginal artery; MRVA, middle right vaginal artery; RLA, round ligament artery; ROA, right ovarian artery; RUA, right uterine artery; UB, the uterine body; VA, vagina. (B) Cadaveric specimen. Upper and left view of the genital-urinary organs. In the middle sector of the illustration, a thick intrauterine anastomosis can be identified. Below, thick vaginal branches anastomosing with the uterine artery can be observed. LAM, levator ani muscle; LIIA, left internal iliac artery; LIPA, left internal pudendal artery; LLVA, lower left vaginal artery; LTOA, left tubo-ovarian artery; LUA, left uterine artery; OV, ovary; TIA, transmedial inter uterine anastomosis; UVA, uterovaginal anastomosis [54]. Figure license number: 4810031431586.](publication/347913568/figure/fig1/AS:1023051038724096@1620925783920/A-Arteriography-of-the-uterus-ovaries-fallopian-tubes-and-upper-vaginal-segment.jpg)
(A) Arteriography of the uterus, ovaries, fallopian tubes, and upper vaginal segment. With permission from Ref (Belou P. Atlas estereosco'pico de anatomı'a de las arterias del hombre. Tomo III 2da parte. En: Revisión anatómica del sistema arterial (Stereoscopic Atlas of Human Arterial Anatomy. Volume 3; 2nd Part in: Anatomic Revision of Arterial System). Buenos Aires: El Ateneo, 1934:98-119). LIIA, left internal iliac artery; LLVA, lower left vaginal artery; LUA, left uterine artery; MLVA, middle left vaginal artery; MRVA, middle right vaginal artery; RLA, round ligament artery; ROA, right ovarian artery; RUA, right uterine artery; UB, the uterine body; VA, vagina. (B) Cadaveric specimen. Upper and left view of the genital-urinary organs. In the middle sector of the illustration, a thick intrauterine anastomosis can be identified. Below, thick vaginal branches anastomosing with the uterine artery can be observed. LAM, levator ani muscle; LIIA, left internal iliac artery; LIPA, left internal pudendal artery; LLVA, lower left vaginal artery; LTOA, left tubo-ovarian artery; LUA, left uterine artery; OV, ovary; TIA, transmedial inter uterine anastomosis; UVA, uterovaginal anastomosis [54]. Figure license number: 4810031431586.
Source publication
While contraceptive drugs have enabled many people to decide when they want to have a baby, more than 100 million unintended pregnancies each year in the world may indicate the contraceptive requirement of many people has not been well addressed yet. The vagina is a well-established and practical route for the delivery of various pharmacological mo...
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Background
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Introduction:
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Citations
... The amount of pressure required to extrude a given biomaterial ink using a given printing system can be referred to as that system's extrudability [6]. However, most hydrogels are shear-thinning, meaning their viscosities decrease with increasing shear strain [7,8] implying the higher risk of poor shape fidelity. Shape fidelity has been a vague, but important term used to describe the printability of the biomaterials inks. ...
This study focuses on the development of printable biomaterial inks using a bacterial exopolysaccharide (EPS) called polyglucuronic acid (PGU), along with bacterial cellulose (BC) or methylcellulose (MC). The physical, mechanical, and biological properties of the hydrogels originating from these inks were assessed through scanning electron microscope (SEM) imaging, rheological tests, and cytocompatibility assessments. The results demonstrate that incorporating PGU into BC or MC inks enhances the shape fidelity, printability, and rigidity of the resulting 3D-printed hydrogels. Moreover, all crosslinked hydrogels based on PGU and BC or MC exhibited cytocompatibility with fibroblast cells (3T3-L1). These findings highlight the potential of the PGU/BC or MC-based biomaterial inks for various tissue engineering applications, including injectable gels, drug delivery systems, and soft tissue models. Furthermore, the study underscores the potential of using bacterial PGU as an alternative to alginate in biomaterial ink development and 3D printing.
... Furthermore, they are suitable for short time utilization or as adjuvants with other methods. There are four classes of spermicidal agents: surface-active agents, enzyme inhibitors, membrane stabilizing agents, and sulfhydryl binding agents (Jalalvandi et al., 2021). ...
It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X1), terpenes concentration (X2), terpenes type (X3), and chitosan concentration (X4) as independent variables, while their impact was observed for entrapment efficiency percent (Y1; EE%), particle size (Y2; PS), zeta potential (Y3; ZP), and amount of drug released after 6 h (Y4; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for ex-vivo and in-vivo investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive.
... Due to the presence of an extensive network of blood vessels, the vagina is an attractive route of drug delivery for both local and systemic effects. Due to the avoidance of the hepatic first-pass effect, the vagina serves as an effective route for the delivery of hormonal contraceptives and probiotics [4]. A complex interaction of vaginal microbiota, microbial by-products, estrogens, and host factors keeps the vaginal ecosystem in a finely balanced state. ...
... These vaginal dosage forms are associated with several drawbacks, including leakage, messiness, and short residence time, which lead to reduced patient compliance and therapeutic efficacy. Several novel DDS, such as liposomes, microemulsions, Nanoparticles (NPs), Microparticles (MPs), bio-adhesive gels, bio-adhesive films, bio-adhesive tablets, vaginal rings, microneedles, etc., have been investigated for vaginal application in recent years [3][4][5][6] (Fig. 1). Some key advantages of novel systems for vaginal delivery include better mucoadhesiveness, sustained action, and modified drug profiles [7]. ...
The vagina is an essential part of the female reproductive system and offers many potential benefits over conventional drug delivery including a large surface area for drug absorption, relatively low enzymatic activity, avoids first-pass effects, and ease of administration. The vaginal mucosal cavity is an effective route for administering therapeutic agents that are intended both for local and systemic administration. The present review provides a comprehensive overview of recent trends and developments in vaginal drug delivery. Marketed formulations and products under clinical study are also reviewed.
Conclusion: Various novel vaginal delivery systems have been studied in recent years as an effective tool for delivering a range of therapeutic agents to the vagina. These systems offer numerous benefits, including sustained delivery, improved bioavailability, effective permeation, and higher efficacy. The recent focus of the scientific community is on the development of safe and efficient drug delivery systems such as nanoparticles, microparticles, vesicular systems, vaginal rings, microneedles, etc. for vaginal application. Various factors such as the physicochemical properties of the drugs, the volume and composition of the vaginal fluid, the pH of the vaginal fluid, the thickness of the vaginal epithelium, and the influence of sexual intercourse may influence the release of drugs from the delivery system and subsequent absorption from the vaginal route. To date, only limited number of in vivo studies on novel vaginal DDS have been reported. Additionally, drug release kinetics under varying vaginal environments is also not well understood. More research is needed to ensure the suitability, biocompatibility, and therapeutic effectiveness of novel DDS for vaginal delivery. Although numerous strategies and interventions have been developed, clinical translation of these systems remains a challenge. The toxicity of the carrier system is also an important consideration for future clinical applications.
... Weakly acidic drugs (pKa < 5.5, e.g., tenofovir) remain unionised under physiological conditions, while weakly basic drugs (pKa 8.5-10.5, e.g., itraconazole, voriconazole) are ionised in the acidic environment of the lower FRT [77][78][79][80]. However, a fluctuating pH, especially that evident in the vagina, can directly affect drug ionisation, which in turn impacts solubility and ultimately drug absorption. ...
... Hormonal contraceptives based on combined oestrogen and progestin, or progestin alone, are used widely for contraception as well as non-contraceptive purposes such as irregular periods, heavy bleeding, and anaemia, and are available as combined oral contraceptives (COCs), emergency pills, intramuscular depots, subdermal implants, and intrauterine devices [120,121]. Despite the availability of several hormonal vaginal and non-vaginal contraceptives, vaginal contraceptives are gaining in popularity due to the advantages that the vaginal route offers compared to non-vaginal routes [78]. Nevertheless, high costs, side effects such as weight gain, low libido, depression, increased risk of breast cancer, cervical cancer, and venous thromboembolism, the necessity of strict adherence to the dosage regimen of COCs, and the requirement of trained personnel for vaginal use reduce patient compliance [78,121,122]. ...
... Despite the availability of several hormonal vaginal and non-vaginal contraceptives, vaginal contraceptives are gaining in popularity due to the advantages that the vaginal route offers compared to non-vaginal routes [78]. Nevertheless, high costs, side effects such as weight gain, low libido, depression, increased risk of breast cancer, cervical cancer, and venous thromboembolism, the necessity of strict adherence to the dosage regimen of COCs, and the requirement of trained personnel for vaginal use reduce patient compliance [78,121,122]. This has resulted in almost 99 million unplanned pregnancies worldwide annually, highlighting the need for novel controlledrelease contraceptives that can reduce side effects, and so aid in patient compliance and adherence [78,121,122]. ...
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.
... Among these antigens, SP17 was an important antigen in which many researchers worked to elucidate its immunocontraceptive properties (Lea et al., 1997;Diekman and Herr, 1997;O'Donnell et al., 2021;Mirandola et al., 2015). SP10 and SP56 (Bleil and Wassarman, 1990) have also been studied for their role and use in immunocontraception (Frayne and Hall, 1999;Jalalvandi et al., 2021;Naz, 2005;Kerr et al., 1998;Sharma et al., 2017). Other antigens like tNASP (nuclear autoantigenic sperm protein) Nagatomo et al., 2016), FA-1 (Naz and Wolf, 1994 Curtis et al., 2002;Turner et al., 2002;Shideler et al., 2002;Kirkpatrick et al., 1996(Kirkpatrick et al., 1996) (Tumova et al., 2021) Virally vectored zona pellucida Rabbit vertebrate Pests Mouse Produces Follicular damage after immunisation and thus prevent the meeting of sperm and egg for fertilization Hardy et al., 2006;Lloyd et al., 2003;Hardy, 2007;Redwood, 2008(Redwood et al., 2008) McLeod et al., 2008 Gonadotropin-releasing hormone (GnRH) Swine Mouse Horse White-Tailed Deer Stops or lessens the production of LH and FSH hormone, which helps in controlling the gamete production and also the secondary sexual characteristics in both male and female Killian et al., 2006;Miller et al., 2008;Han et al., 2016;Goodwin et al., 2015;Barranco et al., 2015(Madbouly et al., 2021 Pinna et al., 2015 ...
Background
The world population is continuously growing. It has been estimated that half of the world’s population is from the Asian continent, mainly from China and India. Overpopulation may lead to many societal problems as well as to changes in the habitat. Birth control measures are thus needed to control this growth. However, for the last 50–60 years, there have not been any improvements in the field of contraception. Nevertheless, the immunocontraceptive vaccine is an emerging field, and it might be the only replacement for the existing mode of contraception for the next millennium. Sexually transmitted infections (STIs) are frequent, and their transmission rate increases yearly. As antibiotics are the prevailing treatment for this kind of infections, resistance in humans has increased; therefore, having effective antibiotic treatments for STIs is now a concern. Vaccines against STIs are now needed. It is thought that the improvements in the fields of proteomics, immunomics, metabolomics, and other omics will help in the successful development of vaccines.
Objective
To collect and review the literature about recent advancements in immunocontraception and vaccines against sexually transmitted diseases/infections.
Methods
Reliable scientific databases, such as PubMed Central, PubMed, Scopus, Science Direct, and Goggle Scholar, were consulted. Publications bearing important information on targeted antigens/immunogens for contraceptive vaccine design and advancements in vaccine development for STIs were gathered and tabulated, and details were analyzed as per the theme of each study.
Results
Important antigens that have a specific role in fertility have been studied extensively for their contraceptive nature. Additionally, the advancements in the screening for the best antigens, according to their antigenic nature and how they elicit immune responses for an extended period were also studied. Herd immunity for STIs and advancements in the development of vaccines for syphilis, gonorrhea, and herpes simplex virus were also studied and tabulated in this review. An extensive knowledge on STIs vaccines was gained.
Conclusion
This extensive review is aimed to provide insights for active researchers in vaccinology, immunology, and reproductive biology. Advancements in the development of vaccines for different STIs can be gathered as a wholesome report.
... Although being considered alternative, the vaginal route is practical and well-established (dos Jalalvandi et al., 2020). As there are no cells with metabolic enzymes, this route has the advantage of circumventing the first pass effect, common in oral route, which allows the use of lower dosages of drugs, avoiding side effects incidence. ...
Infectious diseases related to the vagina include diseases caused by the imbalance of the vaginal flora and by sexually transmitted infections. Some of these present themselves as a public health problem due to the lack of efficient treatment that leads to their complete cure, and others due to the growing resistance to drugs used in therapy. In this sense, new treatment strategies are desirable, with vaginal administration rout being a great choice since can bypass first-pass metabolism and decrease drug interactions and adverse effects. However, it is worth highlighting limitations related to patient's discomfort at application time. Thereby, the use of poloxamer-based drug delivery systems is desirable due its stimuli-sensitive characteristic. Therefore, the present review reports a brief overview of poloxamer properties, biological behavior and advances in poloxamer applications in controlled drug release systems for infectious diseases related to the vagina treatment and prevention.
Tenofovir disoproxil fumarate (TDF)-loaded bioadhesive chitosan microparticles (CM) were developed by an emulsification internal gelation technique. Among different batches produced, ECH-4 was found to display a high % entrapment efficiency (68.93 ± 1.76%) and sustained drug release of 88.05 ± 0.38% at 24 h. Solid state characterization of ECH-4 employing DSC and PXRD indicated that the TDF existed in an amorphous state as a solid-solid solution in chitosan. Scanning electron microscopy revealed CM of ECH-4 was spherical in shape with a rough surface topography. Laser scattering analysis using Malvern Master sizer indicated that particle size of ECH-4 was in the range of 0.52 ± 0.10 μm to 284.79 ± 21.42 μm with a surface-mean diameter of 12.41 ± 0.06 μm. Ex vivo mucoadhesion studies using rabbit mucosa as a substrate indicated that 10.34 ± 2.08% of CM of ECH-4 was retained at the end of 24 h. The microparticles of ECH-4 were incorporated into dispersible tablets (DT-TCM) intended for intravaginal administration, in view to arrest the pre-exposure transmission of HIV during sexual intercourse. In vitro release from the dispersible tablet (F3) into simulated vaginal fluid (pH 4.5) displayed a sustained release profile of TDF as 89.98 ± 1.61% of TDF was released at 24 h. The in vitro dissolution profile of the DT-TCM was found to be similar to that of TDF loaded CM with the values of f1 (difference factor) and f2 (similarity factor) being 1.52 and 78.02, respectively. Therefore, DT-TCM would be a promising novel drug delivery platform for pre-exposure prophylaxis against HIV.
To understand the mechanism of action of drugs, it is necessary to have a thorough knowledge of different mechanisms identified and established for endogenous ligands/drugs to act. Presently, we are focusing on understanding the basic concepts of pharmacology, different subdivisions of pharmacology, and the two different types of pharmacological studies, namely, “pharmacokinetics and pharmacodynamics.” Basics about the various routes of drug administration and their merits and demerits are important determinants of the drugs biological influences. Pharmacokinetic considerations include the studies regarding absorption, distribution, metabolism, and excretion of the drugs, while the pharmacodynamic considerations involve the basic mechanisms involved in drug action and effects. This chapter discusses the basic concepts of pharmacology, different emerging branches of pharmacology, routes of drug administration, basics about the pharmacokinetics and pharmacodynamics of the drugs, molecular mechanisms of drug action, and different types of receptors and receptor pharmacology.
