ABSTRACT
Vaginal atrophy affects up to 57% of post-menopausal women, with symptoms ranging from vaginal burning to dysuria. Estradiol hormone replacement therapy may be prescribed to alleviate these symptoms, though many vaginal products have drawbacks including increased discharge and local tissue toxicity due to their hypertonic nature. Here, we describe the development and characterization of a Pluronic F127-coated estradiol nanosuspension (NS) formulation for improved vaginal estradiol delivery. We compare the pharmacokinetics to the clinical comparator vaginal cream (Estrace) and demonstrate increased delivery of estradiol to the vaginal tissue. We utilized ovariectomized (OVX) mice as a murine model of post-menopausal vaginal atrophy and demonstrated equivalent efficacy in vaginal re-epithelialization when dosed with either the estradiol NS or Estrace cream. Further, we demonstrate compatibility of the estradiol NS with vaginal bacteria in vitro. We demonstrate that a Pluronic F127-coated estradiol NS may be a viable option for the treatment of post-menopausal vaginal atrophy.
ABSTRACT
The first publication of micro- and nanotechnology in medicine was in 1798 with the use of the Cowpox virus by Edward Jenner as an attenuated vaccine against Smallpox. Since then, there has been an explosion of micro- and nanotechnologies for medical applications. The breadth of these micro- and nanotechnologies is discussed in this piece, presenting the date of their first report and their latest progression (e.g., clinical trials, FDA approval). This includes successes such as the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines from Pfizer, Moderna, and Janssen (Johnson & Johnson) as well as the most popular nanoparticle therapy, liposomal Doxil. However, the enormity of the success of these platforms has not been without challenges. For example, we discuss why the production of Doxil was halted for several years, and the bankruptcy of BIND therapeutics, which relied on a nanoparticle drug carrier. Overall, the field of micro- and nanotechnology has advanced beyond these challenges and continues advancing new and novel platforms that have transformed therapies, vaccines, and imaging. In this review, a wide range of biomedical micro- and nanotechnology is discussed to serve as a primer to the field and provide an accessible summary of clinically relevant micro- and nanotechnology platforms.
ABSTRACT
A zinc-carnosine (ZnCar) metal-organic coordination polymer was fabricated in biologically relevant N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid (HEPES) buffer for use as a vaccine platform. In vitro, ZnCar exhibited significantly less cytotoxicity than a well-established zeolitic imidazolate framework (ZIF-8). Adsorption of CpG on the ZnCar surface resulted in enhanced innate immune activation compared to soluble CpG. The model antigen ovalbumin (OVA) was encapsulated in ZnCar and exhibited acid-sensitive release in vitro. When injected intramuscularly on days 0 and 21 in C57BL/6 mice, OVA-specific serum total IgG and IgG1 were significantly greater in all groups with ZnCar and antigen compared to soluble controls. Th1-skewed IgG2c antibodies were significantly greater in OVA and CpG groups delivered with ZnCar for all time points, regardless of whether the antigen and adjuvant were co-formulated in one material or co-delivered in separate materials. When broadly acting Computationally Optimized Broadly Reactive Antigen (COBRA) P1 influenza hemagglutinin (HA) was ligated to ZnCar via its His-tag, significantly greater antibody levels were observed at all time points compared to soluble antigen and CpG. ZnCar-formulated antigen elicited increased peptide presentation to B3Z T cells in vitro and production of IL-2 after ex vivo antigen recall of splenocytes isolated from vaccinated mice. Overall, this work displays the formation of a zinc-carnosine metal-organic coordination polymer that can be applied as a platform for recombinant protein-based vaccines.
