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Antimicrobial susceptibility of microneedle enabled vaginal drug delivery systems

Terrmin

HT23

Beskrivning

Background
More than 70% of women are prone to vaginal microbial infections, predominant ones being bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) (1)(2).. The recurrent nature of these infections calls for more efficient treatment strategies that can increase drug retention time and offer a sustained drug release over a longer period of time. Intravaginal drug delivery, targeting local action, bypasses the usual barriers as seen in oral administration, such as the hepatic first pass effect or gastrointestinal degradation. Additionally, advanced strategies can offer sufficient drug concentrations at the local target site, without having an off-target effect, as seen in the systemic route (3). Anti-microbial compounds (Clotrimazole, Amphotericin B, Itraconazole, Metronidazole) that are commonly used to treat against vaginal infections are lipophilic and belong to the BCS (Biopharmaceutical Classification System) class II or IV of drugs. Such drugs need lipid-based formulations as drug delivery vehicles. Different types of nanocarriers have been explored as drug delivery vehicles against anti-microbial infections, such as nanoemulsions, liposomes, nanocrystals and nanofibers (4)(5). These nanocarriers can be used to better permeate the vaginal epithelium and to obtain a sustained release of drug. The use of microneedles for vaginal drug delivery, addresses a few major concerns regarding the intravaginal treatment in women (6)(7). Microneedles have greater stability owing to their larger surface area when compared to the nanocarriers alone, incorporating microneedles with nanocarriers would further increase their chances at a sustained release of the drug. Microneedle based drug delivery have been studied quite extensively for transdermal applications (8), only a few studies have explored their use for vaginal drug delivery (9)(10).
The various treatment options available against BV and VCC vary in accordance to age, infection stage/recurrence, pregnancy etc. One of the significant obstacles faced in the clinic is the emergence of resistance against drugs by the several fungal (C. albicans, C. aureus, C. glabrata) and bacterial strains (G. vaginalis), hence a thorough in vitro analysis of the above anti-microbial systems against these strains would help build a more efficient vaginal treatment plan (11).

Aim
To manufacture liposomes and nanoemulsions following a previously optimised protocol and fabricate microneedles with dissolvable tips, incorporated with the lipid nanocarriers. The microneedle system will be tested against the commonly occurring infectious strains (fungal and bacterial) to observe the antimicrobial susceptibility.

Methods
• Literature survey of commonly used anti-microbial drugs against BV and VVC, and the resistance rates among the different microbial strains.
• Produce an Oil in Water (O/W) nanoemulsion using the selected set of lipophilic and hydrophilic excipients. Model drugs will be loaded in to the oil phase.
• Produce drug loaded liposomes using thin film hydration method.
• Characterization of the nanocarriers for droplet size and zeta potential using Dynamic Light Scattering (DLS).
• Fabrication of microneedles using manual application of polymers on to premade silicone molds.
• Analysis of the drug loading of the nanocarriers and the microneedles using High performance Liquid Chromatography (HPLC) analysis.
• Testing of the antimicrobial effect of the nanocarriers and microneedles against the common microbial strains occurring in BV and VVC, using disc diffusion method.

Tasks of master student
• To perform a thorough literature survey of drugs and treatment options against BV and VVC.
• To produce nanocarriers loaded with the antimicrobial drugs of choice.
• To characterize them for droplet size, zeta potential using DLS, and drug recovery using HPLC analysis.
• To fabricate microneedles incorporated with the drug loaded nanocarriers.
• To characterize the microneedles for final drug loading using HPLC analysis.
• To perform antimicrobial and antifungal assays using the disc diffusion method.

Expected results
An efficacious microneedle drug delivery system against targeted infectious strains of BV and VVC.

Huvudområde

Läkemedelsutveckling

Ämne

Läkemedelsformulering och Molekylär galenisk farmaci

Typ

Laborativ studie

Företag

Uppsala universitet

Ort/Plats

Uppsala

Handledarens namn

Alexandra Teleki

Handledarens e-post

alexandra.teleki@farmaci.uu.se

Institution

Institutionen för farmaci

Program

Masterprogram i läkemedelsutveckling

Kurs

Degree project in Drug Discovery and Development 45 c -3FK044

Omfattning/hp

45hp