Ocular Delivery of Predatory Bacteria with Cryomicroneedles Against Eye Infection

Abstract

The development of potent antibiotic alternatives with rapid bactericidal properties is of great importance in addressing the current antibiotic crisis. One representative example is the topical delivery of predatory bacteria to treat ocular bacterial infections. However, there is a lack of suitable methods for the delivery of predatory bacteria into ocular tissue. This work introduces cryomicroneedles (cryoMN) for the ocular delivery of predatory Bdellovibrio bacteriovorus (B. bacteriovorus) bacteria. The cryoMN patches are prepared by freezing B. bacteriovorus containing a cryoprotectant medium in a microneedle template. The viability of B. bacteriovorus in cryoMNs remains above 80% as found in long‐term storage studies, and they successfully impede the growth of gram‐negative bacteria in vitro or in a rodent eye infection model. The infection is significantly relieved by nearly six times through 2.5 days of treatment without substantial effects on the cornea thickness and morphology. This approach represents the safe and efficient delivery of new class of antimicrobial armamentarium to otherwise impermeable ocular surface and opens up new avenues for the treatment of ocular surface disorders.

Freezing biological organisms for biomedical applications

“…(C) Cornea thickness before and after treatment every day. Reproduced under terms of the CC‐BY license 37 . Copyright 2021, The Authors, published by John Wiley and Sons.…”

“…In another work of this team, the process was further simplified. 37 The buffer solutions composed of predatory bacteria, glycerol, and PBS were added to the MN mold and then centrifuged to fill up the needle cavities. After some other solutions were added as the base, they were placed at 4°C for the precipitation of bacteria.…”

“…Besides, melanocytes and RFP‐HeLa cells in cryoMNs displayed minimal viability change after 1 month of preservation. In another work of this team, the process was further simplified 37 . The buffer solutions composed of predatory bacteria, glycerol, and PBS were added to the MN mold and then centrifuged to fill up the needle cavities.…”

“…63 To achieve the deep penetration of the predatory bacteria, cryoMNs were used as a topical delivery platform to deliver Bdellovibrio bacteriovorus (B. bacteriovorus) for the treatment of eye infection (Figure 11A). 37 Bacterial viability in cryoMNs could remain above 80% after the long-term cryo-storage. The predatory bacteria encapsulated cryoMNs displayed excellent inhibition effect on gram-negative bacteria.…”

ε‐poly‐L‐lysine‐modified polydopamine nanoparticles for targeted photothermal therapy of drug‐resistant bacterial keratitis

“… 5 , 6 To address these challenges, novel board‐spectrum therapeutic approaches such as metal nanoparticles, nanozymes, cationic species, photothermal therapy (PTT), and photodynamic therapy (PDT) have been investigated. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 …”