Block Copolypeptide Nanoparticles for the Delivery of Ocular Therapeutics

Abstract

Self‐assembling block copolypeptides were prepared by sequential ring‐opening polymerization of N‐carboxyanhydride (NCA) derivatives of γ‐benzyl‐L‐glutamic acid and ε‐carbobenzyloxy‐L‐lysine, followed by selective deprotection of the benzyl glutamate block. The synthesized polymers had number average molecular weights close to theoretical values, and had low dispersities (ĐM = 1.15–1.28). Self‐assembly of the amphiphilic block copolymers into nanoparticles was achieved using the “solvent‐switch” method, whereby the polymer was dissolved in THF and water and the organic solvent removed by rotary evaporation. The type of nanostructures formed varied from spherical micelles to a mixture of spherical and worm‐like micelles, depending on copolymer composition. The spherical micelles had an average diameter of 43 nm by dynamic light scattering, while the apparent diameter of the mixed phase system was around 200nm. Reproducibility of nanoparticle preparation was demonstrated to be excellent; almost identical DLS traces were obtained over three repeats. Following qualitative dye‐solubilization experiments, the nanoparticles were loaded with the ocular anti‐inflammatory drug dexamethasone. Loading efficiency of the nanoparticles was 90% and the cumulative drug release was 94% over 16 d, with a 20% burst release in the first 24 h.

Polypeptidic Micelles Stabilized with Sodium Alginate Enhance the Activity of Encapsulated Bedaquiline

“…The amphiphilic structures were obtained by deprotection of the benzyl ester moieties by basic hydrolysis using KOH in THF with subsequent purification by dialysis. This purification step enabled us to perfectly remove the reagents and the organic solvent and was suitable for both polymer lengths.…”

“…In the work presented here we aimed at demonstrating how alginate can be used as coating to stabilize polypeptidic micelles and how it can remarkably decrease the release of a hydrophobic drug encapsulated within their hydrophobic core. As hydrophobic block we have chosen poly(benzyloxycarbonyl lysine) for its good encapsulation properties of hydrophobic drugs . Bedaquiline (BQ) was selected as lipophilic drug based on its importance regarding the treatment of multidrug‐resistant (MDR) tuberculosis (TB).…”

Avoiding the Pitfalls of siRNA Delivery to the Retinal Pigment Epithelium with Physiologically Relevant Cell Models

“…Cationic micelles were prepared by dissolving the amphiphilic polypeptide block copolymer PBE 30 -b-PK 30 [32] in nuclease-free water at a stock concentration of 1 mg/mL. Then, the siRNA and the micellar solution were both diluted in 10 mM HEPES (pH 7.2), mixed together, and incubated at room temperature for at least 20 min to form polyplexes.…”

Stimuli‐Triggered Sol–Gel Transitions of Polypeptides Derived from α‐Amino Acid N‐Carboxyanhydride (NCA) Polymerizations

“…[22] The primary amine hydrochloride significantly decreasedt he basicity of the initiator and inhibited the AMM pathway. [25] Mostr ecently,Z hao et al developed af ast and living NCA polymerization methodology by the incorporation of both primary and secondary or tertiarya mines into one initiation system through an accelerateda mine mechanism through monomer activation (AAMMA). [24] This novel initiator significantly reduced polymerization times and afforded precise control over polypeptide structures, whichr esulted from the unexpected formation of trimethylsilyl carbamate (TMS-CBM) end groupsi nb oth initiation and propagation steps.…”

“…In later work, otherN -TMS amine based initiators were also developed to introduce functional groups for further modification,w hile maintaining the living features of NCA ROPs. [25] Mostr ecently,Z hao et al developed af ast and living NCA polymerization methodology by the incorporation of both primary and secondary or tertiarya mines into one initiation system through an accelerateda mine mechanism through monomer activation (AAMMA). [26] Instead of competition between polymerizations initiated from diverse amines,t he secondaryo rt ertiary amines activated NCA monomers through hydrogen bonding to facilitate the initiation and propagation steps of primary-amine-initiated polymerizations, resultingi nw ell-definedpolypeptides.…”