Encapsulated functionalized stereocomplex PLA particles: An effective system to support mucolytic enzymes

Abstract

In this work, the preparation of a novel enzyme carrier based on a polymer multicomponent system was assessed. Indeed, the design of the above system considered several issues that are the need of applying a biodegradable polymer carrier, characterized by a nanometric dimension, thus suitable to diffuse into the dense mucus structure, with functionalities capable of interacting/reacting with enzymes but resistant to enzymatic degradation. The particles were prepared from solutions containing equimolar amount of highmolecular-weight poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) and by applying the nanoprecipitation method. Dynamic Light Scattering (DLS) measurements allowed to establish the optimal preparation conditions to obtain polymer particles characterized by diameters lower than 1 μm, which dimensions were confirmed by Field Emission Scanning Electron Microscope (FE-SEM) analysis. In order to produce surface functionalization, necessary for anchoring enzymes, the stereocomplexed particles, whose structuration was confirmed by Differential Scanning Calorimetry (DSC) measurements, underwent an amminolysis reaction by using a diamine as reactant. The treated particles were characterized by means of FE-SEM, Fourier-Transform Infrared Spectroscopy (FTIR), DLS and zeta potential measurements and their characteristics were compared with those of the neat PLLA/PDLA particles. The degree of functionalization turned out to depend on the applied conditions, it increasing by enhancing the reaction time. The activity of enzymes, i.e. papain and alginate lyase, anchored to the particles , was evaluated by Quartz Crystal Microbalance (QCM) and UV measurements.Moreover, with the aim at exploiting the material for an inhalation administration, a method to encapsulate the enzyme-particles systems was assessed. Conversely to free enzymes, the developed systems were found to be capable of diminishing the viscosity of two hydrogels, ad hoc prepared and based on the main constituents of the real mucus.

Characterization of Nanomaterials by Locally Determining Their Complex Permittivity with Scattering-Type Scanning Near-Field Optical Microscopy

“…60 In the current experiment, we have focused our attention on the quantitative s-SNOM imaging of a specific class of PMCs, namely biopolymeric capsules that can self-degrade in a controlled fashion upon the interaction of an entrapped proteolytic enzyme with the PMC walls. This experiment extends previous recent work, 34 where it was shown by confocal microscopy and AFM how enzymes loaded inside such microcapsules disrupt the microcapsules shell. The investigation and evaluation of the degradative process play a pivotal role for the design of efficient delivery systems; however, considering the dimensions of the microcapsules, and the scale at which degradation cues occur, this process is impossible to be optically investigated in detail with diffraction-limited techniques.…”

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

“…Despite these advantages, many challenges remain for the application of sc-PLA as a drug carrier, including inferior encapsulation efficiency, low stability of hydrophilic drugs and proteins, and the burst release phenomenon. To resolve these issues, various strategies, such as polymerization, self-assembly, surface modification, and polymer grafting, have been studied [ 13 , 14 , 15 , 16 , 17 ]. This review discusses various synthesis and processing methods for the application of sc-PLA as a drug and molecular carrier, and it suggests future directions to stimulate the application of sc-PLA with therapeutic molecules in drug delivery systems and biomedical applications.…”

Layer-by-Layer Cell Encapsulation for Drug Delivery: The History, Technique Basis, and Applications

“…In animal studies, proteases were demonstrated to digest LbL films constructed with dextran and poly(Larginine). Another study took advantage of an enzyme which was put inside LbL films with poly(L-lactide) and poly(D-lactide) to adjust their degradation time [210].…”