Engineering, on-demand manufacturing, and scaling-up of polymeric nanocapsules.

José Crecente‐Campo,María José Alonso

doi:10.1002/btm2.10118

Abstract

Polymeric nanocapsules are versatile delivery systems with the capacity to load lipophilic drugs in their oily nucleus and hydrophilic drugs in their polymeric shell. The objective of this work was to expand the technological possibilities to prepare customized nanocapsules. First, we adapted the solvent displacement technique to modulate the particle size of the resulting nanocapsules in the 50–500 nm range. We also produced nanosystems with a shell made of one or multiple polymer layers i.e. chitosan, dextran sulphate, hyaluronate, chondroitin sulphate, and alginate. In addition, we identified the conditions to translate the process into a miniaturized high‐throughput tailor‐made fabrication that enables massive screening of formulations. Finally, the production of the nanocapsules was scaled‐up both in a batch production, and also using microfluidics. The versatility of the properties of these nanocapsules and their fabrication technologies is expected to propel their advance from bench to clinic.

Highlights

Nanocapsules (NCs) are nanometric systems with an inner core and an external shell
Our group extended the application of this technology to the production of NCs with a Abbreviations: Alg, Alginate; chondroitin sulfate (ChS), Chondroitin sulphate; CM-β-glucan, Carboxymethyl-β-glucan; CS, Chitosan; CTAB, Hexadecyltrimethylammonium bromide; dynamic light scattering (DLS), Dynamic light scattering; dextran sulphate (DS), Dextran sulphate; field emission scanning electron microscopy (FESEM), Field emission scanning electron microscopy; HA, Hyaluronate; high-throughput screening (HTS), High-throughput screening; LbL, Layer-by-layer; Lec, lecithin; Mw, Molecular weight; NC, Nanocapsule; NE, Nanoemulsion; P407, poloxamer 407; PACA, Polyisobutylcyanoacrylate; PCL, Poly-ε-caprolactone; polydispersity index (PDI), Polydispersity index; PLA, Poly-(D,L-lactide); STEM, Scanning transmission electron microscope; T80, Tween 80; TPGS, Dα-Tocopherol polyethylene glycol 1,000 succinate hydrophobic shell, that is, poly-ε-caprolactone (PCL) NCs,[3,4,5] and a variety of hydrophilic polymer shells consisting of chitosan (CS),[6] hyaluronic acid,[7] poly-L-asparagine,[8] polyglutamic acid,[9] polyarginine,[10] and protamine.[11]
The lipids are dissolved in a solvent phase, which spontaneously forms NCs when poured into a nonsolvent phase

Summary

Introduction

Nanocapsules (NCs) are nanometric systems with an inner core and an external shell. Depending on their composition, NCs have been named as lipid NCs, consisting of an oily core stabilized by PEGylated amphiphilic molecules; and polymeric NCs, when the oily nucleus is stabilized by a polymeric shell. Al-Kouri et al described in 1986 the first polymeric NCs, made of polyisobutylcyanoacrylate (PACA).[1] In 1989, Fessi et al reported the preparation of poly-(D,L-lactide) (PLA) NCs by the solvent-displacement technique.[2] Subsequently, our group extended the application of this technology to the production of NCs with a Abbreviations: Alg, Alginate; ChS, Chondroitin sulphate; CM-β-glucan, Carboxymethyl-β-glucan; CS, Chitosan; CTAB, Hexadecyltrimethylammonium bromide; DLS, Dynamic light scattering; DS, Dextran sulphate; FESEM, Field emission scanning electron microscopy; HA, Hyaluronate; HTS, High-throughput screening; LbL, Layer-by-layer; Lec, lecithin; Mw, Molecular weight; NC, Nanocapsule; NE, Nanoemulsion; P407, poloxamer 407; PACA, Polyisobutylcyanoacrylate; PCL, Poly-ε-caprolactone; PDI, Polydispersity index; PLA, Poly-(D,L-lactide); STEM, Scanning transmission electron microscope; T80, Tween 80; TPGS, Dα-Tocopherol polyethylene glycol 1,000 succinate hydrophobic shell, that is, poly-ε-caprolactone (PCL) NCs,[3,4,5] and a variety of hydrophilic polymer shells consisting of chitosan (CS),[6] hyaluronic acid,[7] poly-L-asparagine,[8] polyglutamic acid,[9] polyarginine,[10] and protamine.[11] Due to their lipidic core, NCs were, originally, conceived as suitable carriers for lipophilic drugs.

Objectives

Methods

Results

Conclusion