pH-controlled drug loading and release from biodegradable microcapsules

doi:10.1016/j.nano.2008.06.004

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 4, Issue 4, December 2008, Pages 302-310

https://doi.org/10.1016/j.nano.2008.06.004 Get rights and content

Abstract

Microcapsules made of biopolymers are of both scientific and technological interest and have many potential applications in medicine, including their use as controlled drug delivery devices. The present study makes use of the electrostatic interaction between polycations and polyanions to form a multilayered microcapsule shell and also to control the loading and release of charged drug molecules inside the microcapsule. Micron-sized calcium carbonate (CaCO₃) particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between sodium carbonate and calcium nitrate tetrahydrate solutions suspended with CS macromolecules. Oppositely charged biopolymers were alternately deposited onto the synthesized particles using electrostatic layer-by-layer self-assembly, and glutaraldehyde was introduced to cross-link the multilayered shell structure. Microcapsules integrated with CS inside the multilayered shells were obtained after decomposition of the CaCO₃ templates. The integration of a matrix (i.e., CS) permitted the subsequent selective control of drug loading and release. The CS-integrated microcapsules were loaded with a model drug, bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA), and it was shown that pH was an effective means of controlling the loading and release of FITC-BSA. Such CS-integrated microcapsules may be used for controlled localized drug delivery as biodegradable devices, which have advantages in reducing systemic side effects and increasing drug efficacy.

Section snippets

Materials

Poly-l-lysine hydrobromide (PLL, MW 150–300 kDa), chondroitin sulfate sodium salt (CS), glycine, sodium carbonate (Na₂CO₃), calcium nitrate tetrahydrate (Ca(NO₃)₂), FITC-BSA, and GA were purchased from Sigma (St. Louis, Missouri). EDTA was obtained from Fisher (Fair Lawn, New Jersey), and quartz slides were purchased from Electron Microscopy Sciences (Hatfield, Pennsylvania). A 0.05 M glycine solution of pH 5.5 was prepared and used throughout this study. PLL (1 mg/mL) and CS (1 mg/mL)

Results

In this study, CaCO₃ microparticles integrated with CS were prepared, and LBL was applied to form multilayered shells on the particles. After dissociation of the CaCO₃ particles, polyelectrolyte microcapsules were obtained, and the integration of CS inside the capsules was intended to alter the physical properties of the capsule interior, which would allow control of subsequent drug loading and release via pH. A model drug, FITC-BSA, was loaded and its release investigated. pH was explored as a

Discussion

Development of biodegradable drug delivery systems with controllable loading and release capabilities is of importance. Despite the progress made in the last couple of years in preparation of polyelectrolyte microcapsules, the control of drug loading and release from polyelectrolyte microcapsules is still a challenging task for researchers in biotechnology and medicine. The present study reports a new strategy to load charged drug molecules in polyelectrolyte microcapsules for triggered or

Acknowledgments

The authors appreciate the use of the confocal laser scanning microscope at the Microscopic Imaging Facilities at West Virginia University Health Sciences Center. The authors also thank Suzanne Smith for proofreading.

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: Financial support from National Aeronautics and Space Administration West Virginia Experimental Program to Stimulate Competitive Research, West Virginia University (WVU) Program to Stimulate Competitive Research, and WVU Senate Grant are acknowledged. No commercial associations, current and within the past 5 years, that might pose a potential, perceived, or real conflict of interest, were reported by the authors of this article.

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Original Article: Drug DeliverypH-controlled drug loading and release from biodegradable microcapsules

Abstract

Section snippets

Materials

Results

Discussion

Acknowledgments

Eur J Pharm Biopharm

Colloids Surfaces A

Colloids Surfaces A

Biosens Bioelectron

Designing materials for biology and medicine

Nature

Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating

Science

Novel hollow polymer shells by colloid-templated assembly of polyelectrolytes

Angew Chem Int Ed. Engl

Release mechanisms for polyelectrolyte capsules

Chem Soc Rev

Tailor-made polyelectrolyte microcapsules: from multilayers to smart containers

Angew Chem Int Ed Engl

Polyelectrolyte complexes and layer-by-layer capsules from chitosan/chitosan sulfate

Biomacromolecules

Loading the multilayer dextran sulfate/protamine microsized capsules with peroxidase

Biomacromolecules

Self-assembly of human serum albumin (HSA) and l-alpha-dimyristoylphosphatidic acid (DMPA) microcapsules for controlled drug release

Chem Eur J

Biomimetic nanotechnology: inherent reversible stabilization of polypeptide microcapsules

Langmuir

Mesoporous silica particles as templates for preparing enzyme-loaded biocompatible microcapsules

Adv Mater

High-capacity functional protein encapsulation in nanoengineered polypeptide microcapsules

Chem Commun

Protein multilayer formation on colloids through a stepwise self-assembly technique

J Am Chem Soc

Nanoassembly of biodegradable microcapsules for DNA encasing

J Am Chem Soc

Self-rupturing and hollow microcapsules prepared from bio-polyelectrolyte-coated microgels

Adv Funct Mater

Enzyme-responsive release of encapsulated proteins from biodegradable hollow capsules

Biomacromolecules

Intracellularly degradable polyelectrolyte microcapsules

Adv Mater

Targeting and uptake of multilayered particles to colorectal cancer cells

Adv Mater

In vivo cellular uptake, degradation, and biocompatibility of polyelectrolyte microcapsules

Adv Funct Mater

Hollow polymer shells from biological templates: fabrication and potential applications

Chem Eur J

Liposomes: from physics to applications

Nanoparticle multilayers: surface modification of of photosensitive drug microparticles for increased stability and in vitro bioavailability

J Nanosci Nanotechnol

Encapsulation of proteins by layer-by-layer adsorption of polyelectrolytes onto protein aggregates: factors regulating the protein release

Biotechnol Bioeng

Encapsulation, permeability, and cellular uptake characteristics of hollow nanometer-sized conductive polymer capsules

J Phys Chem B

Controlled precipitation of dyes into hollow polyelectrolyte capsules based on colloids and biocolloids

Adv Mater

Smart micro- and nanocontainers for storage, transport, and release

Adv Mater

Original Article: Drug Delivery
pH-controlled drug loading and release from biodegradable microcapsules