Development of Microspheres Based on Thiol-Modified Sodium Alginate for Intestinal-Targeted Drug Delivery

Abstract

Bioactive peptide drugs are mostly delivered by parenteral administration, which brings great pain and risks to patients. Oral administration is an acceptable alternative form. However, peptide drugs are extremely sensitive to the strong acidic environment in the stomach after oral administration. They would be degraded by pepsin and trypsin in the gastrointestinal tract. Herein, we present microspheres for intestinal-targeted peptides drug delivery through oral administration. Sodium alginate was reacted with l-cysteine to bring it into thiol groups. Then sodium alginate-l-cysteine conjugates were mixed with native sodium alginate and emulsified by an improved method. Ca2+ was used to fix the emulsion to get the microspheres. Bovine serum albumin was used as the simulating drug to assess the feasibility of microspheres as intestinal delivery carriers. The results showed that the microspheres exhibited spherical properties and narrow size distribution. The drug-loading capacity of microspheres was not compromised after thiol-modification. It is interesting that the microspheres can maintain structural integrity and hold drugs in the strong acidic environment in the stomach. Conversely, the microspheres presented sustained intestinal-targeted drugs release ability as expected. Moreover, thiol-modification further improved the adherence ability of microspheres on the inner walls of the small intestine, which is good for enhancing drug permeability. In sum, the microspheres based on thiol-modified sodium alginate have promising applications as intestinal-targeted macromolecular drug carriers.

Degradation-Dependent Controlled Delivery of Doxorubicin by Glyoxal Cross-Linked Magnetic and Porous Chitosan Microspheres

“…Multifunctional drug carriers are better particularly due to high loading capacity complemented with stimulus-responsive release kinetics such as temperature, pH, enzymes, photo conditions, magnetic/electric fields, etc . 4 , 5 , 10 , 22 − 25 The combined treatment methodologies like chemo-photodynamic therapy elicit synergistic effects at the tumor site, resulting in remarkable anticancer performance. 26 − 28 Recent applications proposed in theranostics include tumor microenvironment-responsive high-quality imaging in conjunction with drug release properties for oncotherapy.…”

“…The literature presents a wealth of information on the biomedical potential of chitosan, a biodegradable natural polymer, in the form of microspheres with regard to its excellent antibacterial property and tailored physicochemical and surface properties to enunciate regulated drug release in treating numerous diseases, including cancer. ,, In particular, specific targeting strategies of chitosan microspheres loaded with tumor-targeting drugs, e.g. , doxorubicin (DOX), 5-fluorouracil, etc ., significantly reduce the side effects of these drugs and enhance therapeutic efficiency. , In chitosan-based drug carriers, enhanced internalization by cells occurs by virtue of the electrostatic charge of amino groups in chitosan and facilitates a good endosomal escape ability .…”

“…Advanced drug delivery options for cancer therapeutics avoid premature release of drugs at the extracellular level by employing multifunctional carrier systems. Multifunctional drug carriers are better particularly due to high loading capacity complemented with stimulus-responsive release kinetics such as temperature, pH, enzymes, photo conditions, magnetic/electric fields, etc . ,,,− The combined treatment methodologies like chemo-photodynamic therapy elicit synergistic effects at the tumor site, resulting in remarkable anticancer performance. − Recent applications proposed in theranostics include tumor microenvironment-responsive high-quality imaging in conjunction with drug release properties for oncotherapy . Doping these nanocarriers with certain rare-earth metal ions imparts multimodal imaging potential, enabling image-guided treatment options.…”

“…Besides this, incorporation of noble-metal nanoparticles such as Pt expedites deep tumor penetration through interaction with adherent junctions between cells and subsequent tumor ablation . Among the several types of carriers, porous microspheres are especially attractive due to the capability of high loading efficiency offered by high surface area. − …”

Aminated Polysaccharide-Based Nanoassemblies as Stable Biocompatible Vehicles Enabling Crossing of Biological Barriers: An Effective Transdermal Delivery of Diclofenac Medicine

“…The important advantage of polysaccharides is their defined chemical structure that allows rational modifications and precise tuning of their properties . Polysaccharide-based delivery systems were hence successfully used in medicine, food, materials engineering, and water treatment. − …”