Investigating Novel Syntheses of a Series of Unique Hybrid PLGA-Chitosan Polymers for Potential Therapeutic Delivery Applications.

Jason Thomas Duskey,Maria Angela Vandelli,Giovanni Tosi,Federica Da Ros,Cecilia Baraldi,Maria Cristina Gamberini,Ilaria Ottonelli,Flavio Forni,Barbara Ruozi

doi:10.3390/polym12040823

Jason Thomas Duskey, Maria Angela Vandelli + Show 7 more

Open Access

https://doi.org/10.3390/polym12040823

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Abstract

Discovering new materials to aid in the therapeutic delivery of drugs is in high demand. PLGA, a FDA approved polymer, is well known in the literature to form films or nanoparticles that can load, protect, and deliver drug molecules; however, its incompatibility with certain drugs (due to hydrophilicity or charge repulsion interactions) limits its use. Combining PLGA or other polymers such as polycaprolactone with other safe and positively-charged molecules, such as chitosan, has been sought after to make hybrid systems that are more flexible in terms of loading ability, but often the reactions for polymer coupling use harsh conditions, films, unpurified products, or create a single unoptimized product. In this work, we aimed to investigate possible innovative improvements regarding two synthetic procedures. Two methods were attempted and analytically compared using nuclear magnetic resonance (NMR), fourier-transform infrared spectroscopy (FT-IR), and dynamic scanning calorimetry (DSC) to furnish pure, homogenous, and tunable PLGA-chitosan hybrid polymers. These were fully characterized by analytical methods. A series of hybrids was produced that could be used to increase the suitability of PLGA with previously non-compatible drug molecules.

Highlights

The discovery of effective therapeutic drugs is becoming increasingly difficult as seen by the drastic decline of new therapeutics accepted for public use each year
The most direct method of conjugating poly(lactic-co-glycolic acid) (PLGA) and chitosan is an amid bond formation between the amine on chitosan and the carboxylic acid of PLGA (Scheme 1)
Previous attempts reacted chitosan in solution with a PLGA film to create a positively-charged surface aiming to create nanofibers without the need for purification [24]

Summary

Introduction

The discovery of effective therapeutic drugs is becoming increasingly difficult as seen by the drastic decline of new therapeutics accepted for public use each year This is seen even with advances in structure activity relationship (SAR) studies [1], computer simulations of target structures (specific binding sequences and shape elucidation) [2], and high throughput screening methodology [3]. Polymers 2020, 12, 823 systems to include targeting [4,5,6], triggerable activation (heat, light, reactive oxygen species (ROS), pH) [7,8,9], and varied uptake mechanisms to deliver pharmaceutics against numerous diseases [10,11,12] In this respect, poly(lactic-co-glycolic acid) (PLGA) is of high interest due to the fact that it is: (1) FDA approved; (2) chemico-physically tunable to match biodistribution or loading needs;. All of these aspects have been widely exploited in production of PLGA nanoparticles (NPs) for the possible cure of a plethora of diseases [13,14,15,16,17,18]

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