Preparation and modeling of three‐layered PCL/PLGA/PCL fibrous scaffolds for prolonged drug release

Abstract

The authors present the preparation procedure and a computational model of a three-layered fibrous scaffold for prolonged drug release. The scaffold, produced by emulsion/sequential electrospinning, consists of a poly(d,l-lactic-co-glycolic acid) (PLGA) fiber layer sandwiched between two poly(εcaprolactone) (PCL) layers. Experimental results of drug release rates from the scaffold are compared with the results of the recently introduced computational finite element (FE) models for diffusive drug release from nanofibers to the three-dimensional (3D) surrounding medium. Two different FE models are used: (1) a 3D discretized continuum and fibers represented by a simple radial one-dimensional (1D) finite elements, and (2) a 3D continuum discretized by composite smeared finite elements (CSFEs) containing the fiber smeared and surrounding domains. Both models include the effects of polymer degradation and hydrophobicity (as partitioning) of the drug at the fiber/surrounding interface. The CSFE model includes a volumetric fraction of fibers and diameter distribution, and is additionally enhanced by using correction function to improve the accuracy of the model. The computational results are validated on Rhodamine B (fluorescent drug l) and other hydrophilic drugs. Agreement with experimental results proves that numerical models can serve as efficient tools for drug release to the surrounding porous medium or biological tissue. It is demonstrated that the introduced three-layered scaffold delays the drug release process and can be used for the time-controlled release of drugs in postoperative therapy. A promising approach in modern medicine for drug delivery over a long time period and with a desirable rate is the use of nano-scaffolds 1-3 , and specifically electrospun-made scaffolds composed of drug loaded nanofiber mats 4-8. Fibers are preferably prepared using a biodegradable polymer 7 , and their main function is targeted and cites specific drug delivery in human body 1-5 , without any burst release 7 , and with improved physicochemical properties 6. This kind of drug delivery systems have provided many mechanisms that improve the therapeutic efficacy of both new and already existing drugs 7 , and may be now used for various paramedical and medical applications such as wound healing and cancer therapy 1-5. The advantages of using biodegradable polymers for drug delivery are: no need for the second surgery to remove the scaffold once the drug is released 9 , their enhanced biocompatibility, degradability, bioactivity and resorbability 8,10-12. Among the most commonly used biodegradable synthetic polymers, poly(lactic-co-glycolide (PLGA) copolymer is well recognized for drug delivery processes 13. PLGA is known for good biocompatibility and ability to achieve complete drug release 14 , which is the result of its degradation and erosion properties 15,16. Many

Further Evidence of Possible Therapeutic Uses of Sambucus nigra L. Extracts by the Assessment of the In Vitro and In Vivo Anti-Inflammatory Properties of Its PLGA and PCL-Based Nanoformulations

“…In contrast with empty NPs, the extract-loaded PLGA NPs revealed a decrease in size at the different temperatures tested over 12 months, while the extract-loaded PCL NPs presented an increase in size for RC and RT and a decrease in size at AC. The decrease of PLGA NPs' can be associated to the intrinsic nature of the polymer; PCL presents a higher hydrophobicity that can also contribute to this change [35]. Moreover, as it was verified by the TEM and AFM analysis, the PCL NPs presented an higher agglomeration tendency when compared to the PLGA NPs, which is also supported by the literature [36].…”

“…Moreover, the presence of H-bonding in the rutin-PLGA complex may have led to the retention of the rutin molecule within the PLGA matrix at physiological pH. Another important factor that can be associated with the rutin release is the fact that PCL presents higher hydrophilicity than PLGA [35]. The extract was successfully entrapped in both carriers.…”

Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro

“…Different polymers including poly( -caprolactone) (PCL), poly(lactic acid) (PLA), and poly(lactide-co-glycolide) (PLGA) are FDA-approved polymers that have been widely applied for biomedical and in particular tendon applications [1,2,[4][5][6][7][8][9][10][11][12][13][14]. Although PLA and PCL are two biocompatible polymers, they are characterized by high hydrophobic properties that decreased cell adhesion due to the lack of cell recognition sites on their surfaces [9,15,16]. This might lead to a long in vivo degradation rate, which restricts their target applications depending on the regeneration time of the damaged tissue [9,15,16].…”

Metronidazole- and Amoxicillin-Loaded PLGA and PCL Nanofibers as Potential Drug Delivery Systems for the Treatment of Periodontitis: In Vitro and In Vivo Evaluations

“…The more gradual and controlled release of drugs from the PCL nanofibers (196 h for the release of the metronidazole and 216 h for the release of the amoxicillin) compared to the PLGA nanofibers (168 h for the release of both drugs) may have been due to the higher hydrophobicity of PCL compared to PLGA [41]. This high hydrophobicity may have led to a decreased degree of swelling and consequently a slower release profile.…”