Norfloxacin-Loaded Electrospun Scaffolds: Montmorillonite Nanocomposite vs. Free Drug

Abstract

Infections in nonhealing wounds remain one of the major challenges. Recently, nanomedicine approach seems a valid option to overcome the antibiotic resistance mechanisms. The aim of this study was the development of three types of polysaccharide-based scaffolds (chitosan-based (CH), chitosan/chondroitin sulfate-based (CH/CS), chitosan/hyaluronic acid-based (CH/HA)), as dermal substitutes, to be loaded with norfloxacin, intended for the treatment of infected wounds. The scaffolds have been loaded with norfloxacin as a free drug (N scaffolds) or in montmorillonite nanocomposite (H—hybrid-scaffolds). Chitosan/glycosaminoglycan (chondroitin sulfate or hyaluronic acid) scaffolds were prepared by means of electrospinning with a simple, one-step process. The scaffolds were characterized by 500 nm diameter fibers with homogeneous structures when norfloxacin was loaded as a free drug. On the contrary, the presence of nanocomposite caused a certain degree of surface roughness, with fibers having 1000 nm diameters. The presence of norfloxacin–montmorillonite nanocomposite (1%) caused higher deformability (90–120%) and lower elasticity (5–10 mN/cm2), decreasing the mechanical resistance of the systems. All the scaffolds were proven to be degraded via lysozyme (this should ensure scaffold resorption) and this sustained the drug release (from 50% to 100% in 3 days, depending on system composition), especially when the drug was loaded in the scaffolds as a nanocomposite. Moreover, the scaffolds were able to decrease the bioburden at least 100-fold, proving that drug loading in the scaffolds did not impair the antimicrobial activity of norfloxacin. Chondroitin sulfate and montmorillonite in the scaffolds are proven to possess a synergic performance, enhancing the fibroblast proliferation without impairing norfloxacin’s antimicrobial properties. The scaffold based on chondroitin sulfate, containing 1% norfloxacin in the nanocomposite, demonstrated adequate stiffness to sustain fibroblast proliferation and the capability to sustain antimicrobial properties to prevent/treat nonhealing wound infection during the healing process.

Halloysite- and Montmorillonite-Loaded Scaffolds as Enhancers of Chronic Wound Healing

“…MMT scaffolds were characterized by nanofiber portions with a regular, smooth surface spaced out in a broaden interwoven, resembling knots, and with a wider structure organisation. These conceivably could be related to montmorillonite [9,21]. The increase of MMT concentration, especially in the 5% MMT scaffold, caused an increase in the surface roughness of the fibers, while the fiber diameters were significantly lower than those of the blank scaffold, although this was not influenced from the clay concentration.…”

Nanotechnology-Based Medical Devices for the Treatment of Chronic Skin Lesions: From Research to the Clinic

“…These materials should be easily sterilizable and have acceptable levels of toxicity. The most common natural or naturally derived polymers used in scaffold development are collagen [ 46 , 47 , 48 ], gelatin [ 49 , 50 , 51 ], chitosan [ 52 , 53 , 54 , 55 ] and alginate [ 56 ].…”

“…These nanoparticles could either be loaded into the polymeric matrix or could be absorbed and coated onto a MD surface: this loading should confer antimicrobial properties to these constructs with an increasing effect over time. Figure 2 reports the images of nanofibrous scaffolds as dermal substitutes: (a) polymer-based matrix [ 55 ]; (b) polymer-based matrix embedded with silver nanoparticles [ 53 ]; (c) polymer-based matrix embedded with halloysite [ 54 ] and (d) with montmorillonite [ 54 ].…”

“…Native skin shows tensile strength values between 5.0 and 30.0 MPa, a Young’s modulus in the range of 4.6–20.0 MPa and elongation at break of about 35.0–115.0%; these values are wide since the skin mechanical properties vary depending on the body area, and the ageing (thinner and less flexible [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 ]). The ability of the scaffold to maintain its integrity during grafting is related to the tensile strength, while the performance of the scaffold upon grafting is related to elongation and the Young’s modulus.…”

“… Images of nanofibrous scaffolds as dermal substitutes: ( a ) polymer-based matrix; ( b ) polymer-based matrix embedded with silver nanoparticles; ( c ) polymer-based matrix embedded with halloysite and ( d ) with montmorillonite adapted from [ 53 , 54 , 55 ]. CC BY 4.0.…”