Smart Carriers and Nanohealers: A Nanomedical Insight on Natural Polymers

Abstract

Biodegradable polymers are popularly being used in an increasing number of fields in the past few decades. The popularity and favorability of these materials are due to their remarkable properties, enabling a wide range of applications and market requirements to be met. Polymer biodegradable systems are a promising arena of research for targeted and site-specific controlled drug delivery, for developing artificial limbs, 3D porous scaffolds for cellular regeneration or tissue engineering and biosensing applications. Several natural polymers have been identified, blended, functionalized and applied for designing nanoscaffolds and drug carriers as a prerequisite for enumerable bionano technological applications. Apart from these, natural polymers have been well studied and are widely used in material science and industrial fields. The present review explains the prominent features of commonly used natural polymers (polysaccharides and proteins) in various nanomedical applications and reveals the current status of the polymer research in bionanotechnology and science sectors.

Keywords: biopolymers; drug delivery; nanoparticles; nanoscience; polymers; tissue engineering.

Figure 1

Structures of polysaccharides and proteins that are extensively explored for their uses in nanotechnology and regenerative medicine. Proteins show structural homology between human and bovine serum albumin structures (pink: human serum albumin and green: bovine serum albumin with RMSD score of 2.3). The figure also shows representative structure and electron microscope image of Laminin [8]. It also shows the human fibronectin fragment type III. Reproduced with permission from [8].

Figure 2

Extent of angiogenesis developed after three days of incubation with (A) PBS (negative control), (B) b-FGF (positive control), (C) CS-GP (glycerol phosphate)-HEC (hydroxyethyl propyl cellulose) hydrogel, (D) CS-GP-HEC/hMSCs (human derived mesenchymal stem cells)/BCP (biphasic calcium phosphate microparticles) hydrogel. Also known as with gel with hMSC. It clearly indicates formation of blood vessels and promotion of angiogenesis in hydrogel with hMSCs showing increased number of blood vessel formation compared to the control group (p < 0.05). and (E) CS GP-HEC/BCP hydrogel. Also known as gel without hMSCs. Reproduced with permission from [36].

Figure 3

(A,B) Effect of nano silicate on spread ability of hMSCs over a period of 7 days. It can be seen from the confocal images that hMSC-treated cells were able to show circular morphology, indicating that hMSC can be delivered for cartilage regeneration. (C) Shows that there is no change in the metabolic activity of seeded cells. Reproduced with permission from [63].

Figure 4

Wound healing using nanofiber patch healing with AG-PVA fibrous mat over a period of 20 days in comparison to control group. (A) control untreated group; (B) PVA nanofibers; (C) native AG-PVA nanofibers; (D) drug-loaded PVA fibers; (E) drug-loaded AG-PVA nanofibers; (F) marketed standard formulation. The study clearly indicates that drug-loaded AG-PVA nanofibers provided relatively better wound healing properties. Reproduced with permission from [90].

Figure 5

Cross section of porcine skin glued with HES-gelatin glue. It can be seen that by the end of 12th day the glue had completely disintegrated, and new connective tissue had developed. Reproduced with permission from [111].

Figure 6

(A) Circular morphology of the HepaRG and HepG2 cells in nanofibrillar cellulose (NFC) in comparison to the Puramatrix™ (PM) standard. Both showed similar cellular morphologies. (B) Shows the confocal images of the cells with structural staining of filamentous actin (red) and nuclei (blue). It can be seen that, in contrast to HepG2 cells, filamentous actin shows accumulation at the site of the apical membrane of HepaRG cells. This may be due to the in vivo-like polarity, which is known to be associated with canaliculus formation. The differentiation state of the HepaRG cells was also confirmed using secretion of albumin as a marker. (C) Shows the secretion of albumin by HepaRG. (D) Shows the secretion of albumin from HepG2 cells. Both the studies clearly indicate a release of albumin in cells treated with NFC that is comparable to standard commercial formulation. Reproduced with permission from [123].

Figure 7

Wound closure in diabetic rats for subjects treated with (A) GAG (glycosaminoglycan)-PA (Peptide amphiphiles)/K-PA (also known as positively charged heparin mimetic PAs), (B) PBS control, and (C) E-PA (negatively charged heparin mimetic PA)/K-PA. (D) shows the schematic diagram for the location of wound on the rats that were treated with GAG-PA/K-PA, PBS and E-PA/K-PA samples. (E) Shows the % wound closure studied for 14 days after the treatment. It can be seen that after 14 days of the treatment compared to control. It can be seen that GAG-PA/K-PA bio gel-treated group provided significant wound healing property on 14th day of treatment, compared to the E-PA/K-PA- or PBS-treated control groups (one way ANOVA test with * p < 0.05, ** p < 0.01, *** p < 0.001). Reproduced with permission from [150].

Figure 8

In vivo Evaluation of Gelatin/Hyaluronic Acid Nanofiber as Burn-wound Healing and Its Comparison with ChitoHeal Gel. (A) It can be seen that at the end of 14th day GE/HA nanofibrous scaffold is able to completely heal the wound in comparison to chitoheal gel control. (B) The H&E stained section of granulation tissue of control, chitoheal gel and GE/HA nanofibrous scaffold shows that irregular collagen bands that are evident in control are absent in GE/HA nanofibrous scaffold. Reproduced with permission from [240].

Figure 9

Hematoxylin and Enosin staining of wound after 24 and 48 h of treatment with silk nanofibers. (A,B) the control without silk dressing on the top of the wound, (C,D) samples of silk mat without EGF, (E,F) samples of silk mat consisting of EGF. It can be seen that silk mat with EGF shows complete closure of the wound after 48 h of incubation. Reproduced with permission from [261].

Figure 10

(a) Shows representative figure that depicts wound treatment on mice model (b). It shows that reduction of wound area for mice treated with test and control products over period of 9 days. It clearly shows closure with polyurethane keratin nanofibers (PU/K) with and without AgNPs in comparison to standard sponge dressing. It can be seen that both PU/K and PU/K/AgNs dressing shows wound healing on 9th day of treatment. The area of wound was reduced to 30% in case of PU/K- and PU/K/AgNP-treated rats. Reproduced with permission from [267].