Purna Sai Korrapati

Electrospun zein/eudragit nanofibers based dual drug delivery system for the simultaneous delivery of aceclofenac and pantoprazole

Electrospun composite zein/eudragit nanofibers were developed with an aim to deliver two different classes of drugs simultaneously that would restrict/compensate the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs). Co-administration of proton pump inhibitors is beneficial for patients consuming NSAIDs for treating chronic ailments like arthritis. In this study, aceclofenac/pantoprazole loaded zein/eudragit S 100 nanofibers were developed using a single nozzle electrospinning process. The morphological analysis revealed the uniform and smooth surface of the drug loaded nanofibers. The physico-thermal characterization of nanofibers depicted the molecular integration of the drugs with the polymers and also confirmed that the drugs were evenly distributed in the nanofibers in an amorphous state. In vitro release studies ensure the efficiency of the developed fibers in sustaining the release of both the drugs up to 8h. In vivo animal experiments further confirmed that the co-administration of pantoprazole along with aceclofenac reduced the gastro-intestinal toxicity induced by NSAIDs. The histological evaluation revealed the preserved mucosal architecture of rat gastric tissue treated with drug loaded composite nanofibers. Thus, dual drug delivery system comprising polymers with different release characteristics has been successfully developed and further, oral delivery of aceclofenac with reduced side effects was achieved.

A novel FRET ‘off–on’ fluorescent probe for the selective detection of Fe3+, Al3+ and Cr3+ ions: Its ultrafast energy transfer kinetics and application in live cell imaging

A rhodamine-naphthalimide dyad probe, 1, that selectively responds to the addition of trivalent metal ions (Fe(3+) or Al(3+) or Cr(3+)) via ultrafast Förster resonance energy transfer (FRET) from naphthalimide to rhodamine is designed and synthesized. 1 is highly selective to the trivalent metal ions and the presence of other monovalent or divalent metal ions do not affect its detection ability. The probe is highly sensitive and it can respond to the presence of trivalent metal ions even at sub-micromolar levels. 1 is stable over a broad range of pH, non-toxic under experimental conditions and suitable to the fluorescence bio-imaging of live cells exposed to trivalent metal ions. The trivalent metal ion induced ultrafast energy transfer kinetics of 1 is explored using time resolved fluorescence experiments.

Fabrication of highly aligned fibrous scaffolds for tissue regeneration by centrifugal spinning technology.

Centrifugal spinning (C-Spin) is an emerging technology which uses centrifugal force to produce ultrafine fibers. Being a voltage free technique it can overcome the limitations of electrospinning. Owing to the unique characteristic features such as high surface area to volume ratio, porosity, mechanical strength and fiber alignment, centrifugal spun (C-spun) fibrous mat has a wide range of scope in various biomedical applications. Higher degree of fiber alignment can be effortlessly achieved by the C-Spin process. In order to prove the versatility of C-Spin system with respect to fiber alignment, Polycaprolactone (PCL) and gelatin were spun taking them as model polymers. The morphological analysis revealed that highly aligned ultrafine fibers with smooth surface are achieved by C-Spinning. Hydrophilicity, porosity and mechanical property results confirm that the C-spun mat is more suitable for tissue engineering applications. In vitro and in vivo experiments proved that the scaffolds are biocompatible and can be efficiently used as a wound dressing material.

Recent advancements in nanotechnological strategies in selection, design and delivery of biomolecules for skin regeneration

Skin is a very complex organ and hence designing a bioengineered skin model replicating the essential physiological characteristics for replacing the diseased or damaged parts has been a challenging goal for many. Newer technologies for satisfying most of the criteria are being attempted with the copious efforts of biologists, engineers, physiologists, using multitude of features in combination. Amongst them nanotechnology based biomaterials have gained prominence owing to the enhanced pharmacokinetics, bio-distribution profile, extended half-life and reduced side effects. Designing a matrix that can be assimilated into the body during the regeneration and delivering the essential pharmacological agents in a temporal and spatially specific manner is a tremendous goal. This review essentially deals with the various approaches for designing a multidisciplinary translational smart matrix for addressing the various skin related ailments.

Plumbagin caged silver nanoparticle stabilized collagen scaffold for wound dressing

The present work describes the development of a novel wound dressing material based on nano-biotechnological intervention by caging plumbagin on silver nanoparticle (PCSN) as a multi-site cross-linking agent of collagen scaffolds with potent anti-microbial and wound healing activity. Cross-linking of collagen with PCSN enhanced the physical, thermal, and mechanical properties along with the kinetics of micro structural fibril assembly of the collagen molecule. FTIR and CD analysis revealed that cross-linking of collagen using PCSN did not induce any structural changes in the collagen molecule. Further, cross-linking of collagen with PCSN resulted in uniform alignment of collagen fibrils to form orderly aligned porous structured scaffolds with potent anti-bacterial activity that in turn enhanced its ability to promote cell proliferation and wound healing. The cross-linking ability, and biochemical and therapeutic properties of plumbagin caged silver nanoparticles were attributed to the cumulative effect of plumbagin and silver nanoparticles because individual molecules had minimal effect on these parameters.

Fabrication of chitosan-polycaprolactone composite nanofibrous scaffold for simultaneous delivery of ferulic acid and resveratrol

Wound healing is a complex cellular process involving various mechanisms making it intricate for designing a scaffold for therapeutic use. This study deals with the designing and development of coaxial electrospun Chitosan-Polycaprolactone nanofiber wound dressings for efficient simultaneous drug delivery. Ferulic acid and resveratrol were chosen for incorporation into core-shell nanofibers for their efficacy in anti-inflammatory and pro-angiogenic activities respectively. Structural and physico-chemical characterization of the scaffold confirmed the encapsulation of both the molecules. The in vitro release studies showed sustained release of both resveratrol and ferulic acid up to 48% and 55% respectively till 120h. Functional characterization of the nanofibrous wound dressing exhibited good in vitro and in vivo biocompatibility. The scaffold treated rats exhibited complete healing in 15days in comparison to the controls that healed in 20days. The study therefore, opens up venues for designing sequential and sustained drug delivery systems in wound therapeutics.

Design and development of papain–urea loaded PVA nanofibers for wound debridement

Devitalized tissues present in a wound bed serve as a reservoir for bacterial growth and contain elevated levels of inflammatory mediators that promote chronic inflammation and impair cellular migration necessary for wound repair. Effective wound cleansing and debridement are essential for granulation and re-epithelization. Among various debridement methods, enzymatic debridement is a highly selective method that uses naturally occurring proteolytic enzymes. Papain combined with urea has been widely used to remove necrotic/devitalized tissues. Our approach is to encapsulate papain and urea in PVA nanofibers to bring out sustained release to enable breakdown of fibrinous material in necrotic tissue and enhance wound healing. Physico-chemical characterization of nanofibers depicted the enzyme interaction with the polymer and also confirmed that the enzyme was evenly distributed in the nanofibers in an amorphous state. Fluorescence spectroscopy confirmed that the structural integrity of the enzyme was maintained after encapsulation. The results of antibacterial activity along with cell compatibility assays confirm the structural and functional integrity of the enzyme preparation along with the biocompatibility of the electrospun nanofiber and thereby provide more suitability as a dressing for wound debridement.

Dinuclear phenoxo-bridged "end-off" complexes containing a piperazine that shows chemical nuclease and cytotoxic activities

Three dinuclear cobalt(II), nickel(II), and copper(II) complexes (1–3) of a phenol-based ‘end-off’ compartmental ligand, 2,6-bis[1-(N-ethyl)piperazineiminomethyl]-4-methylphenol (HL), have been synthesized and characterized by spectral analysis. The molecular structure of one of these complexes, 2,6-bis[1-(N-ethyl)piperazineiminomethyl]-4-methylphenolato-diaqua-μ-hydroxo-μ-nitrato-dicobalt(II) nitrate, [Co2(H2L)(μ-OH)(μ-NO3)(H2O)2](NO3)3] (1), was determined by single crystal X-ray crystallography. The complex exhibits a distorted octahedral geometry around cobalt with a Co–Co distance of 2.9882(8) Å. Electrochemical studies of 1–3 reveal that the redox processes are due to ligand reactions. The EPR spectrum of 3 showed a broad signal at g = 2.11 indicating magnetic interaction between the two copper ions. The μeff values for 1 and 3 are 4.94 and 1.93 BM, respectively, which indicate a spin–spin interaction between the metal ions. Complex 3 caused a cleavage of circular plasmid pBR322 DNA into nicked circular and linear forms in the presence of a co-reactant. Human epidermoid carcinoma cells, A431, were employed for in vitro cytotoxicity studies of the synthesized complexes. The IC50 value of 3 is lower than that of the other two complexes. The copper complex (3) exhibited better chemical nuclease and cytotoxic activity than the other two complexes. Graphical Abstract

Role of Dermatopontin in re-epithelialization: Implications on keratinocyte migration and proliferation

Re-epithelialization is a key event in wound healing and any impairment in that process is associated with various pathological conditions. Epidermal keratinocyte migration and proliferation during re-epithelialization is largely regulated by the cytokines and growth factors from the provisional matrix and dermis. Extracellular matrix consists of numerous growth factors which mediate cell migration via cell membrane receptors. Dermatopontin (DPT), a non-collagenous matrix protein highly expressed in dermis is known for its striking ability to promote cell adhesion. DPT also enhances the biological activity of transforming growth factor beta 1 which plays a central role in the process of wound healing. This study was designed to envisage the role of DPT in keratinocyte migration and proliferation along with its mRNA and protein expression pattern in epidermis. The results showed that DPT promotes keratinocyte migration in a dose dependant fashion but fail to induce proliferation. Further, PCR and immunodetection studies revealed that the mRNA and protein expression of DPT is considerably negligible in the epidermis in contrast to the dermis. To conclude, DPT has a profound role in wound healing specifically during re-epithelialization by promoting keratinocyte migration via paracrine action from the underlying dermis.

Fabrication of a triiodothyronine incorporated nanofibrous biomaterial: its implications on wound healing

With rising incidents of non-healing chronic wounds, functional restoration of the organs after a major wound insult is an essential requisite. The delivery of endogenous molecules through nanomaterials for supporting healing of such wounds has gained impetus in the past decade. Triiodothyronine (T3) is a hormone that exerts its activity at various target organs and is reported to play a critical role in repair and regeneration of tissues after injury. The encapsulation of T3 in nanofibers and its sustained release to enable wound healing has been attempted for the first time in this work. The physico-chemical characterization confirmed the encapsulation and uniform distribution of the hormone in the nanofiber. Functional characterization of the composite nanofibers revealed the significant positive influence of the T3-entrapped nanofibers on the proliferation and migration of skin cells. Consistent with the in vitro results, application of the composite nanofibers on full thickness excisional wounds in rat model (in vivo) confirmed the potential of the hormone in accelerating the rate of wound closure. Thus this work reveals the effect of prolonged sustained delivery of T3 from nanofibers which might promote the healing of chronic wounds.