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Silver nanoparticle functionalized CS-g-(CA-MA-PZA) carrier for sustainable anti-tuberculosis drug delivery

Amarnath Praphakar R, Jeyaraj M, Ahmed M, Suresh Kumar S, Rajan M

Int J Biol Macromol, 2018 Oct 15;118(Pt B):1627-1638.
PMID: 29981824 DOI: 10.1016/j.ijbiomac.2018.07.008

Recently, drug functionalized biodegradable polymers have been appreciated to be imperative to fabricate multi-drug delivery nanosystems for sustainable drug release. In this work, amphiphilic chitosan-grafted-(cetyl alcohol-maleic anhydride-pyrazinamide) (CS-g-(CA-MA-PZA)) was synthesized by multi-step reactions. The incorporation of rifampicin (RF) and entrapment of silver nanoparticles (Ag NPs) on CS-g-(CA-MA-PZA) polymer was carried out by dialysis technique. From the FT-IR experiment, the polymer modification, incorporation of drugs and the entrapment of Ag NPs on micelles were confirmed. The surface morphology of Ag NPs, polymeric system and drug loaded micelles was described by SEM, TEM and AFM techniques. In addition, the controlled release behaviour of CS-g-(CA-MA-PZA) micelles was studied by UV-Vis spectroscopy. In vitro cell viability, cell apoptosis and cellular uptake experiments shows that multi-drug delivery system could enhance the biocompatibility and higher the cytotoxicity effect on the cells. Since the prepared amphiphilic polymeric micelles exhibit spotty features and the system is a promising strategy for a novel candidate for immediate therapeutically effects for alveolar macrophages.
Current advances in the development of meniscus tissue engineering: narrative review

Tong JB, Sanjiv R, Elderdery A, Wu X, Rajesh R, Suresh Kumar S, et al.

Med J Malaysia, 2023 Jul;78(4):534-540.
PMID: 37518929

INTRODUCTION: The meniscus plays an important role in maintaining homeostasis to facilitate the normal function of the knee joint. It is one of the most commonly injured areas of the knee joint. Meniscal-related injuries can lead to significantly decreased athletic ability, and their incidence has increased yearly. It has been found that most meniscal injuries are irreparable, and meniscectomy can increase the predisposition to knee osteoarthritis. Tissue engineering technology on meniscus repairing and transplantation has received widespread attention recently. This review aimed to analyse the scientific literature regarding the potential applications of tissue engineering on meniscus repairing and transplantation procedures.
METHOD AND MATERIALS: The electronic search was carried out using PubMed/MEDLINEⓇdatabases with the keywords "tissue engineering AND meniscus" spanning the period of publications from Jan 1980 until Dec 2022.
RESULTS: The literature search identified 405 references in PubMed/MEDLINE, and 179 were selected following the eligibility requirements. The research analysis showed that the existing meniscal tissue engineering studies used a wide variety of seed cells, cytokines, bioactive materials and 3D structures. Each showed distinct advantages and disadvantages in terms of biocompatibility, degradability, mechanical strength, porosity, and etc. It was noted that 3D printing technology is promising for tissue engineering meniscus research. In addition, the optimal use of compression and hydrostatic pressure to markedly improve the functional properties of tissue-engineering meniscal can serve as an useful strategy.
CONCLUSION: This review analysed the different approaches employed for meniscus tissue engineering and regeneration. Meniscal tissue engineering still faces several major challenges in terms of seed cells, choice of materials and 3D printing strategies, which should be effectively overcome to harness the full potential of this technology.
Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery

Yuan X, Amarnath Praphakar R, Munusamy MA, Alarfaj AA, Suresh Kumar S, Rajan M

Carbohydr Polym, 2019 Feb 15;206:1-10.
PMID: 30553301 DOI: 10.1016/j.carbpol.2018.10.098

Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.
Fulltext Suppression of Proinflammatory Cytokines and Mediators in LPS-Induced RAW 264.7 Macrophages by Stem Extract of Alternanthera sessilis via the Inhibition of the NF-κB Pathway

Muniandy K, Gothai S, Badran KMH, Suresh Kumar S, Esa NM, Arulselvan P

J Immunol Res, 2018;2018:3430684.
PMID: 30155492 DOI: 10.1155/2018/3430684

Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1β, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.
Fulltext Computational drug screening against the SARS-CoV-2 Saudi Arabia isolates through a multiple-sequence alignment approach

Mok PL, Koh AE, Farhana A, Alsrhani A, Alam MK, Suresh Kumar S

Saudi J Biol Sci, 2021 Apr;28(4):2502-2509.
PMID: 33551661 DOI: 10.1016/j.sjbs.2021.01.051

COVID-19 is a rapidly emerging infectious disease caused by the SARS-CoV-2 virus currently spreading throughout the world. To date, there are no specific drugs formulated for it, and researchers around the globe are racing against the clock to investigate potential drug candidates. The repurposing of existing drugs in the market represents an effective and economical strategy commonly utilized in such investigations. In this study, we used a multiple-sequence alignment approach for preliminary screening of commercially-available drugs on SARS-CoV sequences from the Kingdom of Saudi Arabia (KSA) isolates. The viral genomic sequences from KSA isolates were obtained from GISAID, an open access repository housing a wide variety of epidemic and pandemic virus data. A phylogenetic analysis of the present 164 sequences from the KSA provinces was carried out using the MEGA X software, which displayed high similarity (around 98%). The sequence was then analyzed using the VIGOR4 genome annotator to construct its genomic structure. Screening of existing drugs was carried out by mining data based on viral gene expressions from the ZINC database. A total of 73 hits were generated. The viral target orthologs were mapped to the SARS-CoV-2 KSA isolate sequence by multiple sequence alignment using CLUSTAL OMEGA, and a list of 29 orthologs with purchasable drug information was generated. The results showed that the SARS CoV replicase polyprotein 1a had the highest sequence similarity at 79.91%. Through ZINC data mining, tanshinones were found to have high binding affinities to this target. These compounds could be ideal candidates for SARS-CoV-2. Other matches ranged between 27 and 52%. The results of this study would serve as a significant endeavor towards drug discovery that would increase our chances of finding an effective treatment or prevention against COVID19.
Production, characterization and application of nanocarriers made of polysaccharides, proteins, bio-polyesters and other biopolymers: A review

Samrot AV, Sean TC, Kudaiyappan T, Bisyarah U, Mirarmandi A, Faradjeva E, et al.

Int J Biol Macromol, 2020 Dec 15;165(Pt B):3088-3105.
PMID: 33098896 DOI: 10.1016/j.ijbiomac.2020.10.104

Chitosan, collagen, gelatin, polylactic acid and polyhydroxyalkanoates are notable examples of biopolymers, which are essentially bio-derived polymers produced by living cells. With the right techniques, these biological macromolecules can be exploited for nanotechnological advents, including for the fabrication of nanocarriers. In the world of nanotechnology, it is highly essential (and optimal) for nanocarriers to be biocompatible, biodegradable and non-toxic for safe in vivo applications, including for drug delivery, cancer immunotherapy, tissue engineering, gene delivery, photodynamic therapy and many more. The recent advancements in understanding nanotechnology and the physicochemical properties of biopolymers allows us to modify biological macromolecules and use them in a multitude of fields, most notably for clinical and therapeutic applications. By utilizing chitosan, collagen, gelatin, polylactic acid, polyhydroxyalkanoates and various other biopolymers as synthesis ingredients, the 'optimal' properties of a nanocarrier can easily be attained. With emphasis on the aforementioned biological macromolecules, this review presents the various biopolymers utilized for nanocarrier synthesis along with their specific synthetization methods. We further discussed on the characterization techniques and related applications for the synthesized nanocarriers.
Purification of human adipose-derived stem cells from fat tissues using PLGA/silk screen hybrid membranes

Chen DC, Chen LY, Ling QD, Wu MH, Wang CT, Suresh Kumar S, et al.

Biomaterials, 2014 May;35(14):4278-87.
PMID: 24565521 DOI: 10.1016/j.biomaterials.2014.02.004

The purification of human adipose-derived stem cells (hADSCs) from human adipose tissue cells (stromal vascular fraction) was investigated using membrane filtration through poly(lactide-co-glycolic acid)/silk screen hybrid membranes. Membrane filtration methods are attractive in regenerative medicine because they reduce the time required to purify hADSCs (i.e., less than 30 min) compared with conventional culture methods, which require 5-12 days. hADSCs expressing the mesenchymal stem cell markers CD44, CD73, and CD90 were concentrated in the permeation solution from the hybrid membranes. Expression of the surface markers CD44, CD73, and CD99 on the cells in the permeation solution from the hybrid membranes, which were obtained using 18 mL of feed solution containing 50 × 10⁴ cells, was statistically significantly higher than that of the primary adipose tissue cells, indicating that the hADSCs can be purified in the permeation solution by the membrane filtration method. Cells expressing the stem cell-associated marker CD34 could be successfully isolated in the permeation solution, whereas CD34⁺ cells could not be purified by the conventional culture method. The hADSCs in the permeation solution demonstrated a superior capacity for osteogenic differentiation based on their alkali phosphatase activity, their osterix gene expression, and the results of mineralization analysis by Alizarin Red S and von Kossa staining compared with the cells from the suspension of human adipose tissue. These results suggest that the hADSCs capable of osteogenic differentiation preferentially permeate through the hybrid membranes.