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  1. Inhaled nano-based therapeutics for inflammatory lung diseases: Recent advances and future prospects
    Gulati N, Chellappan DK, MacLoughlin R, Dua K, Dureja H
    Life Sci, 2021 Nov 15;285:119969.
    PMID: 34547339 DOI: 10.1016/j.lfs.2021.119969
    Inflammatory lung diseases related morbidity and mortality impose a significant financial burden. Inflammation is a hallmark of many diseases of the respiratory system which is directly or indirectly linked to adverse health conditions, air pollution, rapid lifestyle changes, and regular outbreaks of microbial infections. The unique anatomical and physiological features of the lungs make them an ideal target organ in the treatment of inflammatory respiratory disease and with the help of inhaled therapy lungs can be targeted directly. The principal objective of this review is to present the comprehensive role of inhaled nano-based therapeutics such as liposomes, niosomes, nanoparticles, nanoemulsion, nanosuspension, and exosomes in the treatment and management of inflammatory respiratory diseases. Inhaled nanomedicines provide targeted diagnosis and treatment, improved drug solubility and distribution, prevent first-pass hepatic metabolism, improved patient compliance, and reduced drug side effects. They overcome several biological barriers in the human body and provide immediate, and quick-onset of action. Future research should be focused on improving the therapeutic efficiency of inhaled nanocarriers and to carry out in-depth mechanistic studies to translate current scientific knowledge for the efficient management of inflammatory lung diseases with minimal or no toxicity.
  2. Central composite designed formulation, characterization and in vitro cytotoxic effect of erlotinib loaded chitosan nanoparticulate system
    Pandey P, Chellappan DK, Tambuwala MM, Bakshi HA, Dua K, Dureja H
    Int J Biol Macromol, 2019 Dec 01;141:596-610.
    PMID: 31494160 DOI: 10.1016/j.ijbiomac.2019.09.023
    The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer.
  3. Fulltext Emerging cases of mucormycosis under COVID-19 pandemic in India: Misuse of antibiotics
    Gupta G, S R, Singh Y, Thangavelu L, Singh SK, Dureja H, et al.
    Drug Dev Res, 2021 11;82(7):880-882.
    PMID: 34323298 DOI: 10.1002/ddr.21862
    COVID-19's second wave had a significant impact on India, on May 7, 2021, the largest daily recorded case count was a little more than 4 million, and it has since fallen. Although the number of new cases reported has dropped, during the third week of May 2021, India accounted for about 45% of new cases identified globally and around 34% of deaths. As India maintains its present level of stability, a new urgent threat has emerged in the form of coronavirus-associated mucormycosis. Mucormycosis, an acute and deadly fungal infection caused by Mucorales-related fungal species, is a fungal emergency with a particularly aggressive propensity for contiguous spread, associated with a poor prognosis if not properly and immediately identified, and treated. Mucormycosis, sometimes referred to as the "black fungus," has increased more rapidly in India during the second wave of COVID-19 than during the first wave, with at least 14,872 cases as of May 28, 2021. Uncontrolled diabetic mellitus (DM) and other immunosuppressive diseases such as neutropenia and corticosteroid treatment have traditionally been identified as risk factors for mucormycosis. Therefore, the use of glucocorticoids or high doses of glucocorticoids in mild COVID-19 cases (without hypoxemia) should be avoided. In addition, drugs that target the immune pathway, such as tocilizumab, are not recommended without clear benefits.
  4. Advances in nano-based drug delivery systems for the management of cytokine influx-mediated inflammation in lung diseases
    Gulati N, Chellappan DK, MacLoughlin R, Gupta G, Singh SK, Oliver BG, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec 11.
    PMID: 38078921 DOI: 10.1007/s00210-023-02882-y
    Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.
  5. Recent Trends and Applications of Nanostructure-based Drug Delivery in Alleviating Chronic Obstructive Pulmonary Disease (COPD)
    Lokesh, Gulati N, Saini A, Singh S, Gupta G, MacLoughlin R, et al.
    Curr Drug Deliv, 2024 Mar 05.
    PMID: 38445696 DOI: 10.2174/0115672018289883240226113353
    Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.
  6. Cationic cycloamylose based nucleic acid nanocarriers
    Prasher P, Sharma M, Agarwal V, Singh SK, Gupta G, Dureja H, et al.
    Chem Biol Interact, 2024 Apr 12;395:111000.
    PMID: 38614318 DOI: 10.1016/j.cbi.2024.111000
    Nucleic acid delivery by viral and non-viral methods has been a cornerstone for the contemporary gene therapy aimed at correcting the defective genes, replacing of the missing genes, or downregulating the expression of anomalous genes is highly desirable for the management of various diseases. Ostensibly, it becomes paramount for the delivery vectors to intersect the biological barriers for accessing their destined site within the cellular environment. However, the lipophilic nature of biological membranes and their potential to limit the entry of large sized, charged, hydrophilic molecules thus presenting a sizeable challenge for the cellular integration of negatively charged nucleic acids. Furthermore, the susceptibility of nucleic acids towards the degrading enzymes (nucleases) in the lysosomes present in cytoplasm is another matter of concern for their cellular and nuclear delivery. Hence, there is a pressing need for the identification and development of cationic delivery systems which encapsulate the cargo nucleic acids where the charge facilitates their cellular entry by evading the membrane barriers, and the encapsulation shields them from the enzymatic attack in cytoplasm. Cycloamylose bearing a closed loop conformation presents a robust candidature in this regard owing to its remarkable encapsulating tendency towards nucleic acids including siRNA, CpG DNA, and siRNA. The presence of numerous hydroxyl groups on the cycloamylose periphery provides sites for its chemical modification for the introduction of cationic groups, including spermine, (3-Chloro-2 hydroxypropyl) trimethylammonium chloride (Q188), and diethyl aminoethane (DEAE). The resulting cationic cycloamylose possesses a remarkable transfection efficiency and provides stability to cargo oligonucleotides against endonucleases, in addition to modulating the undesirable side effects such as unwanted immune stimulation. Cycloamylose is known to interact with the cell membranes where they release certain membrane components such as phospholipids and cholesterol thereby resulting in membrane destabilization and permeabilization. Furthermore, cycloamylose derivatives also serve as formulation excipients for improving the efficiency of other gene delivery systems. This review delves into the various vector and non-vector-based gene delivery systems, their advantages, and limitations, eventually leading to the identification of cycloamylose as an ideal candidate for nucleic acid delivery. The synthesis of cationic cycloamylose is briefly discussed in each section followed by its application for specific delivery/transfection of a particular nucleic acid.
  7. Emerging trends in nanomedicine for topical delivery in skin disorders: Current and translational approaches
    Pandey P, Satija S, Wadhwa R, Mehta M, Purohit D, Gupta G, et al.
    Dermatol Ther, 2020 05;33(3):e13292.
    PMID: 32126154 DOI: 10.1111/dth.13292
  8. Nanocarriers: more than tour de force for thymoquinone
    Rathore C, Rathbone MJ, Chellappan DK, Tambuwala MM, Pinto TJA, Dureja H, et al.
    Expert Opin Drug Deliv, 2020 04;17(4):479-494.
    PMID: 32077770 DOI: 10.1080/17425247.2020.1730808
    Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.
  9. Nanosuspensions - An Update on Recent Patents, Methods of Preparation, and Evaluation Parameters
    Khanuja HK, Awasthi R, Mehta M, Satija S, Aljabali AAA, Tambuwala MM, et al.
    Recent Pat Nanotechnol, 2021;15(4):351-366.
    PMID: 33357187 DOI: 10.2174/1872210514666201224103010
    BACKGROUND: Nanosuspensions are colloidal systems consisting of pure drug and stabilizers, without matrix or lyophilized into a solid matrix. Nanosuspensions improve the solubility of the drug both in the aqueous and organic phases. Nanosuspensions are also known as brick dust molecules, as they increase the dissolution of a system and improve absorption.

    METHODS: Extensive information related to nanosuspensions and its associated patents were collected using Pub Med and Google Scholar.

    RESULTS: Over the last decade nanosuspensions have attracted tremendous interest in pharmaceutical research. It provides unique features including, improved solubility, high drug loading capacity, and passive targeting. These particles are cost-effective, simple, and have lesser side effects with minimal dose requirements. However, the stability of nanosuspensions still warrants attention.

    CONCLUSION: Nanosuspensions play a vital role in handling the numerous drug entities with difficult physico-chemical characteristics such as solubility and can further aid with a range of routes that include nasal, transdermal, ocular, parenteral, pulmonary etc. This review highlights the relevance of nanosuspensions in achieving safe, effective and targeted drug delivery.

  10. Recent Trends in Rationally Designed Molecules as Kinase Inhibitors
    Prasher P, Sharma M, Chan Y, Singh SK, Anand K, Dureja H, et al.
    Curr Med Chem, 2023;30(13):1529-1567.
    PMID: 34766883 DOI: 10.2174/0929867328666211111161811
    Protein kinases modulate the structure and function of proteins by adding phosphate groups to threonine, tyrosine, and serine residues. The phosphorylation process mediated by the kinases regulates several physiological processes, while their overexpression results in the development of chronic diseases, including cancer. Targeting of receptor tyrosine kinase pathways results in the inhibition of angiogenesis and cell proliferation that validates kinases as a key target in the management of aggressive cancers. As such, the identification of protein kinase inhibitors revolutionized the contemporary anticancer therapy by inducing a paradigm shift in the management of disease pathogenesis. Contemporary drug design programs focus on a broad range of kinase targets for the development of novel pharmacophores to manage the overexpression of kinases and their pathophysiology in cancer pathogenesis. In this review, we present the emerging trends in the development of rationally designed molecular inhibitors of kinases over the last five years (2016-2021) and their incipient role in the development of impending anticancer pharmaceuticals.
  11. Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease
    Wadhwa R, Aggarwal T, Malyla V, Kumar N, Gupta G, Chellappan DK, et al.
    J Cell Physiol, 2019 08;234(10):16703-16723.
    PMID: 30912142 DOI: 10.1002/jcp.28482
    Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome-wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9).
  12. Fulltext Interferon therapy for preventing COPD exacerbations
    Mehta M, Paudel KR, Shukla SD, Shastri MD, Singh SK, Gulati M, et al.
    EXCLI J, 2020;19:1477-1480.
    PMID: 33312108 DOI: 10.17179/excli2020-2997
  13. Probing 3CL protease: Rationally designed chemical moieties for COVID-19
    Sharma M, Prasher P, Mehta M, Zacconi FC, Singh Y, Kapoor DN, et al.
    Drug Dev Res, 2020 Jul 30.
    PMID: 32729640 DOI: 10.1002/ddr.21724
  14. Fulltext Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies
    Anand K, Abdul NS, Ghazi T, Ramesh M, Gupta G, Tambuwala MM, et al.
    ACS Omega, 2021 Jan 12;6(1):265-277.
    PMID: 33458478 DOI: 10.1021/acsomega.0c04461
    In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH4. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
  15. Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms
    Chan Y, Ng SW, Xin Tan JZ, Gupta G, Tambuwala MM, Bakshi HA, et al.
    Chem Biol Interact, 2019 Nov 28;315:108911.
    PMID: 31786185 DOI: 10.1016/j.cbi.2019.108911
    Over the years, the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies, as they exhibit higher therapeutic efficacies and improved toxicological profiles. Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits, asperuloside, an iridoid glycoside, has been proven to provide promising effects as a therapeutic agent for several diseases. Although, this potent substance exists in several genera, it is primarily found in plants belonging to the genus Eucommia. Recent decades have seen a surge in the research on Asperuloside, making it one of the most studied natural products in the field of medicine and pharmacology. In this review, we have attempted to study the various reported mechanisms of asperuloside that form the basis of its wide spectrum of pharmacological activities.
  16. Nanocarriers for treatment of dermatological diseases: Principle, perspective and practices
    Ramanunny AK, Wadhwa S, Gulati M, Singh SK, Kapoor B, Dureja H, et al.
    Eur J Pharmacol, 2021 Jan 05;890:173691.
    PMID: 33129787 DOI: 10.1016/j.ejphar.2020.173691
    Skin diseases are the fourth leading non-fatal skin conditions that act as a burden and affect the world economy globally. This condition affects the quality of a patient's life and has a pronounced impact on both their physical and mental state. Treatment of these skin conditions with conventional approaches shows a lack of efficacy, long treatment duration, recurrence of conditions, systemic side effects, etc., due to improper drug delivery. However, these pitfalls can be overcome with the applications of nanomedicine-based approaches that provide efficient site-specific drug delivery at the target site. These nanomedicine-based strategies are evolved as potential treatment opportunities in the form of nanocarriers such as polymeric and lipidic nanocarriers, nanoemulsions along with emerging others viz. carbon nanotubes for dermatological treatment. The current review focuses on challenges faced by the existing conventional treatments along with the topical therapeutic perspective of nanocarriers in treating various skin diseases. A total of 213 articles have been reviewed and the application of different nanocarriers in treating various skin diseases has been explained in detail through case studies of previously published research works. The toxicity related aspects of nanocarriers are also discussed.
  17. Fulltext Effects of curcumin-loaded poly(lactic-co-glycolic acid) nanoparticles in MDA-MB231 human breast cancer cells
    Sharma A, Hawthorne S, Jha SK, Jha NK, Kumar D, Girgis S, et al.
    Nanomedicine (Lond), 2021 08;16(20):1763-1773.
    PMID: 34296625 DOI: 10.2217/nnm-2021-0066
    Aim: This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Methods: Curcumin-loaded PLGA NPs were developed using a modified solvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, in vitro experiments were conducted to study the biological activity of the curcumin-loaded NPs. Results: Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. Conclusion: The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.
  18. Rutin-loaded liquid crystalline nanoparticles attenuate oxidative stress in bronchial epithelial cells: a PCR validation
    Mehta M, Paudel KR, Shukla SD, Shastri MD, Satija S, Singh SK, et al.
    Future Med Chem, 2021 03;13(6):543-549.
    PMID: 33538615 DOI: 10.4155/fmc-2020-0297
    Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); γ-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.
  19. Oral Nanoemulsion of Fenofibrate: Formulation, Characterization, and In Vitro Drug Release Studies
    Gulati N, Kumar Chellappan D, M Tambuwala M, A A Aljabali A, Prasher P, Kumar Singh S, et al.
    Assay Drug Dev Technol, 2021 05 14;19(4):246-261.
    PMID: 33989048 DOI: 10.1089/adt.2021.012
    Nanoemulsions (NMs) are one of the most important colloidal dispersion systems that are primarily used to improve the solubility of poorly water soluble drugs. The main objectives of this study were, first, to prepare an NM loaded with fenofibrate using a high shear homogenization technique and, second, to study the effect of variable using a central composite design. Twenty batches of fenofibrate-loaded NM formulations were prepared. The formed NMs were subjected to droplet size analysis, zeta potential, entrapment efficiency, pH, dilution, polydispersity index, transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry, differential scanning calorimetry (DSC), and in vitro drug release study. Analysis of variance was used for entrapment efficiency data to study the fitness and significance of the design. The NM-7 batch formulation demonstrated maximum entrapment efficiency (81.82%) with lowest droplet size (72.28 nm), and was thus chosen as the optimized batch. TEM analysis revealed that the NM was well dispersed with droplet sizes <100 nm. Incorporation of the drug into the NM was confirmed with DSC studies. In addition, the batch NM-7 also showed the maximum in vitro drug release (87.6%) in a 0.05 M sodium lauryl sulfate solution. The release data revealed that the NM followed first-order kinetics. The outcomes of the study revealed the development of a stable oral NM containing fenofibrate using the high shear homogenization technique. This approach may aid in further enhancing the oral bioavailability of fenofibrate, which requires further in vivo studies.
  20. Opening eyes to therapeutic perspectives of bioactive polyphenols and their nanoformulations against diabetic neuropathy and related complications
    Khursheed R, Singh SK, Wadhwa S, Gulati M, Kapoor B, Awasthi A, et al.
    Expert Opin Drug Deliv, 2021 04;18(4):427-448.
    PMID: 33356647 DOI: 10.1080/17425247.2021.1846517
    Introduction: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.Area covered: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.Expert opinion: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards  development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.
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