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Theranostic application of nanoemulsions in chemotherapy

Gorain B, Choudhury H, Nair AB, Dubey SK, Kesharwani P

Drug Discov Today, 2020 07;25(7):1174-1188.
PMID: 32344042 DOI: 10.1016/j.drudis.2020.04.013

Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.
Emerging role of nanocarriers based topical delivery of anti-fungal agents in combating growing fungal infections

Waghule T, Sankar S, Rapalli VK, Gorantla S, Dubey SK, Chellappan DK, et al.

Dermatol Ther, 2020 11;33(6):e13905.
PMID: 32588940 DOI: 10.1111/dth.13905

The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.
Recent advances in nanoparticles mediated photothermal therapy induced tumor regression

Kumar AVP, Dubey SK, Tiwari S, Puri A, Hejmady S, Gorain B, et al.

Int J Pharm, 2021 Sep 05;606:120848.
PMID: 34216762 DOI: 10.1016/j.ijpharm.2021.120848

Photothermal therapy (PTT) is a minimally invasive procedure for treating cancer. The two significant prerequisites of PTT are the photothermal therapeutic agent (PTA) and near-infrared radiation (NIR). The PTA absorbs NIR, causing hyperthermia in the malignant cells. This increased temperature at the tumor microenvironment finally results in tumor cell damage. Nanoparticles play a crucial role in PTT, aiding in the passive and active targeting of the PTA to the tumor microenvironment. Through enhanced permeation and retention effect and surface-engineering, specific targeting could be achieved. This novel delivery tool provides the advantages of changing the shape, size, and surface attributes of the carriers containing PTAs, which might facilitate tumor regression significantly. Further, inclusion of surface engineering of nanoparticles is facilitated through ligating ligands specific to overexpressed receptors on the cancer cell surface. Thus, transforming nanoparticles grants the ability to combine different treatment strategies with PTT to enhance cancer treatment. This review emphasizes properties of PTAs, conjugated biomolecules of PTAs, and the combinatorial techniques for a better therapeutic effect of PTT using the nanoparticle platform.
Recent advances of gold nanoparticles as biomaterial in dentistry

Bapat RA, Chaubal TV, Dharmadhikari S, Abdulla AM, Bapat P, Alexander A, et al.

Int J Pharm, 2020 Aug 30;586:119596.
PMID: 32622805 DOI: 10.1016/j.ijpharm.2020.119596

Major goal of dental treatment is to eradicate the existing diseases of the oral cavity and implement preventive measures to control the spread of the diseases. Various interventions are being used to cure the dental diseases. Due to the nanostructures, high surface volume and biocompatibility, Gold nanoparticles (GNPs) have been experimented in the treatment of gum diseases, dental caries, tissue engineering, dental implantology and diagnosis of cancers. GNPs possess antifungal and antibacterial activity, hence are incorporated in various biomaterials to potentiate the effect. They also enhance the mechanical properties of materials leading to improved outcomes. They are available in different sizes and concentrations to exhibits its beneficial outcomes. These properties of GNPs make these materials as choice of fillers in biomaterials. This review aims to discuss the effect of incorporation of GNPs in several biomaterials used for dental and medical applications.
Oral peptide delivery: challenges and the way ahead

Dubey SK, Parab S, Dabholkar N, Agrawal M, Singhvi G, Alexander A, et al.

Drug Discov Today, 2021 04;26(4):931-950.
PMID: 33444788 DOI: 10.1016/j.drudis.2021.01.001

Peptides and proteins have emerged as potential therapeutic agents and, in the search for the best treatment regimen, the oral route has been extensively evaluated because of its non-invasive and safe nature. The physicochemical properties of peptides and proteins along with the hurdles in the gastrointestinal tract (GIT), such as degrading enzymes and permeation barriers, are challenges to their delivery. To address these challenges, several conventional and novel approaches, such as nanocarriers, site-specific and stimuli specific delivery, are being used. In this review, we discuss the challenges to the oral delivery of peptides and the approaches used to tackle these challenges.
Recent advances in targeted nanomedicine as promising antitumor therapeutics

Hejmady S, Pradhan R, Alexander A, Agrawal M, Singhvi G, Gorain B, et al.

Drug Discov Today, 2020 12;25(12):2227-2244.
PMID: 33011342 DOI: 10.1016/j.drudis.2020.09.031

A tumor serves as a major avenue in drug development owing to its complexity. Conventional therapies against tumors possess limitations such as suboptimal therapeutic efficacy and extreme side effects. These display poor pharmacokinetics and lack specific targeting, with non-specific distribution resulting in systemic toxicity. Therefore, nanocarriers targeted against cancers are increasingly being explored. Nanomedicine aids in maintaining a balance between efficacy and toxicity by specifically accumulating in tumors. Nanotherapeutics possess advantages such as increased solubility of chemotherapeutics, encapsulation of multiple drugs and improved biodistribution, and can ensure tumor-directed drug delivery and release via the approaches of passive targeting and active targeting. This review aims to offer a general overview of the current advances in tumor-targeting nanocarriers for clinical and diagnostic use.
Emerging landscape in psoriasis management: From topical application to targeting biomolecules

Rapalli VK, Singhvi G, Dubey SK, Gupta G, Chellappan DK, Dua K

Biomed Pharmacother, 2018 Oct;106:707-713.
PMID: 29990862 DOI: 10.1016/j.biopha.2018.06.136

Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.
Bacterial biofilms associated skin disorders: Pathogenesis, advanced pharmacotherapy and nanotechnology-based drug delivery systems as a treatment approach

Vyas T, Rapalli VK, Chellappan DK, Dua K, Dubey SK, Singhvi G

Life Sci, 2021 Dec 15;287:120148.
PMID: 34785190 DOI: 10.1016/j.lfs.2021.120148

BACKGROUND: Biofilms are microcolonies of microbes that form communities with a variety of microbes, exhibit the same gene composition but differ in gene expression. Biofilm-associated infections have been in existence for a long, however, biofilm-associated skin disorders have not been investigated much.
OBJECTIVES: Biofilms, which are made mostly of the matrix can be thought of as communities of microbes that are more virulent and more difficult to eradicate as compared to their planktonic counterparts. Currently, several formulations are available in the market which have the potential to treat biofilm-assisted skin disorders. However, the existing pharmacotherapies are not competent enough to cure them effectively and entirely, in several cases.
KEY FINDINGS: Especially with the rising resistance towards antibiotics, it has become particularly challenging to ameliorate these disorders completely. The new approaches are being used to combat biofilm-associated skin disorders, some of them being photodynamic therapy, nanotherapies, and the use of novel drug delivery systems. The focus of attention, however, is nanotherapy. Micelles, solid lipid nanoparticles, quatsomes, and many others are being considered to find a better solution for the biofilm-associated skin disorders.
SIGNIFICANCE: This review is an attempt to give a perspective on these new approaches for treating bacterial biofilms associated with skin disorders.
A Review of Phytochemical and Pharmacological Properties of Alpinia malaccensis (Burm. F.) Roscoe. (Zingiberaceae)

Mahawer S, Kumar R, Prakash O, Singh S, Singh Rawat D, Dubey SK, et al.

Curr Top Med Chem, 2023;23(20):1964-1972.
PMID: 37218200 DOI: 10.2174/1568026623666230522104104

Alpinia malaccensis, commonly known as "Malacca ginger" and "Rankihiriya," is an important medicinal plant of Zingiberaceae. It is native to Indonesia and Malaysia and widely distributed in countries including Northeast India, China, Peninsular Malaysia and Java. Due to vide pharmacological values, it is necessary to recognize this species for its significance of pharmacological importance. This article provides the botanical characteristics, chemical compounds of vegetation, ethnopharmacological values, therapeutic properties, along with the potential pesticidal properties of this important medicinal plant. The information in this article was gathered by searching the online journals in the databases such as PubMed, Scopus, Web of Science etc. The terms such as Alpinia malaccensis, Malacca ginger, Rankihiriya, pharmacology, chemical composition, ethnopharmacology, etc., were used in different combinations. A detailed study of the available resources for A. malaccensis confirmed its native and distribution, traditional values, chemical properties, and medicinal values. Its essential oils and extracts are the reservoir of a wide range of important chemical constituents. Traditionally, it is being used to treat nausea, vomiting and wounds along with as a seasoning agent in meat processing and as perfume. Apart from traditional values, it has been reported for several pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory etc. We believe that this review will help to provide the collective information of A. malaccensis to further explore it in the prevention and treatment of various diseases and help to the systematic study of this plant to utilize its potential in various areas of human welfare.
Recent advancement on albumin nanoparticles in treating lung carcinoma

Sristi, Fatima M, Sheikh A, Almalki WH, Talegaonkar S, Dubey SK, et al.

J Drug Target, 2023 Jun;31(5):486-499.
PMID: 37125741 DOI: 10.1080/1061186X.2023.2205609

With the advancement of nanotechnology, many different forms of nanoparticles (NPs) are created, which specifically enhance anticancer drug delivery to tumour cells. Albumin bio-macromolecule is a flexible protein carrier for the delivery of drugs that is biodegradable, biocompatible, and non-toxic. As a result, it presents itself as an ideal material for developing nanoparticles for anticancer drug delivery. Toxicological investigations demonstrated that this novel drug delivery technique is safe for use in the human population. Furthermore, drug compatibility with the albumin nanoparticle is remarkable. The robust structure of the nanoparticle, high drug encapsulation, and customisable drug release make it a promising carrier option for the treatment of lung cancer. In this review, we summarise human serum albumin and bovine serum albumin in the targeted delivery of anticancer drugs to lung cancer cells.