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Illuminating Insights: Clinical Study Harnessing Pharmacoscintigraphy for Permeation Study of Radiolabeled Nimesulide Topical Formulation in Healthy Human Volunteers

Sharma N, Khanna K, Kumar N, Karwasra R, Janakiraman AK, Rajagopal MS

Assay Drug Dev Technol, 2023 Oct;21(7):325-330.
PMID: 37801663 DOI: 10.1089/adt.2023.053

An alternative to oral administration for the delivery of therapeutic substances is the topical route, which frequently has comparable efficacy but may have a better tolerability profile. Gamma scintigraphy is a noninvasive technique that involves the application of radioactive substances to conduct biodistribution studies of therapeutic substances delivered through various routes. Nimesulide (NSD) was radiolabeled with technetium pertechnetate (Technetium99m [99mTc]) and this radiolabeled drug complex (99mTc-NSD) was used to prepare a topical gel formulation. The permeation of the radiolabeled drug from the topical gel was determined by gamma scintigraphy on human volunteers. The region of interest was calculated for the quantification of permeated radiolabeled drugs. This was observed that the mean percentage permeation of 99mTc-NSD was found to be 0.32 ± 0.22 to 36.37 ± 2.86 at 5 and 240 min. It was demonstrated that gamma scintigraphy may be a noninvasive and reliable technique for the determination of drug permeation through topical routes.
Hyaluronic acid-functionalized lipoplexes and polyplexes as emerging nanocarriers for receptor-targeted cancer therapy

Chandra J, Molugulu N, Annadurai S, Wahab S, Karwasra R, Singh S, et al.

Environ Res, 2023 Sep 15;233:116506.
PMID: 37369307 DOI: 10.1016/j.envres.2023.116506

Cancer is an intricate disease that develops as a response to a combination of hereditary and environmental risk factors, which then result in a variety of changes to the genome. The cluster of differentiation (CD44) is a type of transmembrane glycoprotein that serves as a potential biomarker for cancer stem cells (CSC) and viable targets for therapeutic intervention in the context of cancer therapy. Hyaluronic acid (HA) is a linear polysaccharide that exhibits a notable affinity for the CD44 receptor. This characteristic renders it a promising candidate for therapeutic interventions aimed at selectively targeting CD44-positive cancer cells. Treating cancer via non-viral vector-based gene delivery has changed the notion of curing illness through the incorporation of therapeutic genes into the organism. The objective of this review is to provide an overview of various hyaluronic acid-modified lipoplexes and polyplexes as potential drug delivery methods for specific forms of cancer by effectively targeting CD44.
Exploring nalbuphine loaded chitosan nanoparticles for effective pain management through intranasal administration: a comparative study

Khanna K, Sharma N, Karwasra R, Kumar A, Nishad DK, Janakiraman AK, et al.

J Drug Target, 2024 Sep 04.
PMID: 39229894 DOI: 10.1080/1061186X.2024.2397800

BACKGROUND: Intranasal drug delivery shows potential for brain access via olfactory and trigeminal routes.
PURPOSE: This work aimed to ensure brain availability of nalbuphine via the nasal route.
METHOD: Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised.
RESULT: SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management.
Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies

Sharma N, Kurmi BD, Singh D, Mehan S, Khanna K, Karwasra R, et al.

J Drug Target, 2024 Feb 19.
PMID: 38328920 DOI: 10.1080/1061186X.2024.2316785

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.