Design and evaluations of a nanostructured lipid carrier loaded with dopamine hydrochloride for intranasal bypass drug delivery in Parkinson's disease.

AIM: The goal of this study is to optimisation and evaluation of dopamine-loaded NLC (NLC-DOPA) for achieve dopamine concentrations into brain for treatment of Parkinson's disease which causes progressive neuronal death. METHOD: NLC-DOPA prepared by homogenisation method using solid lipids (Cholesterol and Soya lecithin), liquid lipid (Oleic acid) and surfactant (Poloxamer- 188) as major excipients, optimised by central composite design using design expert-13 software. The optimised formulations were characterised by particle size, zeta potential, entrapment efficiency, SEM, TEM, FTIR, DSC, XRD, stability study and in-vitro drug release. The histopathology of rat brain tissues and goat nasal tissues were performed. The ex-vivo (permeability and nasal ciliotoxicity study) and in vivo pharmacodynamics study were also accomplished to determine its efficacy and potency of NLC. RESULT: The NLC-DOPA formulations were optimised in particle size and (EE)% with range from 85.53 ± 0.703 to 106.11 ± 0.822 nm and 82.17 ± 0.794 to 95.45 ± 0.891%, respectively. The optimised formulation F11 showing best goodness-fitted model kinetic, followed by Korsmeyer-Peppas equation and zero order kinetic. The SEM and TEM confirmed the spherical and smooth morphology of formulation. FTIR and DSC spectra were given compatibility of compound and XRD diffractograms confirmed the amorphous nature. An ex-vivo study was showed the high permeability coefficient (6.67*1 0 -4 cm/min, which is twice, compare to pure drug) and there was no damage in nasal mucosa, confirmed by the ciliotoxicity study. In-vivo study was shown significant effects of optimised NLC-DOPA on locomotor activity, force-swimming test and neurochemical assessment using rotenone induced Parkinson's model on Albino Wistar rats. CONCLUSION: NLC-DOPA was prepared and optimised successfully with increased bioavailability of drug from the NLC into brain with reduce toxicity in effective treatment of Parkinson's disease.

Augmented Transdermal Delivery of Curcumin for the Effective Management of Plaque Psoriasis - Design, Formulation, Characterisation, and In Vivo Studies.

Psoriasis is a recurrent, life-threatening anti-inflammatory condition that affects nearly 1-3% of the global population. It is an autoimmune illness distinguished by hyperplasia of skin cells or fast skin cell development, resulting in abnormally irritating scales and skin patches. Curcumin, as a selective phosphorylase kinase inhibitor, actively suppresses inflammation and keratinocyte proliferation in psoriasis. However, limited solubility in water and poor skin permeability poses a significant hurdle in curcumin's topical effectiveness in psoriasis. The present study focuses on enhancing the solubility and skin permeability of curcumin for better transdermal application. Curcumin-loaded invasomes were formulated, and a factorial design was applied to study the effect of the type of terpenes and their concentrations on the properties of prepared invasomes. A topical gel was formulated using the optimised invasomal formulation which was further evaluated for anti-psoriatic potential in BALB/c mice. The optimised formulation showed 85.84 ± 0.56% entrapment efficiency and a vesicle size of 302.33 ± 1.53 nm. The invasomal gel of the optimised formulation showed a permeation flux of 3 times greater than the plain gel. In vivo studies demonstrated that the invasomal gel of curcumin promoted faster and earlier recovery in psoriatic mice than conventional curcumin gel.

An Improvised Deep-Learning-Based Mask R-CNN Model for Laryngeal Cancer Detection Using CT Images.

Recently, laryngeal cancer cases have increased drastically across the globe. Accurate treatment for laryngeal cancer is intricate, especially in the later stages. This type of cancer is an intricate malignancy inside the head and neck area of patients. In recent years, diverse diagnosis approaches and tools have been developed by researchers for helping clinical experts to identify laryngeal cancer effectively. However, these existing tools and approaches have diverse issues related to performance constraints such as lower accuracy in the identification of laryngeal cancer in the initial stage, more computational complexity, and large time consumption in patient screening. In this paper, the authors present a novel and enhanced deep-learning-based Mask R-CNN model for the identification of laryngeal cancer and its related symptoms by utilizing diverse image datasets and CT images in real time. Furthermore, our suggested model is capable of capturing and detecting minor malignancies of the larynx portion in a significant and faster manner in the real-time screening of patients, and it saves time for the clinicians, allowing for more patient screening every day. The outcome of the suggested model is enhanced and pragmatic and obtained an accuracy of 98.99%, precision of 98.99%, F1 score of 97.99%, and recall of 96.79% on the ImageNet dataset. Several studies have been performed in recent years on laryngeal cancer detection by using diverse approaches from researchers. For the future, there are vigorous opportunities for further research to investigate new approaches for laryngeal cancer detection by utilizing diverse and large dataset images.

Translation Research in Therapeutic Approaches from Conventional to Novel Nano-therapeutics for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis is a systemic autoimmune disorder related to joint inflammation, bone erosion, and deformity. Numerous studies indicate that the causes and consequences of RA are still being debated, and therapeutic strategies are in the translation stage. Non-steroidal anti-inflammatory drugs continue to be often used to relieve pain. Still, due to their poor efficacy, failure to halt the spread of the disease, and undesirable adverse effects, they are no longer regarded as first-line treatments. The development of biologic DMRDs designed to reduce the inflammatory response led to substantial changes to the strategy for managing this disease. Although biologic DMRDs have made significant strides in the management of Rheumatoid arthritis, certain patients' lack of response to biological approaches and therapy cessation due to systemic toxicity are unresolved problems. Therefore, to improve the in vivo effect and reduce systemic adverse effects, new approaches are needed to proactively target and transport therapeutic molecules to target sites. The intriguing method of nanotechnology enables the encapsulation of drugs to prevent their deterioration and systemic adverse effects. The next generation of Rheumatoid arthritis therapies might be based on advances in nanomaterial-based drug delivery, Trojan horse, and antibody targeting approaches. This article presents an overview of the advancements in Rheumatoid arthritis therapy, ranging from traditional methods to recent cutting-edge, ongoing pre-clinical and clinical approaches.

Effectiveness of Semecarpus anacardium Linn. fruits in cancer and inflammatory diseases: A mini review.

BACKGROUND: Semecarpus anacardium Linn. (SCA) fruits are found in India's sub-Himalayan, tropical, and central regions and have been utilized for centuries in traditional Indian medicine to treat various ailments. In recent times, a growing body of research has emerged indicating that the extracts and active components found in SCA fruits possess qualities that can potentially inhibit the development of cancer and inflammatory markers. PURPOSE: This study aims to provide a comprehensive review of the existing literature on the pharmacological mechanisms underlying the effects of extracts and phytochemicals of SCA fruits in cellular, animal models, and clinical trials of cancer and inflammatory diseases. METHODS: A comprehensive literature search was conducted utilizing several databases, including PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews using the keywords "Semecarpus anacardium", "Anti-inflammatory," and "cancer". The collection of articles started with establishing the database and continued until April 2024. RESULTS: Out of 1130 retrieved database records, 316 pertained to systematic reviews. The remaining 814 records focused on examining the anticancer and anti-inflammatory properties of SCA fruits. In the course of these investigations, the four primary cancer types linked to SCA fruits are identified as lung cancer, hepatocellular carcinoma, breast cancer, and blood cancer. CONCLUSION: The findings will provide more support for investigating SCA fruits in cancer treatment and will furnish thorough reference data and recommendations for future studies on this botanical medication.

A Comprehensive Review on Liver Targeting: Emphasis on Nanotechnology- based Molecular Targets and Receptors Mediated Approaches.

BACKGROUND: The pathogenesis of hepatic diseases involves several cells, which complicates the delivery of pharmaceutical agents. Many severe liver diseases affecting the worldwide population cannot be effectively treated. Major hindrances or challenges are natural physiological barriers and non-specific targeting of drugs administered, leading to inefficient treatment. Hence, there is an earnest need to look for novel therapeutic strategies to overcome these hindrances. A kind of literature has reported that drug safety and efficacy are incredibly raised when a drug is incorporated inside or attached to a polymeric material of either hydrophilic or lipophilic nature. This has driven the dynamic investigation for developing novel biodegradable materials, drug delivery carriers, target-specific drug delivery systems, and many other novel approaches. OBJECTIVE: Present review is devoted to summarizing receptor-based liver cell targeting using different modified novel synthetic drug delivery carriers. It also highlights recent progress in drug targeting to diseased liver mediated by various receptors, including asialoglycoprotein, mannose and galactose receptor, Fc receptor, low-density lipoprotein, glycyrrhetinic, and bile acid receptor. The essential consideration is given to treating liver cancer targeting using nanoparticulate systems, proteins, viral and non-viral vectors, homing peptides and gene delivery. CONCLUSION: Receptors based targeting approach is one such approach that was explored by researchers to develop novel formulations which can ensure site-specific drug delivery. Several receptors are on the surfaces of liver cells, which are highly overexpressed in various disease conditions. They all are helpful for the treatment of liver cancer.

Lipid nanocarrier of selegiline augmented anti-Parkinson's effect via P-gp modulation using quercetin.

In the present study, SEL was loaded in a lipid nanocarrier (LNC) formulation with a P-gp pump inhibitor i.e., Quercetin (QUR) for improving the bioavailability of the SEL in the brain via the oral route. SEL-QUR LNC was formulated using modified emulsiosonication method and optimized using central composite rotatable design (CCRD) design. The results showed that optimized SEL-QUR LNC formulation was spherical with globule size, polydispersity index, entrapment efficiency and zeta potential within the range of 92.46-95.34 nm, 0.239-0.248, 88.94-91.26%, and -6.21 to -7.75 mV respectively. A 4-fold and 6-fold increase was observed in the permeation of SEL from SEL-QUR LNC across the gut sac in comparison with SEL-QUR and SEL suspensions respectively. CLSM images showed 2-fold deeper permeation of SEL across intestinal membrane demonstrating excellent in vivo prospect of the formulation. The behavioural studies including forced swimming, muscle coordination, locomotor activity, akinesia, and catalepsy were performed in the haloperidol-induced PD rats that demonstrated increased efficacy of the formulation in contrast to the SEL-QUR and SEL suspensions. These studies concluded that developed LNC formulation loaded SEL with P-gp inhibitor had the potential in improving bioavailability of SEL in the brain via oral route.

Recent advances and prospects in gemcitabine drug delivery systems.

Cancer is a community health hazard which progress at a fatal rate in various countries across the globe. An agent used for chemotherapy should exhibit ideal properties to be an effective anticancer medicine. The chemotherapeutic medicines used for treatment of various cancers are, gemcitabine, paclitaxel, etoposide, methotrexate, cisplatin, doxorubicin and 5-fluorouracil. However, many of these agents present nonspecific systemic toxicity that prevents their treatment efficiency. Of all, gemcitabine has shown to be an active agent against colon, pancreatic, colon, ovarian, breast, head and neck and lung cancers in amalgamation with various anticancer agents. Gemcitabine is considered a gold-standard and the first FDA approved agent used as a monotherapy in management of advanced pancreatic cancers. However due to its poor pharmacokinetics, there is need of newer drug delivery system for efficient action. Nanotechnology has shown to be an emerging trend in field of medicine in providing novel modalities for cancer treatment. Various nanocarriers have the potential to deliver the drug at the desired site to obtain information about diagnosis and treatment of cancer. This review highlights on various nanocarriers like polymeric nanoparticles, solid lipid nanoparticles, mesoporous silica nanoparticles, magnetic nanoparticles, micelles, liposomes, dendrimers, gold nanoparticles and combination approaches for delivery of gemcitabine for cancer therapy. The co-encapsulation and concurrent delivery of Gem with other anticancer agents can enhance drug action at the cancer site with reduced side effects.

Applications of Exosomes in Targeted Drug Delivery for the Treatment of Parkinson's Disease: A Review of Recent Advances and Clinical Challenges.

Parkinson's disease (PD) is one of the most prevalent and severe neurodegenerative disease affecting more than 6.1 million people globally. It is characterized by age-related progressive deterioration of neurological functions caused by neuronal damage or neuronal death. During PD, the dopamineproducing cells in the substantia nigra region of the brain degenerate, which leads to symptoms like resting tremors and rigidity. Treatment of PD is very challenging due to the blood-brain barrier, which restricts the drug from reaching the brain. Conventional drug delivery systems possess a limited capacity to cross the blood barrier, leading to low bioavailability and high toxicity (due to off-site drug release). Therefore, it becomes necessary to accelerate the development of novel drug delivery systems, including nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, and solid lipid nanoparticles for the treatment of PD. Exosomes are biological lipid bilayer membrane vesicles produced by nearly all mammalian cells. The characteristics of vesicles are unique to their cell of origin and are primarily involved in intracellular communication. Exosomes, due to their nanoscale size, could easily permeate across the central nervous system, which makes them ideal for targeting the neurons in the substantia nigra. Exosomes could be efficient drug carrier systems for brain targeting, which can increase the efficacy of the drug and minimize the side effects. The review aims at providing a broad updated view of exosomes and their application in the treatment of PD.

Topical delivery of acetazolamide by encapsulating in mucoadhesive nanoparticles.

The intent of this study was to provide topical delivery of acetazolamide by preparing chitosan-STPP (sodium tripolyphosphate) nanoparticles of acetazolamide and evaluate the particle size, zeta potential, drug entrapment, particle morphology; in vitro drug release and in vivo efficacy. The particles showed sustained in vitro drug release which followed the Higuchi kinetic model. The results indicate that the nanoparticles released the drug by a combination of dissolution and diffusion. The optimised formulation was having particle size 188.46 ± 8.53 nm and zeta potential + 36.86 ± 0.70 mV. The particles were spherical with a polydispersity index of 0.22 ± 0.00. Powder X-ray diffraction and differential scanning calorimetry indicated diminished crystallinity of drug in the nanoparticle formulation. In the in vitro permeation study, the nanoparticle formulation showed elevated permeation as compared to that of drug solution with negative signs of corneal damage. In vitro mucoadhesion studies showed 90.34 ± 1.12% mucoadhesion. The in vivo studies involving ocular hypotensive activity in rabbits revealed significantly higher hypotensive activity (P < 0.05) as compared with plain drug solution with no signs of ocular irritation. The stability studies revealed that formulation was quite stable.

Overview of biopolymers as carriers of antiphlogistic agents for treatment of diverse ocular inflammations.

Inflammation of the eye is a usual clinical condition that can implicate any part of the eye. The nomenclature of variety of such inflammations is based on the ocular part involved. These diseases may jeopardize normal functioning of the eye on progression. In general, corticosteroids, antihistamines, mast cell stabilizers and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat inflammatory diseases/disorders of the eye. There have been several attempts via different approaches of drug delivery to overcome the low ocular bioavailability resulting from shorter ocular residence time. The features like safety, ease of elimination and ability to sustain drug release have led to application of biopolymers in ocular therapeutics. Numerous polymers of natural origin such as gelatin, collagen, chitosan, albumin, hyaluronic acid, alginates etc. have been successfully employed for preparation of different ocular dosage forms. Chitosan is the most explored biopolymer amongst natural biopolymers because of its inherent characteristics. The emergence of synthetic biopolymers (like PVP, PACA, PCL, POE, polyanhydrides, PLA, PGA and PLGA) has also added new dimensions to the drug delivery strategies meant for treatment of ophthalmic inflammations. The current review is an endeavor to describe the utility of a variety of biomaterials/polymers based drug delivery systems as carrier for anti-inflammatory drugs in ophthalmic therapeutics.