Assessment of Severity of Substance use for Outcomes Research and Treatment (ASSORT): A substance use severity scale developed and validated across six tertiary care centers in India.

Background and Aims: Assessment of the severity of substance use disorders (SUDs) in a culture-sensitive manner can help gauge the current condition of the substance user and assess change with time. The present study aimed to develop a scale for the assessment of the severity of SUDs in the Indian clinical context. Methods: Based upon the review of literature on previously available instruments and a consultative meeting of experts, a clinician-rated scale was developed that finally comprised 41 items. A briefer 5-item scale with current and lifetime versions was also developed. The scales were applied to patients with SUDs at six different clinical sites. Results: The instrument was applied to 720 patients (98.2% males, mean age: 34.6 years). The Cronbach's alpha of the full scale was 0.852. The inter-rater reliability Pearson correlation coefficient of the full-scale was r = 0.821 (P < 0.001), and the intra-class correlation coefficient single measure was 0.800 (95% confidence interval: 0.724-0.956). A four-factor solution was suggested to be the most tenable. The mean application duration of the full scale was 13.4 minutes, and that of the briefer version was 2 minutes. Conclusion: This validated scale could be a potentially useful assessment measure for the severity of SUDs in the Indian context. The utility lies in the simplicity of administration and scoring and the balance between brevity and thorough assessment.

AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging.

Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies.

Recent Progress and Challenges in Clinical Translation of Nanomedicines in Diagnosis and Treatment of Lung Cancer.

Lung cancer is one of the leading causes of death across the world. There are numerous challenges in the early diagnosis and effective treatment of lung cancer, including developing multidrug resistance. However, the diagnosis of lung cancer could be minimally invasive or non-invasive. Nowadays, nanomedicines offer solutions to several emerging challenges in drug delivery research areas. It has the potential to enhance the therapeutic efficacy of biologically and chemically active agents at the site of action. This approach can also be employed in molecular and cellular imaging, precise and early detection, screening, and targeting drugs for lung cancer treatment. A proper understanding of the disease and timely diagnosis using strategically designed effective nanocarriers can be a promising approach to effectively managing cancer. The present review explores issues related to lung cancer chemotherapy and the promises and hurdles of newer approaches like nanomedicine. The article also summarizes the preclinical studies on diagnosis and treatment, pitfalls, and challenges in the clinical translation of nanomedicines for lung cancer therapy.

Fabrication, in-silico, in-vitro, and in-vivo characterization of transferrin-targeted micelles containing cisplatin and gadolinium for improved theranostic applications in lung cancer therapy.

The targeted delivery of therapeutic and imaging agents is quite challenging in lung cancer therapy. Thus, lung cancer causes high mortality across the world. Herein, we developed TPGS-PF127 micelles containing cisplatin (CDDP) as a model anticancer drug and gadolinium (Gd) as a diagnostic agent by a slightly modified solvent casting method, further, the surface of the micelles was modified using TPGS-transferrin (TPGS-Tf) conjugate to improve targeted delivery of micelles to the lung cancer cells. Prior to this, the binding affinity of Tf over TfR (1E7U) and TfR (1E8W) was investigated with the help of in-silico studies. In-silico results showed good docking scores -7.8 and -7.2 kcal/mol of Tf -ligand towards 1E8W and 1E7U respectively promoting PI3K inhibition. Micelles have shown an average particle size range of 80-200 nm and have shown spherical morphology. The encapsulation efficiency of cisplatin (CDDP) in the CPT, CGPT, and CGPT-Tf micelles ranged from 75.63 % ± 1.58 % to 85.07 % ± 2.65 %. Furthermore, the encapsulation efficiency of gadolinium (Gd) in the CGPT and CGPT-Tf micelles was found to be 67.50 ± 0.32 % and 62.52 ± 0.52 %, respectively. CGPT-Tf micelles exhibited sustained release fashion for CDDP up to 48 h in physiological conditions. In the cytotoxicity study, CGPT-Tf micelles achieved higher cytotoxicity and caused a more antiproliferative effect in A549 cells compared to a commercial CDDP injection (Ciszest 50), after 24 h of treatment. Furthermore, the pharmacokinetic studies have proven the pharmacological effectiveness of developed CGPT-Tf micelles by achieving higher Cmax, Tmax, t1/2, and MRT of CDDP in systemic circulation compared to its counterparts and Ciszest 50. In lung theranostic observations, a higher internalization of Gd was noted in CGPT-TF compared to free Gd. The biochemical studies have proved the biocompatibility of developed micelles formulations by showing no sign of toxicity in the lungs. The developed micelles have great potential to be utilized in treating and diagnosing a wide variety of cancers.

An Overview of Current Progress and Challenges in Brain Cancer Therapy Using Advanced Nanoparticles.

Brain tumors pose significant challenges in terms of complete cure and early-stage prognosis. The complexity of brain tumors, including their location, infiltrative nature, and intricate tumor microenvironment (TME), contributes to the difficulties in achieving a complete cure. The primary objective of brain cancer therapy is to effectively treat brain tumors and improve the patient's quality of life. Nanoparticles (NPs) have emerged as promising tools in this regard. They can be designed to deliver therapeutic drugs to the brain tumor site while also incorporating imaging agents. The NPs with the 10-200 nm range can cross the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) and facilitate drug bioavailability. NPs can be designed by several methods to improve the pharmaceutical and pharmacological aspects of encapsulated therapeutic agents. NPs can be developed in various dosage forms to suit different administration routes in brain cancer therapy. The unique properties and versatility of NPs make them essential tools in the fight against brain tumors, offering new opportunities to improve patient outcomes and care. Having the ability to target brain tumors directly, overcome the BBB, and minimize systemic side effects makes NPs valuable tools in improving patient outcomes and care. The review highlights the challenges associated with brain tumor treatment and emphasizes the importance of early detection and diagnosis. The use of NPs for drug delivery and imaging in brain tumors is a promising approach to improving patient outcomes and quality of life. The versatility and unique properties of NPs make them valuable tools in the fight against brain tumors, and NPs have the potential to revolutionize healthcare.

Dual-targeted transferrin and AS1411 aptamer conjugated micelles for improved therapeutic efficacy and imaging of brain cancer.

Brain tumors represent an aggressive form of cancer, posing significant challenges in achieving complete remission. Development of advanced therapies is crucial for improving clinical outcomes in cancer patients. This study aimed to create a novel treatment approach using dual-targeted transferrin (TF) and AS1411 conjugated micelles, designed to enhance therapeutic effectiveness of docetaxel (DTX) and facilitate gadolinium (Gd) based imaging in brain cancer. Micelles were prepared using a slightly modified solvent-casting method, and the dual-targeting ligands were attached to the micelle's surface through a physical adsorption process. Average particle size of micelles ranged from 117.49 ± 3.90-170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from - 1.5 ± 0.02 to - 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in micelles varied from 92.64 ± 4.22-79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in micelles was found to be 48.27 ± 3.18-58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411 micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411 micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 µg/ml compared to Taxotere® (2.73 ± 0.73 µg/ml). Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411 micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411 micelles exhibited 23.79 ± 17.82 µg.h/ml higher than Taxotere® (14.14 ± 10.59 µg.h/ml). These findings direct enhanced effectiveness in brain cancer therapy leading to improved therapeutics in brain cancer patients. The combined targeted ligands and therapeutic agents strategy can direct advancement in brain cancer therapy and offer improved therapy for patients.

RGD-decorated PLGA nanoparticles improved effectiveness and safety of cisplatin for lung cancer therapy.

Upon extensive pharmaceutical and biomedical research to treat lung cancer indicates that lung cancer remains one of the deadliest diseases and the leading cause of death in men and women worldwide. Lung cancer remains untreated and has a high mortality rate due to the limited potential for effective treatment with existing therapies. This highlights the urgent need to develop an effective, precise and sustainable solutions to treat lung cancer. In this study, we developed RGD receptor-targeted PLGA nanoparticles for the controlled and targeted co-delivery of cisplatin (CDDP) and upconversion nanoparticles (UCNP) in lung cancer therapy. Pluronic F127-RGD conjugate was synthesized by carbodiimide chemistry method and the conjugation was confirmed by FTIR and 1HNMR spectroscopy techniques. PLGA nanoparticles were developed by the double emulsification method, then the surface of the prepared nanoparticles was decorated with Pluronic F127-RGD conjugate. The prepared formulations were characterized for their particle size, polydispersity index, zeta potential, surface morphology, drug encapsulation efficiency, and in vitro drug release and haemolysis studies. Pharmacokinetic studies and safety parameters in BAL fluid were assessed in rats. Histopathology of rat lung tissue was performed. The obtained results of particle sizes of the nanoparticle formulations were found 100-200 nm, indicating the homogeneity of dispersed colloidal nanoparticles formulations. Transmission Electron Microscopy (TEM) revealed the spherical shape of the prepared nanoparticles. The drug encapsulation efficiency of PLGA nanoparticles was found to range from 60% to 80% with different nanoparticles counterparts. RGD receptor-targeted PLGA nanoparticles showed controlled drug release for up to 72 h. Further, RGD receptor-targeted PLGA nanoparticles achieved higher cytotoxicity in compared to CFT, CFT, and Ciszest-50 (marketed CDDP injection). The pharmacokinetic study revealed that RGD receptor-targeted PLGA nanoparticles were 4.6-fold more effective than Ciszest-50. Furthermore, RGD receptor-targeted PLGA nanoparticles exhibited negligible damage to lung tissue, low systemic toxicity, and high biocompatible and safety in lung tissue. The results of RGD receptor-targeted PLGA nanoparticles indicated that it is a promising anticancer system that could further exploited as a potent therapeutic approach for lung cancer.

Evaluation of paxillin expression in patients with oral squamous cell carcinoma: An immunohistochemical study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the tenth most common cancer in the world. The diagnosis of OSCC remains problematic, especially in advanced-stage tumors. AIMS: The present study was conducted to understand the pattern of expression of paxillin in varying grades of carcinomas and also to ascertain whether its expression has an association with increasing grades. METHODS: A total of ninety formalin-fixed paraffin-embedded tissues of OSCC were included in the study comprising thirty cases of each of well-differentiated squamous cell carcinomas, moderately differentiated squamous cell carcinomas (MDSCCs) and poorly differentiated squamous cell carcinomas (PDSCCs). The tissue sections were subjected to immunohistochemical staining of paxillin using super polymer-sensitive polymer 3,3' diaminobenzidine detection kit. All the three groups were analyzed on various parameters including staining intensity, location and percentage of staining. SPSS 19.0 was used to analyze the data. RESULTS: Paxillin stain positivity was observed in 95.5% of the cases. Predominant intense paxillin staining was demonstrated in 17 (56.6%) cases of well-differentiated squamous cell carcinoma, 28 (93.3%) cases of moderately differentiated squamous squamous cell carcinoma and 15 (50%) cases of PDSCC. A predominant cytoplasmic staining was observed in 21 (70%) cases of PDSCC and cytoplasmic plus membrane staining in 14 (46.6%) cases of MDSCC. CONCLUSION: The present study provides evidence that paxillin may be involved in the development and progression of OSCC. Thus, paxillin could be considered a useful biomarker for patient management and prognosis.