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Expedition of liposomes to intracellular targets in solid tumors after intravenous administration
Sarandeep Malhi,Kalpana Dixit,Harmik Sohi,Ranjita Shegokar 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.2
Liposomes as a drug delivery system provides a leading approach for the systemic (intravenous) administration of drugs. Several approaches to kill tumor cells specifically have been developed, but still there is dearth in their selectivity. Among all other nano-carrier systems, liposomal formulations of cytotoxic drugs have received an appreciable recommendation in the form of clinical approvals. Liposomal delivery provides the benefits of reduced toxicity and enhanced efficacy for the treatment of cancer. However, delivery of liposomes to desired cell type with its further trafficking to desired intracellular organelle is a challenging, yet a promising approach for safer cancer therapeutics. Several anatomical-physiological barriers starting from systemic to cellular to intracellular levels are required to be overcome to achieve efficient cancer therapy. This review discusses the barriers associated with the delivery of liposomes from the extracellular to intracellular compartments of a solid tumor and further summarizes the development of liposomal carrier system to overcome these barriers.
Samantha E. Russell,Anna L. Wrobel,Olivia M. Dean,Michael Berk,Seetal Dodd,Chee H. Ng,Gin S. Malhi,Susan M. Cotton,Jerome Sarris,Alyna Turner 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.2
Objective: There is often a shortfall in recovery following treatment for an episode of bipolar disorder (BD). Exploration of participant’s experience provides vital information to enhance statistical outcomes for novel therapy trials. This study used mixed-methods to explore participants’ experience of a trial testing N -acetyl cysteine (NAC) and mitochondrially active nutraceuticals for BD depression. Methods: Case report forms from a randomised controlled trial (RCT) of BD depression (n = 148) were analysed using a pragmatic adaption of grounded theory and thematic analysis. Results: Thematic analysis of 148 study participants indicated numerous changes in participant experience over time. For example, perceived environmental stressors reported by participants decreased over the trial in both treatment groups. Quantitative analysis of the themes revealed more positive theme reports in the combination treatment arm compared to the placebo arm and there were more negative themes identified in the placebo arm, compared to the NAC arm. Conclusion: This approach revealed additional results not elucidated in the primary quantitative analysis. This emphasises the value of mixed-methods research in capturing participants’ experiences in RCTs and detecting possible latent benefits and risks. Such methods can detect latent target signals in novel therapy trials conducted in BD and generate novel hypotheses.
Olivia May Dean,Michael Maes,Melanie Ashton,Lesley Berk,Buranee Kanchanatawan,Atapol Sughondhabirom,Sookjareon Tangwongchai,Chee Ng,Nathan Dowling,Gin S. Malhi,MIchael Berk 대한정신약물학회 2014 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.12 No.3
While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functionalrecovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation ofnovel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotectiveproperties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctivetrial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctivetreatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (witha 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational FunctioningAssessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient GlobalImpression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool(LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide newtreatment targets, both by showing efficacy with a new class of ‘antidepressant’ but also through the analysis of biomarkersthat may further inform our understanding of the pathophysiology of unipolar depression.
Samantha E. Russell,Anna L. Wrobel,Melanie M. Ashton,Alyna Turner,Mohammadreza Mohebbi,MIchael Berk,Sue Cotton,Seetal Dodd,Chee H. Ng,Gin S. Malhi,Olivia M. Dean 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.3
Objective: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. Methods: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (+4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. Results: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. Conclusion: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.
Gerard Anmella,Alcy Meehan,Melanie Ashton,Mohammadreza Mohebbi,Giovanna Fico,Chee H. Ng,Michael Maes,Lesley Berk,Michele De Prisco,Ajeet B. Singh,Gin S. Malhi,Michael Berk,Seetal Dodd,Diego Hidalgo-Ma 대한정신약물학회 2024 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.22 No.1
Objective: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity(illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion: Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.