scholarly journals PLGA/PLA-Based Long-Acting Injectable Depot Microspheres in Clinical Use: Production and Characterization Overview for Protein/Peptide Delivery

2021 ◽  
Vol 22 (16) ◽  
pp. 8884
Author(s):  
Arun Butreddy ◽  
Rajendra Prasad Gaddam ◽  
Nagavendra Kommineni ◽  
Narendar Dudhipala ◽  
Chandrashekhar Voshavar
Keyword(s):  
Double Emulsion ◽  
Physicochemical Characteristics ◽  
Therapeutic Effects ◽  
Clinical Use ◽  
Drug Plasma ◽  
Dosing Frequency ◽  
Manufacturing Techniques ◽  
Long Acting ◽  
End Group ◽  
Proteins And Peptides

Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are encapsulated in the microspheres to increase their bioavailability and provide a long release period (days or months) with constant drug plasma concentration. The biodegradable and biocompatible properties of PLGA/PLA polymers, including but not limited to molecular weight, end group, lactide to glycolide ratio, and minor manufacturing changes, could greatly affect the quality attributes of microsphere formulations such as release profile, size, encapsulation efficiency, and bioactivity of biopharmaceuticals. Besides, the encapsulated proteins/peptides are susceptible to harsh processing conditions associated with microsphere fabrication methods, including exposure to organic solvent, shear stress, and temperature fluctuations. The protein/peptide containing LAI microspheres in clinical use is typically prepared by double emulsion, coacervation, and spray drying techniques. The purpose of this review is to provide an overview of the formulation attributes and conventional manufacturing techniques of LAI microspheres that are currently in clinical use for protein/peptides. Furthermore, the physicochemical characteristics of the microsphere formulations are deliberated.

Lipospheres: Emerging Carriers in the Delivery of Proteins and Peptides

1970 ◽  
Vol 1 (3) ◽  
pp. 207-214
Author(s):  
Manju Rawat ◽  
Swarnlata Saraf
Keyword(s):  
Drug Delivery ◽  
Protein Stability ◽  
Biodegradable Polymers ◽  
Clinical Utility ◽  
Physicochemical Characteristics ◽  
Peptide Delivery ◽  
Chemical Instabilities ◽  
Physical And Chemical ◽  
Proteins And Peptides

Currently, drug delivery technologies for protein and peptide delivery mainly rely on biodegradable polymers. However, protein stability during release from these systems can be critical due to physical and chemical instabilities. Lipospheres are solid microparticles composed of fat core stabilized by phospholipids layer represent an alternative carrier for the delivery of highly challenging, labile and unstable  substances. This review highlights various aspects of lipospheres like physicochemical characteristics and stability for better clinical utility with a wider spectrum of proteins and peptides.

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for Their Use as an Add-on Therapy in Schizophrenia

2020 ◽  
Vol 26 ◽  
Author(s):  
Felix-Martin Werner ◽  
Rafael Coveñas
Keyword(s):  
Clinical Trials ◽  
Maintenance Therapy ◽  
Antipsychotic Drug ◽  
Cognitive Functions ◽  
Antipsychotic Drugs ◽  
Psychotic Disorders ◽  
Therapeutic Effects ◽  
Treatment Resistant ◽  
Long Acting ◽  
Novel Antipsychotic

Background: Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders and, in this case, they can be treated with clozapine. In these patients and based on previous reviews on novel antipsychotic drugs, it is important to know whether an add-on therapy with new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. Objective: The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of current available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. Results: The mechanisms of action, the therapeutic effects and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole and lumateperone are up-dated. Published case reports of patients with treatmentresistant psychoses are also discussed. These patients were treated with clozapine but a high PANSS total score was observed. Only an add-on therapy with cariprazine improved the score and, above all, negative schizophrenic symptoms and cognitive functions. To ensure a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs may be a choice for a maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, are being investigated in preclinical and clinical trials. Conclusion: In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether a combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are a safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by an add-on therapy with cognition enhancing drugs.

Clinical Use of Toxic Proteins and Peptides from Tian Hua Fen and Scorpion Venom

2019 ◽  
Vol 20 (3) ◽  
pp. 285-295
Author(s):  
Chen Ling ◽  
Yuanhui Zhang ◽  
Jun Li ◽  
Wenli Chen ◽  
Changquan Ling
Keyword(s):  
Herbal Medicines ◽  
Scorpion Venom ◽  
The Other ◽  
Western World ◽  
Chinese Government ◽  
Clinical Use ◽  
Potential Benefits ◽  
Scientific Results ◽  
Proteins And Peptides ◽  
Toxic Proteins

Traditional Chinese Medicine (TCM) has been practiced in China for thousands of years. As a complementary and alternative treatment, herbal medicines that are frequently used in the TCM are the most accepted in the Western world. However, animal materials, which are equally important in the TCM practice, are not well-known in other countries. On the other hand, the Chinese doctors had documented the toxic profiles of hundreds of animals and plants thousand years ago. Furthermore, they saw the potential benefits of these materials and used their toxic properties to treat a wide variety of diseases, such as heavy pain and cancer. Since the 50s of the last century, efforts of the Chinese government and societies to modernize TCM have achieved tremendous scientific results in both laboratory and clinic. A number of toxic proteins have been isolated and their functions identified. Although most of the literature was written in Chinese, this review provide a summary, in English, regarding our knowledge of the clinical use of the toxic proteins isolated from a plant, Tian Hua Fen, and an animal, scorpion, both of which are famous toxic prescriptions in TCM.

Clinical use of the long acting somatostatin analogue octreotide in pediatrics

1994 ◽  
Vol 153 (5) ◽  
pp. 304-310 ◽  
Author(s):  
M. T. Tauber ◽  
A. G. Harris ◽  
P. Rochiccioli
Keyword(s):  
Somatostatin Analogue ◽  
Clinical Use ◽  
Long Acting ◽  
Analogue Octreotide

scholarly journals Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis

2017 ◽  
Vol 43 (4) ◽  
pp. 302-312 ◽  
Author(s):  
Israel Silva Maia ◽  
Mariângela Pimentel Pincelli ◽  
Victor Figueiredo Leite ◽  
João Amadera ◽  
Anna Maria Buehler
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Therapeutic Effects ◽  
Muscarinic Antagonists ◽  
Serious Adverse Events ◽  
Exacerbation Rate ◽  
Copd Exacerbations ◽  
Long Acting

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

scholarly journals Efficacy and Safety of Modified Bushen Yiqi Formulas(MBYF) as Add-On To Formoterol and Budesonide in The Management of COPD: Study Protocol for A Multi-Center, Double-Blinded, Placebo-Controlled, Parallel-Group, Randomized Clinical Trial

2021 ◽  
Author(s):  
Qing Kong ◽  
Yuxue Cao ◽  
Zhen Gao ◽  
Jing Sun ◽  
Hongying Zhang ◽  
...  
Keyword(s):  
Pulmonary Function Tests ◽  
Therapeutic Effects ◽  
Efficacy And Safety ◽  
Bode Index ◽  
Parallel Group ◽  
Registration Number ◽  
Long Acting ◽  
Exacerbation Of Copd ◽  
Double Blinded ◽  
Tcm Syndrome

Abstract Introduction Inhaled glucocorticoid Corticosteroids(ICS), long-acting β2-adrenoceptor agonists(LABA)and other drugs have limited therapeutic effects on COPD with significant individual differences. Traditional Chinese Medicine (TCM) modified Bushen Yiqi formulas༈MBYF༉demonstrates advantages in COPD management in China. This study aims to confirm the related genes affecting the therapeutic effect in the treatment of COPD and evaluate the efficacy and safety of MBYF as an add-on to budesonide/ formoterol on COPD patients. Methods and analysis In this multicenter, randomized, double-blinded, placebo-controlled, parallel-group study, eligible patients with COPD will randomly receive 360-day placebo or MBYF as an add-on to budesonide/ formoterol in 1:1 ratio, and followed-up bimonthly. The primary outcomes are frequency, times and severity of acute exacerbation of COPD (AECOPD), COPD assessment test (CAT) score, pulmonary function tests(PFTs). The secondary outcomes include the modified medical research council (mMRC) dyspnea scale、six minutes walking test (6MWT)、BODE index、quantitative scores of TCM syndrome、inflammation indexes and hypothalamic pituitary adrenaline (HPA) axis function. We also test the genotype to find the relationship between drugs and efficacy. All the data will be recorded in case report forms(CRFs) and analyzed by SPSS V.20.0. Trial registration number ChiCTR1900026124, Prospective registration. Protocol version 2019-09-15

scholarly journals Impact of herbal drugs and its clinical application

2019 ◽  
Vol 10 (2) ◽  
pp. 1340-1345
Author(s):  
Vetriselvan Subramaniyan ◽  
Saminathan Kayarohanam ◽  
Ashok Kumar J ◽  
Vinoth Kumarasamy
Keyword(s):  
Health Care Professionals ◽  
Herbal Medicines ◽  
Drug Formulation ◽  
Therapeutic Effects ◽  
Clinical Use ◽  
Herbal Drugs ◽  
Herbal Drug ◽  
Alternative Medicines ◽  
Ancient Times ◽  
The Impact

Since ancient times until now exploring the importance of herbal medicines to treat the variety of diseases. Currently the herbal medicines searching for health, wellness and aim to achieve effective treatment without much side effect. Recent days the impact of herbal medicines well established even herbal treatment is one of the alternative medicines for most of the diseases such as hyperlipidemia, diabetes mellitus etc. Medicinal plants always have been rich sources of bioactive compounds, and that will be very helpful to human health. The reasons for herbal medicines attracted by the health care professionals and common individuals, including concern about confidence and safety of drugs. Allopathic medicines have many side effects and sometimes failing to treat and most of the herbal drugs proven better therapeutic effects without any major adverse effects. With the demand for phytomedicine user, this review highlights modern herbal drug formulation and its clinical use.

scholarly journals What is a Therapeutic Potential of N-Acetylcysteine in Lung Silicosis?

2021 ◽  
Vol 21 (3) ◽  
pp. 80-89
Author(s):  
Adamcakova Jana ◽  
Mokra Daniela
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Silicon Dioxide ◽  
Pulmonary Disease ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Clinical Use ◽  
Fundamental Factor ◽  
Long Term Experience

Abstract Lung silicosis is a serious pulmonary disease caused by an exposure of lung to inhaled silicon dioxide (SiO2) or silica. Although pathomechanisms of the disease have not been fully elucidated, oxidative stress has been recognized as a fundamental factor triggering a fibrotizing inflammation leading to irreversible changes in lung tissue. Based on this knowledge, therapeutic potential of various antioxidants has been intensively discussed. Among them, N-acetylcysteine with its multiple anti-inflammatory and antioxidant actions and a long-term experience with its clinical use in various diseases appears as a very promising choice. The purpose of this article is to review the therapeutic effects of N-acetylcysteine particularly in relation to a lung injury and to point out a potential of N-acetylcysteine in the treatment of lung silicosis.

scholarly journals 2499. Perceptions of and Preferences for Oral or Long-Acting Injectable Antiretroviral Treatment Regimens in the United States and Canada

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S866-S867
Author(s):  
Cindy Garris ◽  
Sebastian Heidenreich ◽  
Erin Arthurs ◽  
Frank Spinelli ◽  
Katelyn Cutts ◽  
...  
Keyword(s):  
United States ◽  
Online Survey ◽  
Antiretroviral Treatment ◽  
The United States ◽  
Physician Satisfaction ◽  
Treatment Preferences ◽  
Cross Sectional ◽  
Pilot Survey ◽  
Dosing Frequency ◽  
Long Acting

Abstract Background Antiretroviral treatment (ART) for patients living with HIV (PLHIV) has improved greatly, however, challenges with daily oral dosing remain. New ART options with reduced dosing frequency and innovative delivery methods may help address these challenges. This study assesses patient and physician satisfaction with current treatments and preferences for switching to a monthly or every other month long-acting injectable (LAI) ART. Methods This is a cross-sectional online survey of PLHIV and physicians treating PLHIV in United States and Canada. A literature review, clinical expert input, and qualitative and quantitative pilots informed survey design. Eligible PLHIV were on ART for ≥ 6 months and virally suppressed (self-reported). Survey questions for patients evaluate satisfaction and adherence to current ART. Treatment preferences are assessed using a discrete choice experiment (DCE), where respondents choose between staying on current ART, switching to another oral ART or switching to a LAI ART. DCE treatment attributes include dosing frequency, side effects, forgivability, food/mealtime restrictions, and mode of administration. Pilot data for US patients is included here; the main survey will include approximately 550 patients and 450 physicians. Results Of 51 PLHIV completing the pilot survey, 80% were male, mean age was 54 years, and 63% were on ART for ≥10 years. Switching ART was common, with 55% reporting changing their ART ≥ 3 times. Just under half of patients (47%) were not totally satisfied with their current ART. Most common reasons for dissatisfaction included daily reminder of having HIV (31%) and having to take medicine every day (28%). Just over a quarter of patients (28%) reported forgetting to take their ART in the prior month. Across all DCE choices, patients preferred to remain on their current treatment 47% of the time, while 45% of the time patients preferred switching to the LAI, and for the remaining 8%, patients chose switching to another oral ART regimen. Conclusion Despite advances in ART, treatment challenges remain. Among the treatment-experienced PLHIV in this pilot survey, over half of their choices resulted in switching to an alternative regimen, and when opting to switch, most patients preferred the long-acting injectable treatment regimen. Disclosures All authors: No reported disclosures.

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