Pub Date : 2024-01-25DOI: 10.2174/0122103031273803231221070539
Prativa Das, Jyanaranjan Panda, K. C. Panigrahi, Ch. Niranjan Patra, G. Jena
Schizophrenia is a chronic disease with acute psychotic symptoms, which is having frequent recurrence. Paliperidone palmitate (PP) is a second-generation antipsy-chotic drug to treat schizophrenia. The aim of the study was to prepare lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD). The primary objective of the current research work was to develop a lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD) to improve its oral bioa-vailability and stability. Optimization using D-Optimal Mixture Design DMD) was conducted, and optimized NEDDS was further lyophilized to improve stability. The lyophilized optimized NEDDS was fur-ther evaluated for biopharmaceutical evaluation. A saturation solubility study revealed Peceol, Tween 80, and Plurol Olique CC497 as suitable candidates for oil, surfactant, and co-surfactant, respectively. Optimized NEDDS of PD showed mean globule size (MGS) of 185 nm, PDI of 0.27 and cumulative % drug release within 15 min Q15 of 86.6%. Lyophilized optimized NEDDS was found to have no significant change in quality attributes within the stability study period. A pharmacokinetic study revealed more than two-fold increases in bioavailability for lyophilized optimized NEDDS. Hence, lyophilized NEDDS of PD can be used as an effective approach for the im-provement of oral bioavailability and stability.
{"title":"D-Optimal Mixture Design Enabled Development of Lyophilized Nanoemulsifying Drug Delivery System of Paliperidone","authors":"Prativa Das, Jyanaranjan Panda, K. C. Panigrahi, Ch. Niranjan Patra, G. Jena","doi":"10.2174/0122103031273803231221070539","DOIUrl":"https://doi.org/10.2174/0122103031273803231221070539","url":null,"abstract":"\u0000\u0000Schizophrenia is a chronic disease with acute psychotic symptoms, which is having frequent recurrence. Paliperidone palmitate (PP) is a second-generation antipsy-chotic drug to treat schizophrenia.\u0000\u0000\u0000\u0000The aim of the study was to prepare lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD).\u0000\u0000\u0000\u0000The primary objective of the current research work was to develop a lyophilized nanoemulsifying drug delivery system (NEDDS) of paliperidone (PD) to improve its oral bioa-vailability and stability.\u0000\u0000\u0000\u0000Optimization using D-Optimal Mixture Design DMD) was conducted, and optimized NEDDS was further lyophilized to improve stability. The lyophilized optimized NEDDS was fur-ther evaluated for biopharmaceutical evaluation.\u0000\u0000\u0000\u0000A saturation solubility study revealed Peceol, Tween 80, and Plurol Olique CC497 as suitable candidates for oil, surfactant, and co-surfactant, respectively. Optimized NEDDS of PD showed mean globule size (MGS) of 185 nm, PDI of 0.27 and cumulative % drug release within 15 min Q15 of 86.6%. Lyophilized optimized NEDDS was found to have no significant change in quality attributes within the stability study period. A pharmacokinetic study revealed more than two-fold increases in bioavailability for lyophilized optimized NEDDS.\u0000\u0000\u0000\u0000Hence, lyophilized NEDDS of PD can be used as an effective approach for the im-provement of oral bioavailability and stability.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139598710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the current scenario, most of the population affected by neurogenera-tive disorders like Alzheimer's, Parkinson's, Huntington's, etc., exist among the 10% population 65 years of age group. Neurodegenerative diseases are characterised as chronic and progressive disorders that occur due to the degeneration of neurons. Baicalein is a flavonoid glycoside derived from the roots of Scutellaria baicalensis. Earlier research suggested that it could be used to treat neurodegenerative illnesses. Baicalein, which was selected for the current study, was designed in-to a solid lipid nanoparticle (SLN) formulation. The SLNs have low permeability across BBB and are delivered by the non-invasive route, i.e., through nasal delivery. The In-silico docking studies were performed to examine and compare the binding affinity of Baicalein to already established drugs on the two most viable targets of Alzheimer's disease, i.e., Beta- secretase and Acetylcho-linesterase. The current work is to formulate and evaluate the Baicalein-loaded SLN for neuro-degenerative disorders via a non-invasive route. Baicalein loaded SLN was developed by solvent emulsification diffusion method, and formulation is characterised by using different parameters such as particle size analysis, zeta po-tential, scanning electron microscope, transverse electron microscope, X-ray diffraction, Differen-tial scanning calorimetric, Fourier transforms -infrared radiations, drug entrapment, in-vitro drug release and in-silico docking studies. The particle size of Baicalein-loaded SLN was 755.2 ± 0.48 nm, the Polydispersity index was 0.06, and the zeta potential was -32.5 ± 0.36 mV. The drug entrapment and loading efficien-cy of the optimised formulation were found to be 94% ± 0.653 and 18.2% ± 0.553, respectively. Optimised formulation shows 84.6% ± 0.3% of drug release within 30 minutes, which demon-strates the sustained release of the drug. Baicalein-loaded SLN is formulated and evaluated for the treatment of neurodegen-erative disorders. SLN is an approach to overcome the challenge of bypassing the BBB by admin-istering the drug via an intranasal route. Hence, when analysed together with the results of Bai-calein-loaded SLN and in-silico studies, it was correlated that Baicalein proved to have a targeted moiety for neurodegeneration.
{"title":"In-vitro and In-silico Examinations on Baicalein-loaded Solid Lipid Nanoparticles for Neurodegeneration","authors":"Mansi Varshney, Bhavna Kumar, Poorvi Varshney, Diwya Kumar Lal, N. Sethiya","doi":"10.2174/0122103031263883231230085819","DOIUrl":"https://doi.org/10.2174/0122103031263883231230085819","url":null,"abstract":"\u0000\u0000In the current scenario, most of the population affected by neurogenera-tive disorders like Alzheimer's, Parkinson's, Huntington's, etc., exist among the 10% population 65 years of age group. Neurodegenerative diseases are characterised as chronic and progressive disorders that occur due to the degeneration of neurons. Baicalein is a flavonoid glycoside derived from the roots of Scutellaria baicalensis. Earlier research suggested that it could be used to treat neurodegenerative illnesses. Baicalein, which was selected for the current study, was designed in-to a solid lipid nanoparticle (SLN) formulation. The SLNs have low permeability across BBB and are delivered by the non-invasive route, i.e., through nasal delivery. The In-silico docking studies were performed to examine and compare the binding affinity of Baicalein to already established drugs on the two most viable targets of Alzheimer's disease, i.e., Beta- secretase and Acetylcho-linesterase.\u0000\u0000\u0000\u0000The current work is to formulate and evaluate the Baicalein-loaded SLN for neuro-degenerative disorders via a non-invasive route.\u0000\u0000\u0000\u0000Baicalein loaded SLN was developed by solvent emulsification diffusion method, and formulation is characterised by using different parameters such as particle size analysis, zeta po-tential, scanning electron microscope, transverse electron microscope, X-ray diffraction, Differen-tial scanning calorimetric, Fourier transforms -infrared radiations, drug entrapment, in-vitro drug release and in-silico docking studies.\u0000\u0000\u0000\u0000The particle size of Baicalein-loaded SLN was 755.2 ± 0.48 nm, the Polydispersity index was 0.06, and the zeta potential was -32.5 ± 0.36 mV. The drug entrapment and loading efficien-cy of the optimised formulation were found to be 94% ± 0.653 and 18.2% ± 0.553, respectively. Optimised formulation shows 84.6% ± 0.3% of drug release within 30 minutes, which demon-strates the sustained release of the drug.\u0000\u0000\u0000\u0000Baicalein-loaded SLN is formulated and evaluated for the treatment of neurodegen-erative disorders. SLN is an approach to overcome the challenge of bypassing the BBB by admin-istering the drug via an intranasal route. Hence, when analysed together with the results of Bai-calein-loaded SLN and in-silico studies, it was correlated that Baicalein proved to have a targeted moiety for neurodegeneration.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139596939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-22DOI: 10.2174/0122103031273192240102054301
Rajni Bala, D. S. Malik, R. Madaan, Shammy Jindal, Vimanpreet Kaur
Intranasal administration has proven to be a viable alternative for local and systemic delivery of varied therapeutic agents. This route has been potentially researched for delivering polar compounds, vaccines, hormones, peptides, proteins, etc. Being non-invasive and painless with a fast onset of action (both local and systemic), intranasal has become an ideal route for medication to children. This route is specifically employed for the delivery of drugs that are unstable in GIT, which gets significantly degraded or metabolized by the first-pass effect. The nasal route's high absorption and permeability profile has led to its exploration as a substitute for parenteral delivery. This paper reviews the feasibility and potentials of intranasal administration, discussing its benefits, drawbacks, market analysis, factors affecting nasal drug delivery system, conventional and novel strategies (polymeric and nano-carrier-based delivery systems) to improve nasal absorption and its clinical management of varied systemic and topical disorders viz. neurodegenerative, pulmonary, microbial, neoplastic, etc.
{"title":"Intranasal Route an Alternative Approach for Systemic Drug Delivery:\u0000Recent Strategies and Progression","authors":"Rajni Bala, D. S. Malik, R. Madaan, Shammy Jindal, Vimanpreet Kaur","doi":"10.2174/0122103031273192240102054301","DOIUrl":"https://doi.org/10.2174/0122103031273192240102054301","url":null,"abstract":"\u0000\u0000Intranasal administration has proven to be a viable alternative for local and systemic\u0000delivery of varied therapeutic agents. This route has been potentially researched for delivering polar compounds, vaccines, hormones, peptides, proteins, etc. Being non-invasive and painless with\u0000a fast onset of action (both local and systemic), intranasal has become an ideal route for medication to children. This route is specifically employed for the delivery of drugs that are unstable in\u0000GIT, which gets significantly degraded or metabolized by the first-pass effect. The nasal route's\u0000high absorption and permeability profile has led to its exploration as a substitute for parenteral delivery. This paper reviews the feasibility and potentials of intranasal administration, discussing its\u0000benefits, drawbacks, market analysis, factors affecting nasal drug delivery system, conventional\u0000and novel strategies (polymeric and nano-carrier-based delivery systems) to improve nasal absorption and its clinical management of varied systemic and topical disorders viz. neurodegenerative, pulmonary, microbial, neoplastic, etc.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139606612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-08DOI: 10.2174/0122103031269368231222095135
Gouri Prasad Nanda, Mrunali Patel, Rashmin B. Patel
Nitrofurantoin is an antimicrobial drug, highly effective in the treatment of critical or chronic bacterial infections of the urinary tract, and hence, it is the first line choice of drug for the treatment of urinary tract infections (UTI). Although the molecule is legacy in nature, there are many challenges in terms of drug product formulation and efficacy thereof. The authors are mainly focused in this literature review on, but not limited to, understanding the molecule in terms of physico-chemical properties of the drug, pharmacokinetics and pharmacodynamics, approved and withdrawn formulations, challenges concerning drug formulation, the cause of drug shortage in the market, improvement areas in terms of formulation and its therapeutic effectiveness. The authors found during their widespread review that the major challenge in the existing conventional drug delivery system of nitrofurantoin is the fluctuation of plasma concentration owing to its variability in drug absorption. Further, they understood that the variability in absorption is due to inherent variability in particle size distribution. Based on the findings, authors also explored the possibilities to deliver the drug in novel drug delivery systems such as nano self-emulsifying emulsions, nanoemulsions and multiple emulsions where the drug can be presented in soluble form and hence the variability in absorption and fluctuation in plasma concentration of drug can be avoided and described briefly the salient features of each drug delivery in this review.
{"title":"Revolutionizing Nitrofurantoin Delivery: Unraveling Challenges and\u0000Pioneering Solutions for Enhanced Efficacy in UTI Treatment","authors":"Gouri Prasad Nanda, Mrunali Patel, Rashmin B. Patel","doi":"10.2174/0122103031269368231222095135","DOIUrl":"https://doi.org/10.2174/0122103031269368231222095135","url":null,"abstract":"\u0000\u0000Nitrofurantoin is an antimicrobial drug, highly effective in the treatment of critical or\u0000chronic bacterial infections of the urinary tract, and hence, it is the first line choice of drug for the\u0000treatment of urinary tract infections (UTI). Although the molecule is legacy in nature, there are\u0000many challenges in terms of drug product formulation and efficacy thereof. The authors are mainly focused in this literature review on, but not limited to, understanding the molecule in terms of\u0000physico-chemical properties of the drug, pharmacokinetics and pharmacodynamics, approved and\u0000withdrawn formulations, challenges concerning drug formulation, the cause of drug shortage in\u0000the market, improvement areas in terms of formulation and its therapeutic effectiveness. The authors found during their widespread review that the major challenge in the existing conventional\u0000drug delivery system of nitrofurantoin is the fluctuation of plasma concentration owing to its variability in drug absorption. Further, they understood that the variability in absorption is due to inherent variability in particle size distribution. Based on the findings, authors also explored the\u0000possibilities to deliver the drug in novel drug delivery systems such as nano self-emulsifying\u0000emulsions, nanoemulsions and multiple emulsions where the drug can be presented in soluble\u0000form and hence the variability in absorption and fluctuation in plasma concentration of drug can\u0000be avoided and described briefly the salient features of each drug delivery in this review.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139447777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.2174/0122103031269230231213061146
Ritu Rathi, Sanshita, Inderbir Singh
In the era of pharmaceutical research and development, the most challenging aspect is to enhance the physicochemical properties of drugs. Hot Melt Extrusion (HME) is a solvent-free, one-step, continuous, scalable, and industrially feasible method for developing pharmaceutical co-crystals. Co-crystallization, as a technique, has gained significant attention for its potential to modify various physicochemical properties of drugs like solubility, stability, compressibility, permeability, taste masking, and therapeutic efficacy. We determine the characteristic features of HME and explore published literature using the keywords, HME, co-crystals, and PAT, in databases, such as PubMed, Google Scholar, ScienceDirect, and Research Gate. The present review embarks on a detailed journey through the multifaceted domain of HME and its pivotal role in co-crystal development. The process parameters, such as temperature, extruder type, screw configuration, screw speed, and feed rate, are involved in determining the characteristics of the co-crystals produced. Additionally, the review explores the role of materials, including Active Pharmaceutical Ingredients (APIs), plasticizers, polymers, and other pharmaceutical aids, underlining their impact on co-crystal development. The existing literature on HME and its application for pharmaceutical co-crystal production is comprehensively surveyed. The review highlights the utility of Process Analytical Technology (PAT) in realtime process control. The role of HME in the future of pharmaceutical co-crystal development is discussed, making this review essential for researchers and industry professionals alike.
在药物研发时代，最具挑战性的问题是如何提高药物的理化特性。热熔挤压（HME）是一种无溶剂、一步法、连续、可扩展且在工业上可行的药物共晶体开发方法。我们确定了 HME 的特征，并在 PubMed、Google Scholar、ScienceDirect 和 Research Gate 等数据库中使用 HME、共晶体和 PAT 等关键词搜索了已发表的文献。温度、挤出机类型、螺杆配置、螺杆速度和喂料速率等工艺参数决定了所生产共晶体的特性。此外，该综述还探讨了材料的作用，包括活性药物成分（API）、增塑剂、聚合物和其他制药助剂，强调了它们对共晶体开发的影响。综述强调了过程分析技术（PAT）在实时过程控制中的作用。此外，还讨论了 HME 在未来药用共晶体开发中的作用，因此本综述对研究人员和行业专业人士都非常重要。
{"title":"Hot Melt Extrusion Technique for Developing Pharmaceutical Co-crystals:\u0000A Review","authors":"Ritu Rathi, Sanshita, Inderbir Singh","doi":"10.2174/0122103031269230231213061146","DOIUrl":"https://doi.org/10.2174/0122103031269230231213061146","url":null,"abstract":"\u0000\u0000In the era of pharmaceutical research and development, the most challenging aspect is to enhance the physicochemical properties of drugs. Hot Melt Extrusion (HME)\u0000is a solvent-free, one-step, continuous, scalable, and industrially feasible method for developing\u0000pharmaceutical co-crystals. Co-crystallization, as a technique, has gained significant attention for\u0000its potential to modify various physicochemical properties of drugs like solubility, stability, compressibility, permeability, taste masking, and therapeutic efficacy.\u0000\u0000\u0000\u0000We determine the characteristic features of HME and explore published literature using\u0000the keywords, HME, co-crystals, and PAT, in databases, such as PubMed, Google Scholar, ScienceDirect, and Research Gate.\u0000\u0000\u0000\u0000The present review embarks on a detailed journey through the multifaceted domain of\u0000HME and its pivotal role in co-crystal development. The process parameters, such as temperature,\u0000extruder type, screw configuration, screw speed, and feed rate, are involved in determining the\u0000characteristics of the co-crystals produced. Additionally, the review explores the role of materials,\u0000including Active Pharmaceutical Ingredients (APIs), plasticizers, polymers, and other pharmaceutical aids, underlining their impact on co-crystal development. The existing literature on HME\u0000and its application for pharmaceutical co-crystal production is comprehensively surveyed.\u0000\u0000\u0000\u0000The review highlights the utility of Process Analytical Technology (PAT) in realtime process control. The role of HME in the future of pharmaceutical co-crystal development is\u0000discussed, making this review essential for researchers and industry professionals alike.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139001071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-05DOI: 10.2174/0122103031267809231128111259
D. A. Shaikh, Munira M. M. Momin
Ocular in situ gels (ISG) are an adequate substitute to overcome the pitfalls of conventional eye drops as they acquaintance the advantages of solutions, including accuracy, dosing frequency, and ease of administration with prolonged contact with the ocular membrane. The present investigation aims to develop the ion-triggered in situ gel (ITISG) system for the convenient administration of Ciprofloxacin HCl (CFH) and Olopatadine HCl (OLH) in combination by employing gellan gum to prolong the pre-corneal residence, optic bioavailability and declines dosing frequency. The ISG material and critical quality attributes (CQA) were identified. Quality by Design (QbD) was established to optimize the formulation. Nine experimental formulations were designed (F1-F9) and assigned to distinct physicochemical and in vitro examinations Optimized batch F2 exhibited all the findings within acceptable limits. The Ion-triggered ISG technique exhibits maximum drug release over a 240-min cycle, much more significant than conventional eyedrops (60 min), suggesting sustained drug distribution and superior corneal penetration and absorption. Comprehensive findings of the present investigation conclude that the CFH and OLH would be effectively formulated as an ion-triggered ISG system to manage several draw-backs associated with prolonged release, ocular retention, and better corneal penetration com-pared with conventional eyedrops.
{"title":"Formulation and Evaluation of Ion-Triggered In situ gel for Effective Ocular Delivery of Ciprofloxacin HCl and Olopatadine HCl in Combination","authors":"D. A. Shaikh, Munira M. M. Momin","doi":"10.2174/0122103031267809231128111259","DOIUrl":"https://doi.org/10.2174/0122103031267809231128111259","url":null,"abstract":"\u0000\u0000Ocular in situ gels (ISG) are an adequate substitute to overcome the pitfalls of conventional eye drops as they acquaintance the advantages of solutions, including accuracy, dosing frequency, and ease of administration with prolonged contact with the ocular membrane.\u0000\u0000\u0000\u0000The present investigation aims to develop the ion-triggered in situ gel (ITISG) system for the convenient administration of Ciprofloxacin HCl (CFH) and Olopatadine HCl (OLH) in combination by employing gellan gum to prolong the pre-corneal residence, optic bioavailability and declines dosing frequency.\u0000\u0000\u0000\u0000The ISG material and critical quality attributes (CQA) were identified. Quality by Design (QbD) was established to optimize the formulation. Nine experimental formulations were designed (F1-F9) and assigned to distinct physicochemical and in vitro examinations\u0000\u0000\u0000\u0000Optimized batch F2 exhibited all the findings within acceptable limits. The Ion-triggered ISG technique exhibits maximum drug release over a 240-min cycle, much more significant than conventional eyedrops (60 min), suggesting sustained drug distribution and superior corneal penetration and absorption.\u0000\u0000\u0000\u0000Comprehensive findings of the present investigation conclude that the CFH and OLH would be effectively formulated as an ion-triggered ISG system to manage several draw-backs associated with prolonged release, ocular retention, and better corneal penetration com-pared with conventional eyedrops.\u0000","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138598199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-24DOI: 10.2174/0122103031255282231117053143
José Puertas, Arianne López, Francisco González Cazorla, Manuel Giménez Labrador, Mattias Adrian Repetto Baubin, Manuel José Lis Arias
For some medical treatments associated with cancer, the invasion of organs is required, which must be done in a totally controlled way to obtain the expected results in the treatment. Today, most medical treatments make use of invasive therapies to combat the affected cancer tissues. Acting in this way also destroys those tissues not affected by the generation of tumor centers that confront the cancer tumor center to be treated. To ensure the objective of the treatment, doses of the drug to be administered in a little controlled and free via are used that are ultimately ineffective due to the high degradation of the active compound due to its non-existent stabilization and protection after its passage through the body and consequently possible episodes of phagocytization, responsible for the reticuloendothelial system. It is well known the side effects that one of the most promising anti-cancer molecules, doxorubicin, shows. This is a problem for its use, and one of the possibilities to avoid these desired behaviors, microencapsulation could be a possible approach. Microencapsulation of drugs allows the design of micro-level structures capable of containing the active agent with sufficient protection and stabilization to be able to reach the target site with the highest possible concentration of drug to be able to be gradually released in its entirety and produce the desired effect in the therapy in a controlled way according to a previously studied kinetic profile, which will allow a type of treatment in which the therapy will be noninvasive due to the high degree of targeting selectivity that the microcapsule allows. The use of the amine groups present in the chitosan polymer's structure to increase or modify the molecular interactions with doxorubicin is a very interesting aspect that will be treated here. These interactions help to make possible the control and protection of the active principle, as it is shown in the quantification of the drug-delivery behavior of the system made.
{"title":"Microencapsulation of Doxorubicin using Chitosan","authors":"José Puertas, Arianne López, Francisco González Cazorla, Manuel Giménez Labrador, Mattias Adrian Repetto Baubin, Manuel José Lis Arias","doi":"10.2174/0122103031255282231117053143","DOIUrl":"https://doi.org/10.2174/0122103031255282231117053143","url":null,"abstract":"For some medical treatments associated with cancer, the invasion of organs is required, which must be done in a totally controlled way to obtain the expected results in the treatment. Today, most medical treatments make use of invasive therapies to combat the affected cancer tissues. Acting in this way also destroys those tissues not affected by the generation of tumor centers that confront the cancer tumor center to be treated. To ensure the objective of the treatment, doses of the drug to be administered in a little controlled and free via are used that are ultimately ineffective due to the high degradation of the active compound due to its non-existent stabilization and protection after its passage through the body and consequently possible episodes of phagocytization, responsible for the reticuloendothelial system. It is well known the side effects that one of the most promising anti-cancer molecules, doxorubicin, shows. This is a problem for its use, and one of the possibilities to avoid these desired behaviors, microencapsulation could be a possible approach. Microencapsulation of drugs allows the design of micro-level structures capable of containing the active agent with sufficient protection and stabilization to be able to reach the target site with the highest possible concentration of drug to be able to be gradually released in its entirety and produce the desired effect in the therapy in a controlled way according to a previously studied kinetic profile, which will allow a type of treatment in which the therapy will be noninvasive due to the high degree of targeting selectivity that the microcapsule allows. The use of the amine groups present in the chitosan polymer's structure to increase or modify the molecular interactions with doxorubicin is a very interesting aspect that will be treated here. These interactions help to make possible the control and protection of the active principle, as it is shown in the quantification of the drug-delivery behavior of the system made.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139242114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-16DOI: 10.2174/0122103031270911231106114419
Aruna Rawat, V. Jhawat, Samrat Chauhan, Rohit Dutt
This study aimed to evaluate the therapeutic efficacy of telmisartan-loaded novel curcumin-tagged solid nanodispersion in streptozotocin-nicotinamide-induced diabetic nephropathy in Wistar rats The objective of this study was to perform a comprehensive pharmacokinetic and pharmacodynamic evaluation of a novel curcumin-tagged solid nanodispersion loaded with telmisartan, with the aim of assessing its potential as a treatment for diabetic nephropathy in an animal model. Specifically, the following objectives will be addressed: formulation and characterization, in vitro evaluation, pharmacokinetics and pharmacodynamics evaluation, and comparative analysis. Telmisartan-loaded curcumin-tagged solid nanodispersion was prepared using the emulsion solvent evaporation method. The optimized formulation was evaluated for pharmacokinetic and pharmacodynamic parameters in an animal model. Wistar rats were divided into 5 groups, with 6 animals in each group. Diabetes was induced using nicotinamide (240 mg/kg) and streptozotocin (55 mg/kg, i.p.) injections in the animals. After 30 to 45 days of introduction, diabetic nephropathy was manifested. The kidneys and pancreas were used for histological analysis and renal and pancreatic damage assessment. In-vivo studies showed better bioavailability with the t1/2 and Cmax of TLS-15 was 14.92 ± 0.47 hours and 0.32 ± 0.009, respectively, within 2 hours as compared to the t1/2 and Cmax of MP was 4.38 ± 0.19 hours and 0.19 ± 0.008 owing to the better dissolution due to solubility improvement. When compared to the commercially available product, TLS-15 was found to have blood glucose and body weight that were, respectively, 1.01 and 1.03 times higher. Kidney measures, such as serum urea and creatinine, were found to be 0.71 and 1.16 times lower for TLS-15, respectively, and albumin had a value that was 1.13 times higher than for the commercial formulation. Urine indicators, urine albumin, and creatinine estimations, as well as cytokine estimations, revealed that TLS-15 had creatinine levels that were 1.17 times higher and IL-6 levels that were 0.77 times higher than those of a commercial batch. The findings strongly support the renoprotective and pancreatic protective effects of TLS and Cur (SND-Solid Nanodispersion) combined by lowering levels of cytokines factor (IL6), kidney, and lipid parameters. The postulated mechanism might be the combined inhibitory action of TLS and Cur.
{"title":"Pharmacokinetic and Pharmacodynamic Evaluation of Telmisartanloaded Novel Curcumin-tagged Solid Nanodispersion for the Treatment of Diabetic Nephropathy in an Animal Model","authors":"Aruna Rawat, V. Jhawat, Samrat Chauhan, Rohit Dutt","doi":"10.2174/0122103031270911231106114419","DOIUrl":"https://doi.org/10.2174/0122103031270911231106114419","url":null,"abstract":"This study aimed to evaluate the therapeutic efficacy of telmisartan-loaded novel curcumin-tagged solid nanodispersion in streptozotocin-nicotinamide-induced diabetic nephropathy in Wistar rats The objective of this study was to perform a comprehensive pharmacokinetic and pharmacodynamic evaluation of a novel curcumin-tagged solid nanodispersion loaded with telmisartan, with the aim of assessing its potential as a treatment for diabetic nephropathy in an animal model. Specifically, the following objectives will be addressed: formulation and characterization, in vitro evaluation, pharmacokinetics and pharmacodynamics evaluation, and comparative analysis. Telmisartan-loaded curcumin-tagged solid nanodispersion was prepared using the emulsion solvent evaporation method. The optimized formulation was evaluated for pharmacokinetic and pharmacodynamic parameters in an animal model. Wistar rats were divided into 5 groups, with 6 animals in each group. Diabetes was induced using nicotinamide (240 mg/kg) and streptozotocin (55 mg/kg, i.p.) injections in the animals. After 30 to 45 days of introduction, diabetic nephropathy was manifested. The kidneys and pancreas were used for histological analysis and renal and pancreatic damage assessment. In-vivo studies showed better bioavailability with the t1/2 and Cmax of TLS-15 was 14.92 ± 0.47 hours and 0.32 ± 0.009, respectively, within 2 hours as compared to the t1/2 and Cmax of MP was 4.38 ± 0.19 hours and 0.19 ± 0.008 owing to the better dissolution due to solubility improvement. When compared to the commercially available product, TLS-15 was found to have blood glucose and body weight that were, respectively, 1.01 and 1.03 times higher. Kidney measures, such as serum urea and creatinine, were found to be 0.71 and 1.16 times lower for TLS-15, respectively, and albumin had a value that was 1.13 times higher than for the commercial formulation. Urine indicators, urine albumin, and creatinine estimations, as well as cytokine estimations, revealed that TLS-15 had creatinine levels that were 1.17 times higher and IL-6 levels that were 0.77 times higher than those of a commercial batch. The findings strongly support the renoprotective and pancreatic protective effects of TLS and Cur (SND-Solid Nanodispersion) combined by lowering levels of cytokines factor (IL6), kidney, and lipid parameters. The postulated mechanism might be the combined inhibitory action of TLS and Cur.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139267244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-25DOI: 10.2174/0122103031253788231020060301
A. Schönthal, Julio Thome, Daniela Carneiro de Lima, Thomas C. Chen, Clovis O. da Fonseca
Perillyl alcohol (POH) is a naturally occurring monoterpene that is being developed as an intranasally delivered agent for the treatment of brain-localized malignancies. Clinical trials with glioma patients in Brazil have yielded preliminary evidence that this approach might be able to achieve therapeutic activity and result in prolonged survival of patients. NEO100, a highly pure, current good manufacturing practice-produced version of POH, is being evaluated in a Phase I/IIa clinical trial with recurrent glioblastoma patients in the United States. Patients self-administer POH/NEO100 as a mist with a nasal mask over the course of 15 minutes, four times a day, every day. The treatment regimen is well tolerated, even if maintained over several years. It correlated with improved survival when compared to historical controls. There is a possibility that this novel approach could become useful for the treatment of malignant glioma.
{"title":"Intranasal Delivery of Perillyl Alcohol (NEO100) as a New Treatment Strategy for Glioma","authors":"A. Schönthal, Julio Thome, Daniela Carneiro de Lima, Thomas C. Chen, Clovis O. da Fonseca","doi":"10.2174/0122103031253788231020060301","DOIUrl":"https://doi.org/10.2174/0122103031253788231020060301","url":null,"abstract":"Perillyl alcohol (POH) is a naturally occurring monoterpene that is being developed as an intranasally delivered agent for the treatment of brain-localized malignancies. Clinical trials with glioma patients in Brazil have yielded preliminary evidence that this approach might be able to achieve therapeutic activity and result in prolonged survival of patients. NEO100, a highly pure, current good manufacturing practice-produced version of POH, is being evaluated in a Phase I/IIa clinical trial with recurrent glioblastoma patients in the United States. Patients self-administer POH/NEO100 as a mist with a nasal mask over the course of 15 minutes, four times a day, every day. The treatment regimen is well tolerated, even if maintained over several years. It correlated with improved survival when compared to historical controls. There is a possibility that this novel approach could become useful for the treatment of malignant glioma.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139313885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acne vulgaris is an inflammatory disorder of the skin that occurs when hair follicles get clogged with sebum and dead skin cells resulting in pustules, papules, or nodules. This condi-tion affects a large number of people throughout the world. Over time, various conventional ther-apies like topical, systemic and hormonal treatments have been prescribed by doctors to patients for managing acne. Amongst these, topical therapy is the first-line therapy dominated by retinoid and antibiotic drugs. However, conventional topical treatments have many drawbacks concerning physicochemical instability, poor ability to penetrate the skin, and wide-ranging side effects. Novel drug delivery systems are the formulations that were first devised to overcome the issues faced by traditional methods. Researchers have developed novel therapies for topical use, such as niosomes, transfersomes, solid lipid nanoparticles, microsponges, microemulsion, microspheres, nanocochleates, and liposomes, which can be used to target acne. These nanoparticulate systems aim to overcome the disadvantages of conventional treatment and provide higher safety and effi-cacy, along with an increase in the stability of the formulation. Many comparative studies have been conducted between the novel and conventional methods, which give us a better understand-ing of the safety and efficacy of drugs present in the formulation and prove that novel drug deliv-ery systems are more favorable than their conventional counterparts. This review article provides a brief insight into the conventional methods, discusses in depth the earlier mentioned novel ther-apies that can be used successfully in treating acne, and provides patent information on the drug delivery systems.
{"title":"Recent Advances in Combating Acne with Novel Drug Delivery Systems: A Review","authors":"Melroy D'Sa, Shreyash Mahadik, Nrupesh Patel, Sahaya Nadar","doi":"10.2174/0122103031246178231001111944","DOIUrl":"https://doi.org/10.2174/0122103031246178231001111944","url":null,"abstract":"Acne vulgaris is an inflammatory disorder of the skin that occurs when hair follicles get clogged with sebum and dead skin cells resulting in pustules, papules, or nodules. This condi-tion affects a large number of people throughout the world. Over time, various conventional ther-apies like topical, systemic and hormonal treatments have been prescribed by doctors to patients for managing acne. Amongst these, topical therapy is the first-line therapy dominated by retinoid and antibiotic drugs. However, conventional topical treatments have many drawbacks concerning physicochemical instability, poor ability to penetrate the skin, and wide-ranging side effects. Novel drug delivery systems are the formulations that were first devised to overcome the issues faced by traditional methods. Researchers have developed novel therapies for topical use, such as niosomes, transfersomes, solid lipid nanoparticles, microsponges, microemulsion, microspheres, nanocochleates, and liposomes, which can be used to target acne. These nanoparticulate systems aim to overcome the disadvantages of conventional treatment and provide higher safety and effi-cacy, along with an increase in the stability of the formulation. Many comparative studies have been conducted between the novel and conventional methods, which give us a better understand-ing of the safety and efficacy of drugs present in the formulation and prove that novel drug deliv-ery systems are more favorable than their conventional counterparts. This review article provides a brief insight into the conventional methods, discusses in depth the earlier mentioned novel ther-apies that can be used successfully in treating acne, and provides patent information on the drug delivery systems.","PeriodicalId":11310,"journal":{"name":"Drug Delivery Letters","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135198604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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