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PeerJ 2015Current ovarian cancer treatment involves chemotherapy that has serious limitations, such as rapid clearance, unfavorable biodistribution and severe side effects. To...
Current ovarian cancer treatment involves chemotherapy that has serious limitations, such as rapid clearance, unfavorable biodistribution and severe side effects. To overcome these limitations, drug delivery systems (DDS) have been developed to encapsulate chemotherapeutics for delivery to tumor cells. However, no systematic assessment of the efficacy of chemotherapy by DDS compared to free chemotherapy (not in a DDS) has been performed for animal studies. Here, we assess the efficacy of chemotherapy in DDS on survival and tumor growth inhibition in animal studies. We searched PubMed and EMBASE (via OvidSP) to systematically identify studies evaluating chemotherapeutics encapsulated in DDS for ovarian cancer treatment in animal studies. Studies were assessed for quality and risk of bias. Study characteristics were collected and outcome data (survival/hazard ratio or tumor growth inhibition) were extracted and used for meta-analyses. Meta-analysis was performed to identify and explore which characteristics of DDS influenced treatment efficacy. A total of 44 studies were included after thorough literature screening (2,735 studies found after initial search). The risk of bias was difficult to assess, mainly because of incomplete reporting. A total of 17 studies (377 animals) and 16 studies (259 animals) could be included in the meta-analysis for survival and tumor growth inhibition, respectively. In the majority of the included studies chemotherapeutics entrapped in a DDS significantly improved efficacy over free chemotherapeutics regarding both survival and tumor growth inhibition. Subgroup analyses, however, revealed that cisplatin entrapped in a DDS did not result in additional tumor growth inhibition compared to free cisplatin, although it did result in improved survival. Micelles did not show a significant tumor growth inhibition compared to free chemotherapeutics, which indicates that micelles may not be a suitable DDS for ovarian cancer treatment. Other subgroup analyses, such as targeted versus non-targeted DDS or IV versus IP administration route, did not identify specific characteristics of DDS that affected treatment efficacy. This systematic review shows the potential, but also the limitations of chemotherapy by drug delivery systems for ovarian cancer treatment. For future animal research, we emphasize that data need to be reported with ample attention to detailed reporting.
PubMed: 26713240
DOI: 10.7717/peerj.1489 -
Journal of Controlled Release :... Jan 2018The treatment of neurodegenerative and psychiatric disorders remains a challenge in medical research. Several strategies have been developed over the years, either to...
The treatment of neurodegenerative and psychiatric disorders remains a challenge in medical research. Several strategies have been developed over the years, either to overcome the blood-brain barrier or to achieve a safer or faster brain delivery, one of them being intranasal (IN) administration. The possibility of direct nose-to-brain transport offers enhanced targeting and reduced systemic side effects. Nevertheless, labile, low soluble, low permeant and/or less potent drugs might need a formulation other than the common solutions or suspensions. For that, the formulation of nanosystems is considered to be a promising approach, since it can protect drugs from chemical and/or metabolic degradation, enhance their solubility, or offer transport through biological membranes. However, the understanding of the factors promoting efficient brain targeting when using nanosystems through the nasal route is currently patchy and incomplete. The main purpose of the present review was to evaluate the association between brain delivery efficacy (in terms of brain targeting, brain bioavailability and time to reach the brain) and nanosystem type. For that, we performed a systematic bibliographic search and analysis. Furthermore, study designs, nanosystem properties, and reporting quality were also analyzed and discussed. It was found a high heterogeneity in how pre-clinical brain targeting studies have been conducted, analyzed and reported in scientific literature, which surely originates a significant degree of bias and data dispersion. This review attempts to provide some systematization recommendations, which may be useful for researchers entering the field, and assist in increasing the uniformity of future reports. The analysis of literature data confirmed that there is evidence of the advantage of the IN route (when compared to the intravenous route) and in using carrier nanosystems (when compared to IN solutions) for brain delivery of a large set of drugs. Among the most represented nanosystem classes, microemulsions had some of the lowest pharmacokinetic ratios values, while polymeric micelles had some of the best. Nevertheless, brain targeting efficacy comparisons between nanosystem groups had little statistical significance, and the superiority of the polymeric micelles group disappeared when nanosystems were compared to the respective IN drug solutions. In fact, some drugs reached the brain so efficiently, even as drug solutions, that further benefit from formulating them into nanosystems became less evident.
Topics: Administration, Intranasal; Animals; Biological Transport; Brain; Drug Delivery Systems; Humans; Nanostructures; Nasal Mucosa
PubMed: 29199063
DOI: 10.1016/j.jconrel.2017.11.047 -
Iranian Journal of Pharmaceutical... 2021Polymeric micelles (PMs) are one of Nanoscale delivery systems with high stability, loading capacity, and biocompatibility. PMs are nano-sized and spherical particles... (Review)
Review
Polymeric micelles (PMs) are one of Nanoscale delivery systems with high stability, loading capacity, and biocompatibility. PMs are nano-sized and spherical particles with a hydrophilic shell and hydrophobic core or reverse depending on their applications. Polymeric micelles could be synthesized by different methods, such as direct dissolution, dialysis method, and lyophilization. Microfluidics is also a relatively modern approach for this purpose, in which chemical reactions are carried out in the microchannels. Compared with conventional preparation methods, the microfluidic technique produces homogeneous polymeric micelles with desirable features, tunable particle size, and relatively high drug loading. These advantages are originated from the ability of microfluidics in precise control over the streamlines of reactants without chaotic turbulence. Although the synthesis of polymeric micelles by the microfluidic platform is advantageous, little or no review has been conducted to provide a clear image of the different PMs preparation by the microfluidic approach. Thus, in this review, the production of the PMs, utilizing microfluidic procedures to enhance their favorable characteristics is investigated. For this purpose, an electronic search is conducted on PubMed, Web of Science, Scopus, and Embase databases for retrieval of relevant papers. Seven papers are included in this systematic review. Preparation of PMs by the microfluidic approach and the effect of different parameters, such as the flow rate ratio, channel dimensions, drug concentration, and organic solvent type on PMs characteristics is obtained from the included papers.
PubMed: 34567158
DOI: 10.22037/ijpr.2021.114226.14769 -
Advanced Drug Delivery Reviews 2020Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain...
Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.
Topics: Animals; Biological Transport; Blood-Brain Barrier; Cerebral Ventricles; Cerebrospinal Fluid; Drug Delivery Systems; Humans; Injections, Spinal; Liposomes; Micelles; Nanoparticles; Subarachnoid Space
PubMed: 32142739
DOI: 10.1016/j.addr.2020.02.006 -
Frontiers in Pharmacology 2022Although numerous nanoparticle formulations have been developed for ocular administration, concerns are being raised about a possible mismatch between potential...
Although numerous nanoparticle formulations have been developed for ocular administration, concerns are being raised about a possible mismatch between potential promises made by the field of nanoparticle research and demonstration of actual therapeutic benefit. Therefore, the primary focus of this present review was to critically assess to what extent nanoencapsulation of ocular drugs improved the therapeutic outcome when treating conditions in the anterior segment of the eye. A systematic search was conducted using Medline, PubMed, and Embase databases as well as Google Scholar for published peer-reviewed articles in English focusing on conventional nanoparticles used as drug delivery systems to the anterior segment of the eye in studies. The major therapeutic outcomes were intraocular pressure, tear secretion, number of polymorphonuclear leucocytes and pupil size. The outcome after encapsulation was compared to the non-encapsulated drug. From the search, 250 results were retrieved. Thirty-eight studies met the inclusion criteria. Rabbits were used as study subjects in all but one study, and the number of animals ranged from 3 to 10. Coated and uncoated liposomes, lipid-based and polymeric nanoparticles, as well as micelles, were studied, varying in both particle size and surface charge, and encapsulating a total of 24 different drugs, including 6 salts. The majority of the studies demonstrated some improvement after nanoencapsulation, but the duration of the benefit varied from less than 1 h to more than 20 h. The most common methods performed in the studies were drug release, transcorneal permeation, and mucin interaction. Nanoparticles that are small and mucoadhesive, often due to positive surface charge, appeared beneficial. Although assays can unravel more of the hidden and sophisticated interplay between the encapsulated drug and the nanoparticle structure, they suffered from a lack of - correlation. Therefore, more research should be focused towards developing predictive models, allowing rational design and systematic optimization of ocular nanoparticles with minimal animal experimentation.
PubMed: 35645827
DOI: 10.3389/fphar.2022.903519 -
Current Drug Delivery Apr 2023Melanoma is a malignant skin cancer type with a high lethality rate due to active metastasis. Among the risk factors for its development is exposure to ultraviolet...
BACKGROUND
Melanoma is a malignant skin cancer type with a high lethality rate due to active metastasis. Among the risk factors for its development is exposure to ultraviolet radiation (UV) and phenotypical characteristics such as clear skin and eyes. Given the difficulties of the conventional therapy, the high cost of the treatment and the low bioavailability of drugs, it is important to develop new therapeutic methods to circumvent this situation. Nanosystems such as micelles, liposomes and nanoparticles present advantages when compared to conventional treatments.
OBJECTIVE
The objective of this paper is to carry out a literature review based on articles that dealt with the use of siRNA-loaded nanosystems for the treatment of melanoma, with trials carried out in vivo to assess tumor size.
METHODS
The search was conducted in the Web of Science and PubMed databases considering the last 5 years, that is, the period between January 2017 to December 2021. The "SiRNA and Drug Delivery Systems and Melanoma" keywords were used in both databases, and the articles were analyzed using the inclusion and exclusion criteria established for this paper.
RESULTS
The results obtained indicated that using siRNA transported via nanosystems was capable of silencing the BRAF tumor genes and of reducing tumor size and weight, not presenting in vitro and/or in vivo toxicity.
CONCLUSION
Such being the case, the development of these systems becomes a non-invasive and promising option for the treatment of melanoma.
PubMed: 37170995
DOI: 10.2174/1567201820666230425234700