Abstract:
:New biopharmaceutical molecules, potentially able to provide more personalized and effective treatments, are being identified through the advent of advanced synthetic biology strategies, sophisticated chemical synthesis approaches, and new analytical methods to assess biological potency. However, translation of many of these structures has been significantly limited due to the need for more efficient strategies to deliver macromolecular therapeutics to desirable intracellular sites of action. Engineered nanocarriers that encapsulate peptides, proteins, or nucleic acids are generally internalized into target cells via one of several endocytic pathways. These nanostructures, entrapped within endosomes, must navigate the intracellular milieu to orchestrate delivery to the intended destination, typically the cytoplasm or nucleus. For therapeutics active in the cytoplasm, endosomal escape continues to represent a limiting step to effective treatment, since a majority of nanocarriers trapped within endosomes are ultimately marked for enzymatic degradation in lysosomes. Therapeutics active in the nucleus have the added challenges of reaching and penetrating the nuclear envelope, and nuclear delivery remains a preeminent challenge preventing clinical translation of gene therapy applications. Herein, we review cutting-edge peptide- and polymer-based design strategies with the potential to enable significant improvements in biopharmaceutical efficacy through improved intracellular targeting. These strategies often mimic the activities of pathogens, which have developed innate and highly effective mechanisms to penetrate plasma membranes and enter the nucleus of host cells. Understanding these mechanisms has enabled advances in synthetic peptide and polymer design that may ultimately improve intracellular trafficking and bioavailability, leading to increased access to new classes of biotherapeutics.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Munsell EV,Ross NL,Sullivan MOdoi
10.2174/1381612822666151216151420subject
Has Abstractpub_date
2016-01-01 00:00:00pages
1227-44issue
9eissn
1381-6128issn
1873-4286pii
CPD-EPUB-72551journal_volume
22pub_type
杂志文章,评审abstract::The maintenance and regulation of cellular NAD(P)(H) content and its influence on cell function involves many metabolic pathways, some of which remain poorly understood. Niacin deficiency in humans, which leads to low NAD status, causes sun sensitivity in skin, indicative of deficiencies in responding to UV damage. An...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787185760
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:The emerging evidence has recently shown an evident dependence between recently identified salusin peptides and atherosclerosis, and their important roles as endogenous modulators of atherogenesis. It was reported that the development of atherosclerosis could also be affected by endogenous salusin- β overproduc...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666180607124531
更新日期:2018-01-01 00:00:00
abstract::Androgen receptor (AR) is a steroid hormone receptor that is activated by endogenous androgens, mainly testosterone and 5alpha-dihydrotestosterone (5alpha-DHT). AR is also an important drug target, and AR antagonists (antiandrogens) have been widely used for prostate cancer therapy. Antiandrogens currently available o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790963850
更新日期:2010-01-01 00:00:00
abstract::The acidic amino acid L-glutamate acts as both a primary excitatory neurotransmitter and a potential neurotoxin within the mammalian central nervous system. Functionally juxtaposed between these neurophysiological and pathological actions are an assorted group of integral membrane transporter proteins that rapidly and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-05-01 00:00:00
abstract::Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and RNA polymerase II transcription. Several pharmacological CDK inhibitors (PCIs) are currently in clinical trials as potential cancer therapeutics since CDK hyperactivation is detected in the majority of neoplasias. Within the last few years, the a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777442083
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:High prevalence of Dental and periodontal problems during the gestation period may have a negative effect on oral health-related quality of life (OHRQoL) in pregnant women. This systematic review aimed to perform a quality assessment and provide a critical overview of the current research available on OHRQoL ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200523171639
更新日期:2020-01-01 00:00:00
abstract::Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200730220230
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Lipid nanoparticles have attracted increased degree of scientific and commercial attention in the last decade. The lipidic nanoparticles have emerged as a potential alternative to other nano-scale systems due to their various advantages over them and also due to overcoming the shortcomings of the already ava...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612823666171122104216
更新日期:2017-11-21 00:00:00
abstract::The vasoconstrictive and antidiuretic physiologic properties of vasopressin (antidiuretic hormone) have long been known. Until recently however, vasopressin was mostly used for diabetes insipidus and noctournal enuresis. This review summarizes the growing body of evidence regarding the perioperative use of vasopressin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803832326
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The use of aromatic plants to relief different illness is not a new therapy. Actually aromatic plants have been used for many centuries by different cultures around the world. Pharmacological studies provide scientific support to the traditional use of aromatic medicinal plants and aromatherapy; nevertheless...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160607065917
更新日期:2016-01-01 00:00:00
abstract::The prevalence of obesity is increasing globally. Rational perioperative anesthetic drug selection and administration require knowledge of how obesity interacts with those drugs. In this review, we summarize different aspects of the anesthetic agents, including pharmacokinetics (PK), pharmacodynamics (PD) and clinical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190628161206
更新日期:2019-01-01 00:00:00
abstract::In order to develop an effective pharmacological treatment for obesity, an endogenous factor that promotes a positive energy balance by increasing appetite and decreasing fat oxidation could represent the drug target scientists have been looking for. The recently discovered gastric endocrine agent ghrelin, which appea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454748
更新日期:2003-01-01 00:00:00
abstract::Toll-like receptors (TLRs) have emerged as critical players in immunity. They are capable of sensing organisms ranging from protozoa to bacteria, fungi or viruses upon detection of the pathogen as well as recognizing endogenous ligands, and triggering transduction pathways. Following activation of the innate immune sy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778743493
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:In the last decade, the development of anti-inflammatory strategies emerged as new trend in cardiovascular (CV) pharmacotherapy. Anti-inflammatory properties have been previously identified in different classes of drugs used in primary CV prevention. However, the extent to which the modification of inflammat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160822124546
更新日期:2016-01-01 00:00:00
abstract::Immune activation not only accompanies inflammation in various disorders including infections, autoimmune syndromes and cancer, but it also represents a characteristic feature of ageing. Immune deviations which are most widely expressed in the elderly include increased neopterin production and tryptophan breakdown. Th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140317110217
更新日期:2014-01-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease worldwide. This is primarily driven by the global epidemic of obesity and diabetes as well as the aging of the general population. Most of the epidemiology data of NAFLD for North America are published from stud...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200303114934
更新日期:2020-01-01 00:00:00
abstract::Sulphur mustard (SM; (2, 2'-dichloroethylsulfide)) was used for the first time in 1917, during the World War I. SM mainly induces DNA damage, oxidative stress, and inflammation. This compound injures the respiratory system, eyes, skin and the endocrine, gastrointestinal, and hematopoietic systems. However, due to the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180903112218
更新日期:2018-01-01 00:00:00
abstract::Lysine acetylation plays an essential role in metabolism. Five individual studies have identified that a large number of cellular proteins are potentially acetylated. Notably, almost every enzyme involved in central metabolic pathways such as glycolysis, the TCA cycle, fat acid metabolism, urea cycle and glycogen meta...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990487
更新日期:2014-01-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel member of the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily. In vertebrates, including avians, it occurs in two forms: PACAP(38) and PACAP(27). PACAP structure is well conserved during evolution, being identical in mammals, and s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033391586
更新日期:2003-01-01 00:00:00
abstract::Kv7.x channels are a family of six transmembrane domain, single pore-loop, voltage-gated K(+) channels. Five members of the family have been identified to date, including the cardiac channel Kv7.1 (formerly known as KvLQT1) and four neuronal Kv7.x channels, Kv7.2-5. Heteromeric channels containing Kv7.3 and either Kv7...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788186326
更新日期:2009-01-01 00:00:00
abstract::With a 2030 projection of 23.6 million deaths per year the prevalence and severity of cardiovascular disease is at an astounding high. Thus, a definitive need for the identification of novel compounds with potential to prevent or treat the disease and associated states. Moreover, there is also an ever-increasing need ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200909125354
更新日期:2020-09-09 00:00:00
abstract::Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. Inflammation plays a key role in AD and dissecting the genetics of inflammation may provide an answer to the possible treatment. Hence, the better understanding of diffe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161208786264089
更新日期:2008-01-01 00:00:00
abstract::Nucleoside reverse transcriptase inhibitors (NRTIs) are components of most current antiretroviral (ARV) regimens. Side effects arising from mitochondrial toxicity (MtT) induced by these drugs is a common reason why patients treated with NRTI change or discontinue therapy. These toxicities can be difficult to reverse, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793563482
更新日期:2010-10-01 00:00:00
abstract::The mechanisms underlying neurodegeneration in amyotrophic lateral sclerosis (ALS) are multifactorial and include genetic and environmental factors. Nowadays, it is well accepted that neuronal loss is driven by non-cell autonomous toxicity. Non-neuronal cells, such as astrocytes, have been described to significantly c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170615110856
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:From the evidence of failed injection-based growth factor therapies, it has been proposed that a naturally triggered uninterrupted blood circulation of the growth factors would be superior. OBJECTIVE:We seek to stimulate discussions and more research about the possibility of using the already available grow...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201019104201
更新日期:2020-10-18 00:00:00
abstract::Advances in particle engineering techniques, such as spray drying, freeze drying and supercritical fluid precipitation, have greatly enhanced the ability to control the structure, morphology, and solid state phase of inhalable sized particles (1 - 5 µm) for formulation in pressurized metered dose inhalers (pMDI). To o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150820110153
更新日期:2015-01-01 00:00:00
abstract::The apoptosis inducing factor (AIF) was first discovered as a caspase-independent apoptosis effector that promoted cell death upon release from the mitochondria (triggered by pro-apoptotic stimuli) and relocalization into the nucleus, where it promotes chromatin condensation and DNA fragmentation. AIF is a mammalian m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319140012
更新日期:2013-01-01 00:00:00
abstract::Emerging evidence has shown that microRNAs (miRNAs) can act as oncogenes in the initiation and progression of leukemia and lymphoma. Aberrant expression of oncogenic miRNAs, including miR-155, miR-17-92, miR-21, miR-125b, miR-93, miR-143-p3, miR-196b, and miR-223 promotes leukemogenesis through increasing the leukemic...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140128211724
更新日期:2014-01-01 00:00:00
abstract::Natural products, or their synthetic derivatives are a treasure trove to find potential candidates for novel drugs for human treatment. The selection of diamonds from the huge pile of worthless stone is a critical--and difficult--stage in the discovery pipeline. Of all the factors to be considered, perhaps the most im...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151002114227
更新日期:2015-01-01 00:00:00
abstract::Synaptic transmission through descending motor pathways to lumbar motoneurons and then to leg muscles is essential for walking in humans and rats. Spinal cord injury (SCI), even when incomplete, results in diminished transmission to motoneurons and very limited recovery of motor function. Neurotrophins have emerged as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990378
更新日期:2013-01-01 00:00:00