Unveiling the clinical and proteomic spectrum of relapsing polychondritis with respiratory involvement.
Authors: Fang X, Liao X, Gao W, Pei W, Xu W, Wang Y, Wu Y, Chen R, Ding J, Wang M, Zhu X, Zhang H, Ren DN, Li Q, Gao S
Journal: Frontiers in immunology
depression treatment
mental health
open access
Abstract
Hypertension is the leading
modifiable risk factor for global morbidity
and mortality, accounting for about 29% of cardiovascular deaths,
and is expected to affect nearly 33% of the population by 2025 due
to increasing obesity and aging. It is defined as a systolic blood
pressure higher than 140 mmHg or a diastolic blood pressure higher
than 90 mmHg, and occurs either as secondary hypertension or, more
commonly (90%), as essential hypertension. As
a chronic condition, it requires long-term pharmacological treatment. Using oral drugs is a comfortable way to treat diseases that require
long-term treatment, such as hypertension. In addition, the oral route
is a more preferred method of drug administration because of its patient-friendliness,
safety, cost-effectiveness, flexibility in dosage adjustment, and
suitability for long-term use. Oral therapy for hypertension
commonly employs representatives of multiple pharmacologic categories:
thiazide-based diuretics, β-adrenoceptor antagonists, angiotensin-converting
enzyme inhibitors, angiotensin II receptor antagonists, and L-type
calcium-channel antagonists. According
to the ESC/ESH guidelines, β-blockers are a group included in
the first-line treatment in hypertension patients with certain indications. β-adrenergic receptor antagonists,
commonly known as β-blockers,
are widely prescribed for hypertension, arrhythmias, and coronary
heart disease. Nadolol (NDL), (2,3)-5-[3-(-butylamino)-2-hydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol,
is an active ingredient in the group of nonselective β-blockers. In addition to the treatment of hypertension,
it is used in the clinic to prevent angina pectoris and esophageal varices, to treat hereditary or familial
essential tremor disease, and to reduce peripheral physiological symptoms
of anxiety and migraine prophylaxis. NDL is present in conventional tablet preparation
used orally in the market. Its bioavailability is around 30%. In oral drug design, exposure to different conditions
of the gastrointestinal tract such as pH change from acidic to basic,
various enzymes and surfactants (such as lipases, pepsinogens, pepsins,
bile, etc.), gastrointestinal microbiota, mucus barrier, and epithelial
layer results in low bioavailability. Nadolol (NDL)
is classified as a Biopharmaceutics Classification System (BCS) Class
III drug, characterized by high solubility but low intestinal permeability.
This limited permeability represents a major barrier to oral bioavailability.
The lipophilicity of NDL, expressed as its partition coefficient (log
P), has been reported to be relatively low, supporting its poor membrane
permeability behavior. Therefore, formulation strategies that can
enhance intestinal permeability are of particular interest. In order to overcome these challenging conditions, there is a need
for a new generation of oral drug delivery systems such as microcapsules,
microspheres, microsponges, nanoparticles, polymeric micelles, dendrimers,
carbon nanotubes, solid lipid nanoparticles, liposomes, and microemulsions with a lower side effect profile and more effectiveness. While studies specifically exploring microemulsion-based
formulations of nadolol are limited, evidence from other drugs suggests
that microemulsion systems can improve intestinal uptake and pharmacokinetic
profiles by enhancing membrane transport and lymphatic uptake.
modifiable risk factor for global morbidity
and mortality, accounting for about 29% of cardiovascular deaths,
and is expected to affect nearly 33% of the population by 2025 due
to increasing obesity and aging. It is defined as a systolic blood
pressure higher than 140 mmHg or a diastolic blood pressure higher
than 90 mmHg, and occurs either as secondary hypertension or, more
commonly (90%), as essential hypertension. As
a chronic condition, it requires long-term pharmacological treatment. Using oral drugs is a comfortable way to treat diseases that require
long-term treatment, such as hypertension. In addition, the oral route
is a more preferred method of drug administration because of its patient-friendliness,
safety, cost-effectiveness, flexibility in dosage adjustment, and
suitability for long-term use. Oral therapy for hypertension
commonly employs representatives of multiple pharmacologic categories:
thiazide-based diuretics, β-adrenoceptor antagonists, angiotensin-converting
enzyme inhibitors, angiotensin II receptor antagonists, and L-type
calcium-channel antagonists. According
to the ESC/ESH guidelines, β-blockers are a group included in
the first-line treatment in hypertension patients with certain indications. β-adrenergic receptor antagonists,
commonly known as β-blockers,
are widely prescribed for hypertension, arrhythmias, and coronary
heart disease. Nadolol (NDL), (2,3)-5-[3-(-butylamino)-2-hydroxypropoxy]-1,2,3,4-tetrahydronaphthalene-2,3-diol,
is an active ingredient in the group of nonselective β-blockers. In addition to the treatment of hypertension,
it is used in the clinic to prevent angina pectoris and esophageal varices, to treat hereditary or familial
essential tremor disease, and to reduce peripheral physiological symptoms
of anxiety and migraine prophylaxis. NDL is present in conventional tablet preparation
used orally in the market. Its bioavailability is around 30%. In oral drug design, exposure to different conditions
of the gastrointestinal tract such as pH change from acidic to basic,
various enzymes and surfactants (such as lipases, pepsinogens, pepsins,
bile, etc.), gastrointestinal microbiota, mucus barrier, and epithelial
layer results in low bioavailability. Nadolol (NDL)
is classified as a Biopharmaceutics Classification System (BCS) Class
III drug, characterized by high solubility but low intestinal permeability.
This limited permeability represents a major barrier to oral bioavailability.
The lipophilicity of NDL, expressed as its partition coefficient (log
P), has been reported to be relatively low, supporting its poor membrane
permeability behavior. Therefore, formulation strategies that can
enhance intestinal permeability are of particular interest. In order to overcome these challenging conditions, there is a need
for a new generation of oral drug delivery systems such as microcapsules,
microspheres, microsponges, nanoparticles, polymeric micelles, dendrimers,
carbon nanotubes, solid lipid nanoparticles, liposomes, and microemulsions with a lower side effect profile and more effectiveness. While studies specifically exploring microemulsion-based
formulations of nadolol are limited, evidence from other drugs suggests
that microemulsion systems can improve intestinal uptake and pharmacokinetic
profiles by enhancing membrane transport and lymphatic uptake.