Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

Metabolic abnormalities and catheter-related infections are common complications of parenteral nutrition (PN). Particulate contamination is a catheter-related complication can occur when administering PN: mixing the electrolytes, trace elements, vitamins into the PN, or puncturing a rubber stopper at the PN formulation. In addition, the aggregation of the components of the PN solution by a drug incompatibility reaction could be related to particulate contamination. PN contaminated with precipitates, insoluble particles, and bacteria was reported as the cause of the death of a patient. The Food and Drug Administration recommended that the filters be used during PN administration. In-line filters can retain the bacteria and insoluble particles in PN solutions, and prevent their infusion into the patient. Therefore, in-line filters are recommended to prevent catheter-related complications that can occur during PN infusion. A 0.2µ filter for lipid-free PN and a 1.2µ filter for lipid-containing PN solutions can be used. On the other hand, when a filter is applied, the infusion rate can decrease and the economic burden will increase for patients requiring long-term PN. In addition, small particles, such as viruses, polymers, and proteins cannot be filtered out completely. In conclusion, in-line filers are recommended to prevent catheter-related complications that can occur during PN administration, but there are no international standardized guidelines. Therefore, standardized guidelines will be needed based on evidence accompanied by clinical trials. In addition, in-line filter applications should be considered in the clinical field depending on the patient's condition.
Bacteria ; Catheter-Related Infections ; Drug Incompatibility ; Electrolytes ; Filtration ; Hand ; Humans ; Parenteral Nutrition ; Polymers ; Rubber ; Trace Elements ; United States Food and Drug Administration ; Vitamins

PURPOSE: Poloxamer 407 (P407) thermo-sensitive hydrogel formulations were developed to enhance the retention time in the urinary bladder after intravesical instillation. MATERIALS AND METHODS: P407 hydrogels (P407Gels) containing 0.2 w/w% fluorescein isothiocyanate dextran (FD, MW 4 kDa) as a fluorescent probe were prepared by the cold method with different concentrations of the polymer (20, 25, and 30 w/w%). The gel-forming capacities were characterized in terms of gelation temperature (G-Temp), gelation time (G-Time), and gel duration (G-Dur). Homogenous dispersion of the probe throughout the hydrogel was observed by using fluorescence microscopy. The in vitro bladder simulation model was established to evaluate the retention and drug release properties. P407Gels in the solution state were administered to nude mice via urinary instillation, and the in vivo retention behavior of P407Gels was visualized by using an in vivo imaging system (IVIS). RESULTS: P407Gels showed a thermo-reversible phase transition at 4℃ (refrigerated; sol) and 37℃ (body temperature; gel). The G-Temp, G-Time, and G-Dur of FD-free P407Gels were approximately 10℃–20℃, 12–30 seconds, and 12–35 hours, respectively, and were not altered by the addition of FD. Fluorescence imaging showed that FD was spread homogenously in the gelled P407 solution. In a bladder simulation model, even after repeated periodic filling-emptying cycles, the hydrogel formulation displayed excellent retention with continuous release of the probe over 8 hours. The FD release from P407Gels and the erosion of the gel, both of which followed zero-order kinetics, had a linear relationship (r²=0.988). IVIS demonstrated that the intravesical retention time of P407Gels was over 4 hours, which was longer than that of the FD solution ( < 1 hour), even though periodic urination occurred in the mice. CONCLUSIONS: FD release from P407Gels was erosion-controlled. P407Gels represent a promising system to enhance intravesical retention with extended drug delivery.
Administration, Intravesical* ; Animals ; Dextrans ; Drug Liberation ; Fluorescein ; Hydrogel* ; Hydrogels* ; In Vitro Techniques ; Kinetics ; Methods ; Mice* ; Mice, Nude ; Microscopy, Fluorescence ; Optical Imaging ; Phase Transition ; Poloxamer* ; Polymers ; Urinary Bladder* ; Urination

PURPOSE: Annually 27,855 patients in Korea develop treatment-induced mucositis nearly doubling the cost of cancer care. It is an emergency medical condition causing unplanned treatment breaks in 4,998 patients. The subsequent reduction in optimal dose-intensity causes premature deaths due to lower 5-year survival. An additional 216 patients die from mucositis-mediated sepsis and infection. Thus complete elimination of mucositis will immediately reduce the cost of care while simultaneously eliminating 5,214 mucositis-associated deaths. High potency polymerized cross-linked sucralfate (HPPCLS) cleared by the US Food and Drug Administration has been associated with the elimination of mucositis.METHODS: Observational, self-reporting, practice-based mucositis registry. Inclusion criteria: any patient with chemoradiation-induced mucositis. Exclusion criteria: previous adverse reaction to sucralfate products. Primary outcome: rapid reversal or complete prevention. Conduct of study: 28 radiation oncologists from 21 different institutions prescribed HPPCLS to 55 patients undergoing chemoradiation for squamous cell carcinoma of head and neck and esophagus to eliminate mucositis-associated treatment breaks.RESULTS: All patients with World Health Organization grade 1 (n=6), grade 2 (n=23), grade 3 (n=16) oral mucositis, and grade 2 esophageal mucositis (n=2) experienced complete reversal of mucositis. Within 2–3 days both mucosa and swallowing normalized. Anticipated grade 3/4 mucositis was prevented in 8 out of 8 elderly patients aged 78–93 avoiding gastrostomy tube placement. Statistical analysis of outcomes: Outcomes qualified as a positive Glasziou treatment effect that was statistically significant (P<0.05).CONCLUSION: HPPCLS eliminated mucositis by rapid reversal or complete prevention, thereby eliminating unplanned treatment breaks. It may likely reduce mucositis-associated increased cost of care and premature deaths.
Aged ; Carcinoma, Squamous Cell ; Deglutition ; Drug Therapy ; Emergencies ; Esophagus ; Gastrostomy ; Head and Neck Neoplasms ; Head ; Humans ; Korea ; Mortality, Premature ; Mucositis ; Mucous Membrane ; Neck ; Polymers ; Sepsis ; Stomatitis ; Sucralfate ; United States Food and Drug Administration ; World Health Organization

BACKGROUNDDespite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs) have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES), compared with traditional sirolimus-eluting stent (SES).

METHODSPatients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF), and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR) by telephone visit and late luminal loss (LLL) at 9-month by angiographic follow-up.

RESULTSFrom July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980). Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028). There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008).

CONCLUSIONSAfter 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

Aged ; Arsenicals ; administration & dosage ; therapeutic use ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; surgery ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Oxides ; administration & dosage ; therapeutic use ; Percutaneous Coronary Intervention ; methods ; Polymers ; chemistry ; Sirolimus ; administration & dosage ; therapeutic use

Some polymers and bioactive compounds derived from Styela clava tunic (SCT) have been reported as traditional medicine for the treatment of inflammation, oxidative stress and surgical wounds although there is little scientific evidence of their liver and kidney toxicity. To investigate the toxicity of ethanol extracts of SCT (EtSCT) in the liver and kidney of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed following oral administration of 50 and 100 mg/kg body weight/day of EtSCT for 14 days. EtSCT showed a high level of free radical scavenging activity for DPPH (93.1%) and NO (16.2%) as well as the presence of 14.8 mg/mL of flavonoids and 36.2 mg/mL of phenolics, while EtSCT treated groups did not show any significant alterations in the body and organ weight, clinical phenotypes, urine parameters or mice mortality when compared with the vehicle treated group. In addition, constant levels of serum biochemical markers including alanine phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (CRE) were maintained. Moreover, no specific histopathological features induced by most toxic compounds were observed in liver and kidney sections stained with hematoxilin and eosin. Therefore, the present results indicate that EtSCT with strong antioxidant activity cannot induce any specific toxicity in liver and kidney organs of ICR at doses of 100 mg/kg body weight/day.
Administration, Oral ; Alanine ; Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Biomarkers ; Blood Urea Nitrogen ; Body Weight ; Creatinine ; Eosine Yellowish-(YS) ; Ethanol ; Flavonoids ; Inflammation ; Kidney ; Liver ; Medicine, Traditional ; Mice ; Mice, Inbred ICR* ; Mortality ; Organ Size ; Oxidative Stress ; Pathology ; Phenol ; Phenotype ; Polymers ; Wounds and Injuries

BACKGROUNDDrug eluting stents (DESs) made with biodegradable polymer have been developed in an attempt to improve clinical outcomes. However, the impact of biodegradable polymers on clinical events and stent thrombosis (ST) remains controversial.

METHODSWe searched Medline, the Cochrane Library and other internet sources, without language or date restrictions for articles comparing clinical outcomes between biodegradable polymer DES and durable polymer DES. Safety endpoints were ST (definite, definite/probable), mortality, and myocardial infarction (MI). Efficacy endpoints were major adverse cardiac event (MACE) and target lesion revascularization (TLR).

RESULTSWe identified 15 randomized controlled trials (n = 17 068) with a weighted mean follow-up of 20.6 months. There was no statistical difference in the incidence of definite/probable ST between durable polymer- and biodegradable polymer- DES; relative risk (RR) 0.83; 95% confidence interval (CI) 0.62-1.11; P = 0.22. Biodegradable polymer DES had similar rates of definite ST (RR 0.94, 95% CI 0.66-1.33, P = 0.72), mortality (RR 0.94, 95% CI 0.82-1.09, P = 0.43), MI (RR 1.08, 95% CI 0.92-1.26. P = 0.35), MACE (RR 0.99, 95% CI 0.91-1.09, P = 0.85), and TLR (RR, 0.94, 95% CI 0.83-1.06, P = 0.30) compared with durable polymer DES. Based on the stratified analysis of the included trials, the treatment effect on definite ST was different at different follow-up times: ≤ 1 year favoring durable polymer DES and >1 year favoring biodegradable polymer DES.

CONCLUSIONSBiodegradable polymer DES has similar safety and efficacy for treating patients with coronary artery disease compared with durable polymer DES. Further data with longer term follow-up are warranted to confirm the potential benefits of biodegradable polymer DES.

Coronary Artery Disease ; drug therapy ; surgery ; Drug-Eluting Stents ; Humans ; Polymers ; administration & dosage ; Thrombosis

An HPLC method for the determination of geniposide concentration in mouse plasma was developed and the pharmacokinetics after intranasal administration of Xingnaojing microemulsion (XNJ-M) and mPEG2000-PLA modified Xingnaojing microemulsion (XNJ-MM) were investigated. Eighty mice were treated by XNJ-M and XNJ-MM nasally. The plasma samples were collected at different times and the drug in samples was detected by HPLC. The pharmacokinetic parameters were calculated by the software of Kinetica. The pharmacokinetic parameters of geniposide of XNJ-M were C(max) (4.36 +/- 2.69) mg x L(-1), t(max) 1 min, MRT (29.73 +/- 4.54) min, AUC (53.63 +/- 14.03) mg x L(-1) x min. The pharmacokinetic parameters of geniposide of XNJ-MM were C(max) (9.75 +/- 4.14) mg x L(-1), t(max) 1 min, MRT(22.34 +/- 2.90) min, AUC (131.87 +/- 40.13) mg x L(-1) x min. Geniposide can be absorbed into blood in a higher degree after intranasal administration with XNJ-MM compared to XNJ-M, which maybe caused by its less irritating and more absorption.
Animals ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Emulsions ; Iridoids ; blood ; pharmacokinetics ; Lactic Acid ; chemistry ; Male ; Mice ; Polyesters ; Polyethylene Glycols ; chemistry ; Polymers ; chemistry

The core-crosslinked polymeric micelles were used as a new drug delivery system, which can decrease the premature drug release in blood circulation, improve the stability of the micelles, and effectively transport the drug into the therapy sites. Then the drug bioavailability increased further, while the side effect reduced. Most drugs were physically entrapped or chemically covalent with the polymer in the internals of micelles. Based on the various constitutions and properties of polymeric micelles as well as the special characteristics of body microenvironment, the environment-responsive or active targeting core-crosslinked micelles were designed and prepared. As a result, the drug controlled release behavior was obtained. In the present paper, the research progress of all kinds of core-crosslinked micelles which were published in recent years is introduced. Moreover, the characteristic and application prospect of these micelles in drug delivery system are analyzed and summarized.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; therapeutic use ; Cross-Linking Reagents ; chemistry ; metabolism ; Drug Carriers ; chemistry ; metabolism ; Humans ; Micelles ; Molecular Structure ; Neoplasms ; drug therapy ; Particle Size ; Pharmaceutical Preparations ; administration & dosage ; Polyethylene Glycols ; chemistry ; metabolism ; Polymers ; chemistry ; metabolism

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.
Administration, Cutaneous ; Aerosols ; Animals ; Azepines ; chemistry ; Calorimetry, Differential Scanning ; Cellulose ; analogs & derivatives ; chemistry ; Citrates ; chemistry ; Drug Delivery Systems ; Estradiol ; administration & dosage ; pharmacokinetics ; Plasticizers ; chemistry ; Polymers ; chemistry ; Skin Absorption ; Swine