ABSTRACT
PURPOSE: The aim of the study was to find an appropriate method for determination of the attachment degree of polyethylene glycol (PEG) to poly(anhydride) nanoparticles. METHODS: The nanoparticles were modified with hydroxy-functionalized or with amino-functionalized PEGs. Three methods for their determination were applied and examined: in particular colorimetry, nuclear magnetic resonance ( (1) H-NMR), and elemental analysis (EA). RESULTS: The attachment degrees determined by (1) H-NMR and colorimetry were similar. The associated amounts of PEGs estimated on the basis of EA differed significantly than those determined by colorimetry and (1) H-NMR. CONCLUSION: The colorimetric determination was considered fast and simple technique, but (1) H-NMR contributed to more precise results.
Subject(s)
Nanoparticles/chemistry , Polyanhydrides/chemistry , Polyanhydrides/metabolism , Polyethylene Glycols/chemistry , Polyethylene Glycols/metabolism , Binding Sites , Drug Delivery Systems/methodsABSTRACT
Nanoparticles based on the poly(methyl vinyl ether-co-maleic anhydride) were pegylated with different types of PEGs, namely, two hydroxyl-functionalized PEGs (PEG and mPEG) and two amino-PEGs (DAE-PEG and DAP-PEG). The resulted nanoparticles demonstrated reduction of the negative surface charge compared to the non-modified particles. Further, in vivo experiments showed that all types of pegylated particles possessed higher affinity to adhere to intestinal rather than to the stomach mucosa. Higher bioadhesive potential was observed in the case of PEG-NP and DAE-PEG-NP which was attributed to the flexibility and specific properties of the surface "brush" layer of these particles. The lower bioadhesive potential of mPEG-NP was due to the low presence of coating "brush" layer, whereas for DAP-PEG-NP to the fact that the double end coupled chains ("loop"-conformation) were not available for intensive interactions with the mucosa. The observations made by optic microscopy illustrated an intracellular transport of PEG-NP in vivo with preferable location in the apical area of enterocytes.
Subject(s)
Drug Carriers , Nanoparticles/chemistry , Polyanhydrides/pharmacokinetics , Polyethylene Glycols/pharmacokinetics , Polymers/chemistry , Adhesiveness , Administration, Oral , Animals , Biological Transport , Delayed-Action Preparations/chemical synthesis , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Drug Delivery Systems , Enterocytes/metabolism , Gastric Mucosa/cytology , Gastric Mucosa/metabolism , Intestinal Absorption , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Particle Size , Polyanhydrides/chemical synthesis , Polyanhydrides/chemistry , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/chemistry , Rats , Rats, Wistar , Surface PropertiesABSTRACT
Poly(lactide-co-glycolide) nanoparticles loaded with pilocarpine hydrochloride were prepared by the high-pressure emulsification-solvent evaporation method. The nanoparticles were produced using polyvinylalcohol (PVA), carbomer (Carbopol 980) or poloxamer (Lutrol F-68) as stabilizers during emulsification. The influence of pressure and number of cycles on the nanoparticle properties was investigated. For comparison, nanoparicles without high-pressure treatment of the emulsion were made. The nanoparticle size, drug loading and release properties depended strongly on the homogenization pressure and number of cycles applied. Nanoparticles obtained without high pressure homogenization showed larger size and high values of polydispersity index, especially when carbopol and poloxamer were used as emulsifiers. Drug loading and encapsulation efficiency of all samples also decreased with pressure. The low drug loading could be due to two reasons. First, the high pressure promoted drug diffusion out of protoparticles during emulsification either by size reduction or shear forces. Secondly, the characteristics of the outer water phase of the emulsion also influenced the nanoparticle drug loading. This was proven by the different drug loadings measured when nanoparticles were made with PVA, carbopol or poloxamer at equal pressures applied. The main factor influencing the release properties of nanoparticles was the pressure used during emulsification. Faster drug release was observed from nanoparticles obtained after high-pressure emulsification compared to those prepared without homogenization of the emulsion.
Subject(s)
Miotics/administration & dosage , Nanotechnology/methods , Pilocarpine/administration & dosage , Acrylic Resins/chemistry , Drug Carriers/chemistry , Drug Compounding/methods , Drug Delivery Systems/methods , Emulsions , Excipients , Humans , Microspheres , Ophthalmic Solutions , Particle Size , Poloxamer , Polyglactin 910 , Polyvinyl Alcohol , PressureABSTRACT
AIM: To assess the efficacy and patient compliance of topical mononitrate hydrogel for the treatment of anal fissure. MATERIALS AND METHODS: Nineteen patients with symptomatic chronic anal fissures were randomly allocated to receive either active (10 patients) or placebo (nine patients) gel treatment. Rectal administration of hydrogel containing 0.2% isosorbide-5-mononitrate was prescribed. Patients were instructed on its application to the anal canal twice daily for 3 weeks. A questionnaire was used to determine patient compliance with therapy. Anal manometry was performed before and after therapy. RESULTS: At the end of therapy, the fissures were healed in 80% of actively treated patients compared with 22% of the control group. There was a mean reduction of 28% in mean resting anal pressure. Two actively treated patients (20%) suffered from mild headache relieved with oral analgesics and menthol lozenges. Faecal incontinence was not observed. There were no recurrences during at least 3 months of follow-up. CONCLUSIONS: Topical mononitrate gel therapy of anal fissures is an effective and safe approach. In this study, the few cases of headache were rapidly relieved with oral analgesia and menthol lozenges.
Subject(s)
Fissure in Ano/drug therapy , Isosorbide Dinitrate/pharmacology , Vasodilator Agents/pharmacology , Administration, Topical , Adult , Aged , Female , Fissure in Ano/pathology , Humans , Hydrogels , Isosorbide Dinitrate/administration & dosage , Isosorbide Dinitrate/analogs & derivatives , Male , Manometry , Middle Aged , Patient Compliance , Placebos , Treatment Outcome , Vasodilator Agents/administration & dosageABSTRACT
Biodegradable cross-linked microspheres containing up to 63 wt.% of the active substance were obtained in a polycondensation process between D,L-malic acid and the tetrahydroxy compound dipyridamole. The in vitro release mechanism from biodegradable cross-linked microspheres has been studied. It was found that dipyridamole was released due to two-step hydrolysis of the ester bonds of the network. Initially, the only product of the hydrolytic degradation was found to be an oligomeric ester fraction with M(w)=1000 Da. The release of the free drug started after 8 days due to a further hydrolysis of the oligomers in solution. It was found that blood plasma enzymes in rats did not affect the hydrolytic processes. Biodegradable poly(malate) microspheres containing an anti-aggregating agent dipyridamole can be considered as a novel drug delivery system for a prolonged period of time implying a future parenteral application.
