Release of dexamethasone from PLGA nanoparticles entrapped into dextran/poly(vinyl alcohol) hydrogels

Hydrogels based on blends of poly(vinyl alcohol) (PVA) with dextran were prepared by a physical cross-linking procedure and used as matrices for the entrapment of biodegradable nanoparticles loaded with dexamethasone. The nanoparticles were prepared, by a solvent evaporation technique, using biodegradable copolymers of poly(lactic acid)–poly(glycolic acid) (PLGA). Size, morphology and surface characteristics of the nanoparticles were evaluated by scanning electron microscopy. The mechanism of drug release from the nanoparticles entrapped into the PVA-based matrices was studied and compared to that from free nanoparticles. The effect of dextran on the in vitro release profile of dexamethasone from the hydrogels was investigated. The obtained results indicate that PLGA nanoparticles are able to release dexamethasone following a diffusion-controlled mechanism. The entrapment of the nanoparticles into the hydrogels affects only slightly this mechanism of drug release. In addition, dextran/PVA hydrogels release a higher amount of drug with respect to pure PVA hydrogels and by increasing dextran content in the hydrogels, the amount of drug released increases.     

Controlled release of insulin from PLGA nanoparticles embedded within PVA hydrogels

A simple and versatile delivery platform for peptide and protein based on physically cross-linked poly (vinyl alcohol) (PVA) hydrogels containing insulin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles was successfully fabricated. The particle morphology and size were characterized by SEM and laser light scattering method, respectively. Results showed that these particles had a mean diameter of 615 nm with a narrow size distribution and homogeneous particle production. The protein encapsulation efficiency was 72.6%. When insulin-loaded PLGA nanoparticles were administered intraperitoneally as a single dose (20 U/kg) to streptozotocin-induced diabetic mouse, blood glucose levels of these mice decreased and it could be sustained at such levels over 24 h. In vitro release further indicated that entrapment of the nanoparticles into the PVA hydrogels causes a reduction in both the release rate and the total amount of insulin released, which suggesting that PLGA nanoparticles entrapped into the PVA hydrogels showed more suitable controlled release kinetics for protein delivery.     

Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour).     

Paclitaxel-loaded lipid nanoparticles prepared by solvent injection or ultrasound emulsification

Lipid nanoparticles were fabricated as an injectable carrier system for paclitaxel. The components for the lipid matrix were based on phospholipids, and sucrose fatty acid ester was used as an emulsifier. Formulation prepared with solvent injection has a slightly larger particle size (187.6 nm) than the formulation (147.7 nm) prepared with ultrasound emulsification. Differential scanning calorimetry results indicated that paclitaxel entrapped in the lipid nanoparticles existed in an amorphous state in the lipid matrix. In vitro drug release was rather slow; only 12.5-16.5% of the drug released from the formulations within 14 days. Lipid nanoparticles demonstrated their potential as a promising pharmaceutical formulation of paclitaxel.     

Paclitaxel-Loaded Lipid Nanoparticles Prepared by Solvent Injection or Ultrasound Emulsification

ABSTRACT

Lipid nanoparticles were fabricated as an injectable carrier system for paclitaxel. The components for the lipid matrix were based on phospholipids, and sucrose fatty acid ester was used as an emulsifier. Formulation prepared with solvent injection has a slightly larger particle size (187.6 nm) than the formulation (147.7 nm) prepared with ultrasound emulsification. Differential scanning calorimetry results indicated that paclitaxel entrapped in the lipid nanoparticles existed in an amorphous state in the lipid matrix. In vitro drug release was rather slow; only 12.5–16.5% of the drug released from the formulations within 14 days. Lipid nanoparticles demonstrated their potential as a promising pharmaceutical formulation of paclitaxel.     

Design of gelatin nanoparticles as swelling controlled delivery system for chloroquine phosphate

Gelatin nanoparticles were prepared by a single W/O emulsion technique and characterized by infrared (IR) spectra, scanning electron microscopy (SEM) and particle size analysis. The prepared nanoparticles were loaded with chloroquine phosphate (CP), a well known antimalarial drug, and the release dynamics of entrapped drug was investigated as a function of various experimental factors such as percent loading of the drug, chemical architecture of the nanocarriers, and pH, temperature, ionic strength and nature of the release medium. The nanoparticles were also studied for their water sorption capacity by optical microscopic method taking advantage of the aggregation of nanoparticles. The drug release processes was analyzed kinetically using Ficks power law and a correlation was established between the quantity of released drug and swelling of the nanoparticles.     

In vitro evaluation of betamethasone-loaded nanoparticles

The aim of the present work was to investigate the preparation of nanoparticles as a potential drug carrier in the treatment of various inflammatory diseases. A nanoprecipitation method was used to entrap betamethasone in a poly[ε-caprolactone] matrix. Process parameters such as the initial drug load, the surfactants (polyvinyl alcohol, PVA; sodium cholate, SC), and their concentration in the aqueous phase were analyzed for their influences on particle properties. Particle size changed with increasing surfactant concentrations (PVA: 250 to 400 nm; sodium cholate: 330 to 150 nm) due to changes in interface stability and viscosity of the aqueous phase. The zeta potential was around neutrality with PVA and between - 28 and - 42 mV with SC. Betamethasone encapsulation rates of about 75% and 90% slightly increased with higher surfactant concentration. Drug release profiles exhibited an initial burst release with both surfactants, PVA (8-18%) or SC (25-35%) followed by a sustained release delivering 15% to 40% of the entrapped drug within 48 hours. The present nanoparticulate formulations exhibit promising properties of a colloidal drug carrier for betamethasone. Although SC seems to be advantageous due to its biocompatibility, in terms of sustained drug release pattern, the use of PVA is favorable.     

Hydrogels based on chitosan and dextran as potential drug delivery systems

The release of human growth hormone (GH) from bioartificial polymeric materials in the form of hydrogels, was measured in vitro for up to 3 weeks. Poly(vinyl-alcohol) (PVA) was blended, in different ratios, with two biological polymers, dextran and chitosan respectively. These blends were used to prepare hydrogels, using a freeze–thawing method. The hydrogels were loaded with GH, and their potential use as delivery systems was investigated. The release with time of PVA, in aqueous medium, was also monitored and evaluated. Scanning electron microscopy was used to investigate the structure of the hydrogels. The results obtained indicated that GH can be released from both dextran/PVA and chitosan/PVA hydrogels. The initial GH concentration used for sample loading affected the total quantity of GH released but not the pattern of release. The amount of GH released was affected by the content of the biological component. The percentage of PVA released was low but it was, however, related to the content of chitosan and dextran in the blends. ©1999 Kluwer Academic Publishers     

Porous hollow silica nanoparticles as carriers for controlled delivery of ibuprofen to small intestine

With two different methods, ibuprofen was entrapped into porous hollow silica nanoparticles (PHSNs) carriers, which were synthesized through a sol-gel route by using CaCO3 nanoparticles as the inorganic templates. By employing pressured CO2 as the loading medium, the amount of ibuprofen that was pressed into the carriers was approximately 52% higher than that by simply soaking. The drug release behaviors of the ibuprofen-loaded PHSNs were investigated in a simulated intestine juice and an artificial gastric fluid, respectively, and it demonstrated a sustained release pattern in all cases and the sample prepared under high pressure had a lower release rate in both fluids and thus owned a greater sustained drug release capacity. In the acidic artificial gastric fluid, no silica was degraded and only 16% of the loaded ibuprofen was released from the matrix in 300 min. However, much more silica was degraded in the simulated intestine juice in a shorter time and almost all the loaded ibuprofen was dissolved into the solution eventually, resulting in a quicker and complete ibuprofen release. Therefore, the PHSNs can be utilized for applications of controlled drug delivery to small intestine.     

Gelatin nanoparticles produced by a simple W/O emulsion as delivery system for methotrexate

Biodegradable hydrophilic gelatin nanoparticles, containing different initial amounts of methotrexate (MTX), were prepared using a simple solvent evaporation technique based on a single water-in-oil emulsion and stabilized by the use of glutaraldehyde as cross-linking agent. The effects of several parameters on particle size, drug encapsulation efficiency and drug release were investigated. Size and shape of the nanoparticles were examined by scanning electron microscopy. The release of MTX was monitored in vitro and the mechanism of release was studied. Particles with a mean diameter of 100–200 nm were produced, which were able to release MTX following a diffusion-controlled mechanism of release. It was observed that the initial amount of MTX used for sample loading did not have any effect on the pattern of release, while it affected the amount of drug entrapped into the nanoparticles and also both the release rate and the total amount of drug released.     

Physically cross-linked polyvinyl alcohol for the topical delivery of fluconazole

The aim of this study was to develop fluconazole in an ultrapure polyvinyl alcohol (PVA) hydrogel able to deliver the drug in a sustained release pattern for local treatment of skin fungal infections. The topical fluconazole hydrogels were prepared using PVA hydrogels physically cross-linked by freeze-thaw technique. Polyethylene glycol (PEG) was added as a hydrophilic excipient as a release enhancer of fluconazole. The effects of PVA molecular weight, PEG molecular weight, and PEG concentration were studied using a 2 x 4 x 2 factorially designed experiment. The selected fluconazole hydrogel proved to be physically stable over a period of 6 months and to be effective in the topical treatment of cutaneous candidiasis. Therefore, it could be concluded that the formula composed of 10% PVA 205000 and 1.5% PEG 4000 and 2% fluconazole and prepared by three cycles of freezing, and thawing is very promising in the local treatment of skin fungal infection as an alternative to the systemic use of fluconazole.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Investigation of a novel freeze-thaw process for the production of drug delivery hydrogels

Poly(vinyl alcohol) (PVA) is a water-soluble, biocompatible and biodegradable polymer, which has been widely applied in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of PVA and comprising a blend of poly(vinyl alcohol) (PVA) with different concentrations of HCl, NaOH and NaCl are prepared by a freezing/thawing treatment of aqueous solutions. The structure and complexation of the electrolytes were studied by Fourier transform infrared (FTIR) spectroscopy. The mechanical properties were investigated using rheometery and the thermal transitions of the hydrogels were examined by modulated differential scanning calorimetry (MDSC). Freeze/thawed PVA gels containing NaOH showed overall enhanced swelling with increased mechanical strength over traditional gels prepared by chemical or irradiative crosslinking techniques. These novel physically cross-linked hydrogels show promise for a variety of biomedical and drug delivery applications.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

短纤维复合聚乙烯醇水凝胶的力学性能

研究了PVA短纤维复合PVA水凝胶的制备以及影响其力学性能的因素,包括二甲基亚砜(DM-SO)/水混合溶剂和纯水溶剂两种体系。凝胶采用低温冷冻-高温解冻循环方法制备。在加入少量PVA短纤维后,材料强度降低,随着纤维添加量的增加,凝胶的强度提高。当PVA短纤维添加量超过临界含量时,复合凝胶强度高于凝胶基体强度。     

Investigation on magnetically controlled delivery of doxorubicin from superparamagnetic nanocarriers of gelatin crosslinked with genipin

Gelatin (Type B) nanoparticles were prepared by a single W/O emulsion technique and characterized by infrared (IR) spectra, transmission electron micrographs (TEM), surface potential measurements and magnetization studies. Whereas the IR spectra clearly confirmed the presence of gelatin, genipin and doxorubicin in the loaded nanoparticles, the transmission electron micrographs (TEM) image depicts smooth surface, spherical shape and non-uniform size of nanoparticles (up to 100 nm). The prepared nanoparticles were loaded with doxorubicin, a well known anticancer drug, and in vitro release dynamics of entrapped drug was investigated as a function of various experimental factors such as percent loading of the drug, chemical architecture of the nanocarriers, and pH, temperature, ionic strength and nature of the release medium in presence and absence of magnetic field. The nanoparticles were also studied for their water sorption capacity. The drug release process was analyzed kinetically using Ficks power law and a correlation was established between the quantity of released drug and swelling of the nanoparticles.     

Synthesis and characterization of polycaprolactone/acrylic acid (PCL/AA) hydrogel for controlled drug delivery

In the present work biodegradable pH-sensitive polycaprolactone/acrylic acid (PCL/AA) hydrogels have been developed using ethylene glycol dimethacrylate (EGDMA) as a cross-linker and benzoyl peroxide as initiator. For these prepared hydrogels swelling studies, sol-gel fraction analysis and porosity measurements were performed. Results show that swelling of the hydrogels decreases on increasing the concentration of PCL and EGDMA, however swelling of hydrogels increases on increasing the concentration of AA. Results of sol-gel fraction analysis show that gel fraction increases on increasing concentration of monomer AA, polymer PCL as well as cross-linker EGDMA. As far as porosity is concerned, it increases on increasing the concentration of AA and PCL while porosity decreases on increasing the concentration of EGDMA. Hydrogels were characterized by measuring diffusion coefficient (D) and equilibrium water content (EWC). Network formation, morphology and crystallinity of PCL/AA hydrogels were investigated using FTIR, SEM and XRD, respectively. Tramadol hydrochloride was loaded as model drug and its release pattern was analysed using various kinetic models like zero order, first order, Higuchi and Peppas. Results indicated that most of the samples followed non-Fickian release mechanism.     

Studies on Pectins as Potential Hydrogel Matrices for Controlled-Release Drug Delivery

Polymeric hydrogels are widely used as controlled-release matrix tablets. In the present study, we investigated high-methoxy pectins for their potential value in controlled-release matrix formulations. The effects of compression force, ratio of drug to pectin, and type of pectin on drug release from matrix tablets were also investigated. The results of the in vitro release studies show that the drug release from compressed matrix tablets prepared from pectin can be modified by changing the amount and the type of pectin in the matrix tablets. However, compression force did not significantly affect the drug release. The mechanisms controlling release rate were discussed with respect to drug diffusion through the polymer matrices, but may be more complex.     

Studies on pectins as potential hydrogel matrices for controlled-release drug delivery

Polymeric hydrogels are widely used as controlled-release matrix tablets. In the present study, we investigated high-methoxy pectins for their potential value in controlled-release matrix formulations. The effects of compression force, ratio of drug to pectin, and type of pectin on drug release from matrix tablets were also investigated. The results of the in vitro release studies show that the drug release from compressed matrix tablets prepared from pectin can be modified by changing the amount and the type of pectin in the matrix tablets. However, compression force did not significantly affect the drug release. The mechanisms controlling release rate were discussed with respect to drug diffusion through the polymer matrices, but may be more complex.     

Aragonite Nanorods in Calcium Carbonate/Polymer Hybrids Formed through Self‐Organization Processes from Amorphous Calcium Carbonate Solution

Nanostructured inorganic/polymer hybrid thin films comprising aragonite nanorods derived from aqueous suspensions of amorphous calcium carbonate (ACC) are prepared. For the formation of calcium carbonate (CaCO₃)/polymer hybrids, spincoated and annealed films of poly(vinyl alcohol) (PVA) that function as polymer matrices are soaked in aqueous colloidal solutions dispersing ACC stabilized by poly(acrylic acid) (PAA). In the initial stage, calcite thin films form on the surface. Subsequently, aragonite crystals start to form inside the PVA matrix that contains PVA crystallites which induce aragonite nucleation. Nanostructured hybrids composed of calcite thin films consisting of nanoparticles and assembled aragonite nanorods are formed in the matrices of PVA.