Production of haloperidol loaded PLGA nanoparticles for extended controlled drug release of haloperidol

This study developed an emulsion-solvent evaporation method for producing haloperidol-loaded PLGA nanoparticles with up to 2% (wt/wt. of polymer) drug content, in vitro release duration of over 13 days and less than 20% burst release. The free haloperidol is removed from the nanoparticle suspension using a novel solid phase extraction technique. This leads to a more accurate determination of drug incorporation efficiency than the typical washing methods. It was discovered that PLGA end groups have a strong influence on haloperidol incorporation efficiency and its release from PLGA nanoparticles. The hydroxyl-terminated PLGA (uncapped) nanoparticles have a drug incorporation efficiency of more than 30% as compared to only 10% with methyl-terminated PLGA (capped) nanoparticles. The in vitro release profile of nanoparticles with uncapped PLGA has a longer release period and a lower initial burst as compared to capped PLGA. By varying other processing and materials parameters, the size, haloperidol incorporation and haloperidol release of the haloperidol-loaded PLGA nanoparticles were controlled

Controlling the \u3cem\u3eIn Vitro\u3c/em\u3e Release Profiles for a System of Haloperidol-Loaded PLGA

We have used a systematic methodology to tailor the in vitro drug release profiles for a system of PLGA/PLA nanoparticles encapsulating a hydrophobic drug, haloperidol. We applied our previously developed sonication and homogenization methods to produce haloperidol-loaded PLGA/PLA nanoparticles with 200–1000 nm diameters and 0.2–2.5% drug content. The three important properties affecting release behavior were identified as: polymer hydrophobicity, particle size and particle coating. Increasing the polymer hydrophobicity reduces the initial burst and extends the period of release. Increasing the particle size reduces the initial burst and increases the rate of release. It was also shown that coating the particles with chitosan significantly reduces the initial burst without affecting other parts of the release profile. Various combinations of the above three properties were used to achieve in vitro release of drug over a period of 8, 25 and \u3e40 days, with initial burst \u3c25% and a steady release rate over the entire period of release. Polymer molecular weight and particle drug content were inconsequential for drug release in this system. Experimental in vitro drug release data were fitted with available mathematical models in literature to establish that the mechanism of drug release is predominantly diffusion controlled. The average value of drug diffusivities for PLGA and PLA nanoparticles was calculated and its variation with particle size was established

Design of vitamin E d-α-Tocopheryl Polyethylene Glycol 1000 Succinate-Emulsified Poly (D,L–Lactide–co-Glycolide) Nanoparticles: Influence of Duration of Ultrasonication Energy

The aim of this research was to investigate the effect of the duration of ultrasonication energy on the physicochemical characteristics of the nano–sized particulate drug delivery systems. For this purpose, meloxicam-loaded vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-emulsified poly (D,L–lactide–co-glycolide) (PLGA) nanoparticles were designed by using ultrasonication-solvent evaporation technique and were characterized by photon correlation spectroscopy for size and size distribution, scanning electron microscopy for surface morphology and laser Doppler anemometry for surface charge. Ultraviolet -spectrophotometer was used to measure the drug encapsulation efficiency and to obtain in vitro drug release profile. The results showed that the physicochemical properties of the prepared nanoparticles are effectively controlled by the amount of shear stress transferred from the energy source to the emulsion, which is strongly correlated to the ultrasonication time

Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part I. Effect of process variables on the mean size

PLGA (poly d,l-lactic-co-glycolic acid) nanoparticles (NPs) encapsulating magnetite nanoparticles (MNPs) along with a model drug human serum albumin (HSA) were prepared by double emulsion solvent evaporation method. This Part I will focus on size and size distribution of prepared NPs, whereas encapsulation efficiency will be discussed in Part II. It was found that mean hydrodynamic particle size was influenced by five important process variables. To explore their effects, a five-factorial, three-level experimental design and statistical analysis were carried out using STATISTICA® software. Effect of process variables on the mean size of nanoparticles was investigated and finally conditions to minimize size of NPs were proposed. GAMS™/MINOS software was used for optimization. The mean hydrodynamic size of nanoparticles ranged from 115 to 329 nm depending on the process conditions. Smallest possible mean particle size can be achieved by using low polymer concentration and high dispersion energy (enough sonication time) along with small aqueous/organic volume ratio

Fabrication, Modeling and Characterization of Multi-Crosslinked Methacrylate Copolymeric Nanoparticles for Oral Drug Delivery

Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and characterized for particle size, zeta potential, morphology, structural modification, drug entrapment efficiency and in vitro drug release. Chemometric Computational (CC) modeling was conducted to deduce the mechanism of nanoparticle synthesis as well as to corroborate the experimental findings. The CC modeling deduced that the nanoparticles synthesis may have followed the mixed triangular formations or the mixed patterns. They were found to be hollow nanocapsules with a size ranging from 152 nm (methacrylate copolymer) to 321 nm (methacrylate copolymer blend) and a zeta potential range of 15.8–43.3 mV. The nanoparticles were directly compressible and it was found that the desired rate of drug release could be achieved by formulating the nanoparticles as a nanosuspension, and then directly compressing them into tablet matrices or incorporating the nanoparticles directly into polymer tablet matrices. However, sustained release of MCNs was achieved only when it was incorporated into a polymer matrix. The experimental results were well corroborated by the CC modeling. The developed technology may be potentially useful for the fabrication of multi-crosslinked polymer blend nanoparticles for oral drug delivery

Achieving long-term controlled drug delivery by using biodegradable polymeric nanoparticles

Long-term drug delivery has advantages over traditional drug delivery, including better patient compliance, increased effectiveness of drugs and reduction of side effects. A promising way to achieve long-term controlled drug delivery is to use drug-loaded biodegradable polymeric nanoparticles. A specific problem in using nanoparticles for controlled drug delivery is to control the duration of action and the rate and amount of drug released at any time. We have addressed this problem by using a system of a model hydrophobic drug, haloperidol encapsulated in a biodegradable polymer, poly(lactide-co-glycolide acid) (PLGA). We have developed emulsion-solvent evaporation methods for producing haloperidol-loaded PLGA nanoparticles with up to 2.5% (wt/wt. of polymer) drug content, in-vitro release duration of 13-40 days and less than 20% burst release. The free haloperidol is removed from the nanoparticle suspension using a novel solid phase extraction technique. The size of nanoparticles was effectively controlled in the range of 220-1000 nm by choosing appropriate preparation method and processing conditions, including polymer concentration in the organic phase and energy added. The drug content was controlled by increasing the drug-polymer interaction and decreasing drug diffusion into the aqueous phase. We have discovered that PLGA end groups have a strong influence on haloperidol incorporation efficiency and its release from PLGA nanoparticles. The drug incorporation efficiency with uncapped PLGA was three times that with capped PLGA. The in-vitro release profile of nanoparticles with uncapped PLGA had a longer release period and a lower initial burst as compared to capped PLGA. We established that the in-vitro release is predominantly diffusion controlled by comparing our experimental data with theoretical models. The release is strongly dependent on the size of particles and the polymer hydrophobicity. We have seen that coating the particles with chitosan prolongs the release and reduces the burst. The drug release profiles were tailored to achieve specific objectives in terms of release duration, rate of release, and release amount by simultaneously manipulating multiple parameters and properties

Achieving long-term controlled drug delivery by using biodegradable polymeric nanoparticles

Long-term drug delivery has advantages over traditional drug delivery, including better patient compliance, increased effectiveness of drugs and reduction of side effects. A promising way to achieve long-term controlled drug delivery is to use drug-loaded biodegradable polymeric nanoparticles. A specific problem in using nanoparticles for controlled drug delivery is to control the duration of action and the rate and amount of drug released at any time. We have addressed this problem by using a system of a model hydrophobic drug, haloperidol encapsulated in a biodegradable polymer, poly(lactide-co-glycolide acid) (PLGA). We have developed emulsion-solvent evaporation methods for producing haloperidol-loaded PLGA nanoparticles with up to 2.5% (wt/wt. of polymer) drug content, in-vitro release duration of 13-40 days and less than 20% burst release. The free haloperidol is removed from the nanoparticle suspension using a novel solid phase extraction technique. The size of nanoparticles was effectively controlled in the range of 220-1000 nm by choosing appropriate preparation method and processing conditions, including polymer concentration in the organic phase and energy added. The drug content was controlled by increasing the drug-polymer interaction and decreasing drug diffusion into the aqueous phase. We have discovered that PLGA end groups have a strong influence on haloperidol incorporation efficiency and its release from PLGA nanoparticles. The drug incorporation efficiency with uncapped PLGA was three times that with capped PLGA. The in-vitro release profile of nanoparticles with uncapped PLGA had a longer release period and a lower initial burst as compared to capped PLGA. We established that the in-vitro release is predominantly diffusion controlled by comparing our experimental data with theoretical models. The release is strongly dependent on the size of particles and the polymer hydrophobicity. We have seen that coating the particles with chitosan prolongs the release and reduces the burst. The drug release profiles were tailored to achieve specific objectives in terms of release duration, rate of release, and release amount by simultaneously manipulating multiple parameters and properties