Protein delivery using nanoparticles based on microemulsions with different structure-types (original) (raw)
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Microemulsion-based approach for oral delivery of insulin: formulation design and characterization
Heliyon, 2020
Oral delivery of insulin provides a good alternative because it is non-invasive and patient-friendly. However, multiple challenges affected this route. To overcome barriers for oral delivery of insulin, we aimed to develop a novel insulin-loaded microemulsion system based on snail mucin for oral administration. The strategy in the novel system of using mucin loading insulin into the inner core of prepared water in oil microemulsion to provide sustained released, increased in vivo stability and enhanced drug absorption in the gastrointestinal tract. We report how microemulsion composed of varying ratios of snail mucin and Tween® 80 (1:9–9:1) using oil/water emulsion preparation method influenced insulin performance after oral administration. The results obtained include an encapsulation efficiency of above 70 %; in vitro release was sustained over 10 h and in vivo evaluations in diabetic rat model shows that insulin-loaded microencapsulation effectively reduced blood glucose levels over a period >8 h after oral administration. Therefore, we suggest that the developed formulation for oral insulin can be a promising alternative dosage form for oral protein delivery.
Colloids and Surfaces B-biointerfaces, 2009
Biodegradable polymeric microspheres are ideal vehicles for controlled delivery applications of drugs, peptides and proteins. Amongst them, poly(lactic-co-glycolic acid) (PLGA) has generated enormous interest due to their favorable properties and also has been approved by FDA for drug delivery. Insulin-loaded PLGA microparticles were prepared by our developed single phase oil in oil (o/o) emulsion solvent evaporation technique. Insulin, a model protein, was successfully loaded into microparticles by changing experimental variables such as polymer molecular weight, polymer concentration, surfactant concentration and stirring speed in order to optimize process variables on drug encapsulation efficiency, release rates, size and size distribution. A 2 4 full factorial design was employed to evaluate systematically the combined effect of variables on responses. Scanning electron microscope (SEM) confirmed spherical shapes, smooth surface morphology and microsphere structure without aggregation. FTIR and DSC results showed drug-polymer interaction. The encapsulation efficiency of insulin was mainly influenced by surfactant concentration. Moreover, polymer concentration and polymer molecular weight affected burst release of drug and size characteristics of microspheres, respectively. It was concluded that using PLGA with higher molecular weight, high surfactant and polymer concentrations led to a more appropriate encapsulation efficiency of insulin with low burst effect and desirable release pattern.
Microemulsion as drug delivery system for Peptides and Proteins
2018
Microemulsions (MEs) are isotropic mixtures with or without a cosurfactant along with combination of oil, water and surfactant and most stable as per view of thermodynamics. These systems of drug delivery are currently of prior interest to the pharmacists because of their embryonic potential to act as therapeutic enzymes and peptide based drug delivery vehicles with incorporation of a wide range of active therapeutic protein and peptide molecules. These therapeutic macromolecules in microemulsion drug delivery form is not solely based on compositions of the vehicle but also on the internal structure or composition of the phases which may nurture protein drug distribution in the vehicles for enhanced drug solubilisation capacity, ease of preparation, enhancement of bioavailability and maximum shelf life. In order to appreciate the potential of protein based microemulsions as delivery vehicles for enhanced drug permeation via skin and tolerability of these systems, this review offers ...
European Journal of Pharmaceutics and Biopharmaceutics, 2010
Insulin loaded microemulsions were developed adopting a low shear reverse micellar approach using didoceyldimethylammonium bromide (DMAB) as the surfactant, propylene glycol (PG) as the co-surfactant, triacetin (TA) as the oil phase and insulin solution as the aqueous phase. A ternary phase diagram was constructed based on multiple cloud point titration to highlight the reverse micellar region. The droplet sizes of the microemulsions were 161.7 ± 24.7 nm with PDI of 0.447 ± 0.076 and insulin entrapment of $85%. Transmission electron microscopy (TEM) revealed the spherical nature and size homogeneity of the microemulsion droplets. The conformational stability of the entrapped insulin within microemulsions was confirmed by fluorescence spectroscopy and circular dichroism. The microemulsions displayed a 10-fold enhancement in bioavailability compared with plain insulin solution administered per oral in healthy rats. The short-term in vivo efficacy in STZ induced diabetic rats provided the proof of concept by a modest glucose reduction at a dose of 20 IU/kg. Together this preliminary data indicate the promise of microemulsions for oral delivery of insulin.
POLYMERIC MICROPARTICLES FORMULATION OF INSULIN FOR ORAL DRUG DELIVERY
Aim: To investigate the use of polymers with mucoadhesive properties. Method: Microparticles were formed using double emulsion technique (w/o/w) with the insulin loaded at the core of the particles. Gelatin, Polyethylene glycol 4000 (PEG-4000), Eudragit® S 100, snail mucin and sodium alginate polymers were combined at different ratios and investigated. The subsequent batches, W (Gelatin-PEG 4000), were characterized for particle size, morphology and polydispersity index (PDI). The stability of the formulations were evaluated using pH and Differential Scanning Calorimeter (DSC). In vitro drug release profile and in vivo study using diabetic rat model were carried out on the formulations. Results: The batches in W, had rough spherical shapes except for batch Z3 which was rod-like and smooth. Particle size ranged from 12.24 µm ± 0.1 to 23.57 µm ± 2.3 (batch W). PDI of the optimized batches were W2 (0.884 ± 0.11), W3 (0.431 ± 0.30), W5 (0.407 ± 0.64). The pH of the formulations showed an increase from 6.4 to 6.6 (at 24 h) to 7.4 – 7.8 (after one month) on storage for batches W, indicating a secondary microbial degradation. The encapsulation efficiency across all batches were greater than 76.4 %, and the loading capacities were between 2.48 to 5.24 %. The DSC thermogram showed that when compared with a commercial sample of insulin, that the sub-batches of batch W showed greater stability than the reference sample. Conclusion: Polymers of mucoadhesive properties can be used to formulate insulin for oral drug delivery, and they also have potential control release ability. Keywords: Diabetes mellitus, Insulin, Microparticles, Polymers.
Journal of Pharmaceutical Sciences, 1996
0 Phase diagrams containing the microemulsion region were constructed for pseudo-ternary systems composed of polyglycerol fatty acid ester/cosurfactant/Captex 300/water. It was found necessary to add ethanol, 1-propanol, or 1-butanol as cosurfactant to produce microemulsions. The results also demonstrated microemulsions were only able to form when employing polyglycerol fatty acid esters with hydrophile− lipophile balances (HLBs) between 8 and 13, such as MO500, MO750, SO750, and ML310. Most microemulsions were determined to be Winsor type IV by dilution and dye solubility tests. Microemulsions stored at ambient temperature maintained constant viscosity, indicating that the system was thermodynamically stable for long periods. Further, several microemulsion formulations were demonstrated to be promising for oral delivery of insulin based on the results of stability tests and acid-protection efficiency.
Development and evaluation of microemulsions for transdermal delivery of insulin
ISRN pharmaceutics, 2011
Insulin-loaded microemulsions for transdermal delivery were developed using isopropyl myristate or oleic acid as the oil phase, Tween 80 as the surfactant, and isopropyl alcohol as the cosurfactant. The pseudoternary phase diagrams were constructed to determine the composition of microemulsions. The insulin permeation flux of microemulsions containing oleic acid as oil phase through excised mouse skin and goat skin was comparatively greater than that of microemulsions containing isopropyl myristate as oil phase. The insulin-loaded microemulsion containing 10% oleic acid, 38% aqueous phase, and 50% surfactant phase with 2% dimethyl sulfoxide (DMSO) as permeation enhancer showed maximum permeation flux (4.93 ± 0.12μg/cm2/hour) through goat skin. The in vitro insulin permeation from these microemulsions was found to follow the Korsmeyer-Peppas model (R2 = 0.923 to 0.973) over a period of 24 hours with non-Fickian, “anomalous” mechanism. Together these preliminary data indicate the promise of microemulsions for transdermal delivery of insulin.
Design and Development of Oral Nanoparticulated Insulin in Multiple Emulsion
The present research aimed at developing an injection-free nanoparticulated formulation in multiple emulsion form, for oral delivery of insulin, which otherwise undergoes degradation in the gastric environment if administered orally. Insulin-polymeric nanoparticles were prepared using layer by layer (LbL) adsorption method and incorporated into an emulsion to form a nanoparticulated multiple emulsion. Using 0.6 M sodium chloride, the insulin nanoaggregates of 300-400 nm size were obtained about a yield of 94%. The characteristics of a representative nanoparticle were as follows: particle size - 391.9±0.41 nm, polydispersity index -0.425, zeta potential- +20.6 mv, encapsulation efficiency- 86.7±1.42% and percentage entrapment efficiency of the insulin-polymeric nanoparticles in the inner aqueous phase of emulsion was 84.6 %. The FT-IR analysis confirms that there were no drug interactions with the polymers. Stability analysis carried out for 3 months at 8-40 °C, showed only minor changes at the end period. The release kinetics of the nanoparticulated multiple emulsion at pH 7.4 followed first order kinetics and obeyed the Fickian law. However, at pH 2.0 the release kinetics from nanoparticulated multiple emulsion followed zero order kinetics without obeying to the Fickian law. In conclusion, our data demonstrate that the nanoparticulated multiple emulsion formulation has good release characteristics and imparted a tolerable protection for insulin at different pH conditions, which may be exploited for oral administration.
Microemulsions for protein delivery: loading optimization and stability
Current pharmaceutical biotechnology, 2017
Microemulsions are attractive delivery systems for therapeutic proteins and peptides due to their ability to enhance bioavailability. Although different proteins and peptides have been successfully delivered through such ternary systems, no information can be found about protein loading and the formulation stability when such microemulsions are prepared with pharmaceutically-approved oils and surfactants. The aim of this work was to optimise a ternary system consisting of water/ethyl oleate/Span 80-Tween 80 and to determine its protein loading capacity and stability, using bovine serum albumin (BSA) as a model of biomolecule. The optimization was carried out using a Central Composite Design and all the prepared formulations were characterised through dynamic light scattering, rheology, optical and polarized microscopy. Subsequently, the maximum loading capacity was determined and the stability of the final microemulsion with the highest content of protein was followed over six mon...
Progress in Biomaterials
The objective of the present investigation was to formulate and characterize the human insulin entrapped Eudragit S100 microspheres containing protease inhibitors and to develop an optimized formulation with desirable features. A w/o/w multiple emulsion solvent evaporation technique was employed to produce microspheres of human insulin using Eudragit S-100 as coating material and polyvinyl alcohol as a stabilizer. The resultant microspheres were evaluated for drug-excipient compatibility, encapsulation efficiency, particle size, surface morphology, micromeritic properties, enteric nature, and in vitro drug release studies. Micromeritic properties indicated good flow properties and compressibility. In present investigation formulation F6 with drug/polymer ratio (1:100) was