Preparation And Characterization Of Acyclovir Nanoparticles By Double Emulsion Technique

Acyclovir (ACV) is one of the most effective and selective agents against viruses of the Herpes group. Its t1/2 is about 2.5 hrs., hence repeated administration of high doses is required (200 mg 5 times daily). Parenteral ACV nanoparticles (NPs) for prolonged systemic delivery were prepared by w/o/w double emulsion (DE) technique using biodegradable polymers. The effect of formulation variables such as ratio of drug to polymer as well as the effect of polymer type [Polylactic acid (PLA), polylactic-co-glycolic (PLGA) 85/15, PLGA 75/25, PLGA 50/50] was studied. Dynamic light scattering system, transmission electron microscopy (TEM), zeta potential, differential scanning calorimetry (DSC) and X-ray powder diffractometry were employed to characterize the fabricated NPs for size and size distribution, surface morphology, surface charge and the physical state of drug in NPs respectively. Encapsulation efficiency (EE) and the in vitro release of ACV in NPs were investigated. Spherical NPs ranging between 590-770 nm in diameter with narrow size distribution were obtained. All particles exhibited a negative surface charge. ACV entrapped in NPs was found in the form of amorphous state. EE was in the range of 30.08% - 51.13%. The release behavior of ACV from the developed NPs exhibited an initial burst release within the first hour followed by a slower release (60% in 48 hrs).Egyptian Journal of Biomedical Sciences Vol. 23 (1) 2007: pp. 218-23

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and <i>ex vivo</i> skin permeation

<p><b>Objective:</b> The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience.</p> <p><b>Methods:</b> TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2²-level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (<i>Y</i>₁), vesicle size (<i>Y</i>₂), polydispersity index (<i>Y</i>₃), and zeta potential (<i>Y</i>₄) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug–excipient interactions, and vesicle stability were also investigated.</p> <p><b>Results:</b> The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (<i>p</i> < 0.01). The ethosomal vesicles were unilamellar with a nearly spherical shape. EPC-based ethosomes proved good stability.</p> <p><b>Conclusion:</b> The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.</p

Boosting the In Vivo Transdermal Bioavailability of Asenapine Maleate Using Novel Lavender Oil-Based Lipid Nanocapsules for Management of Schizophrenia

Lipid nanocapsules (LNCs) are promising for transdermal drug delivery due to their higher permeability-enhancing effects compared to polymeric nanoparticles. Lavender oil is an essential oil consisting of several terpenes (primarily linalool and linalyl acetate) known for their profound permeation-enhancing action. In the present work, we successfully encapsulated asenapine maleate (a second-generation antipsychotic that is highly metabolized by the liver, reducing its oral bioavailability) into biocompatible LNCs for transdermal application using a novel oily phase, i.e., lavender oil (LO-LNCs). A comparative study was conducted to determine the effects of different oily phases (i.e., Miglyol® 812, Labrafil® M1944CS, and Labrafac™ PG) on the LNCs. Surfactant types (Kolliphor® HS15, Kolliphor® EL and Tween80) and oil:surfactant ratios were studied. Blank and asenapine-loaded LNCs were optimized for particle size, polydispersity index, zeta potential, drug content and ex vivo skin permeation. Lavender oil and Labrafil® showed smaller vesicular sizes, while LO-LNCs increased the permeation of ASP across rat skin. In vivo pharmacokinetics revealed that LO-LNCs could increase the ASP Cmax via transdermal application by fourfold compared to oral suspension. They increased the bioavailability of ASP by up to 52% and provided sustained release for three days. The pharmacokinetic profile of the LO-LNCs was compared to ASP-loaded invasomes (discussed in a previous study) to emphasize LNCs’ transdermal delivery behavior

Microparticles-in-Thermoresponsive/Bioadhesive Hydrogels as a Novel Integrated Platform for Effective Intra-articular Delivery of Triamcinolone Acetonide

Intra-articular (IA) injection of thermo-responsive hydrogels coupled with microparticles (MPs) possess the benefit of sustaining the anti-inflammatory drug effect within the joint cavity for rheumatoid arthritis treatment. Star-shaped thermo-responsive poly(polyethylene glycol) methacrylate [Poly(PEGMA)] copolymers were synthesized using free radical polymerization technique and fully characterized. Triamcinolone acetonide (TA)-loaded PLA/mPEG-PDL MPs, previously optimized, were integrated into the synthesized copolymer solutions at various concentrations, and tested for their gelation temperatures. The MPs-in-hydrogel formulations were characterized using scanning electron microscope (SEM), viscosity measurements, ex-vivo bio-adhesion and in-vitro release studies. The anti-inflammatory effect of integrated systems was assessed in adjuvant-induced mono-arthritic rat knee joints, and compared to Kenacort® and TA-loaded MPs. Two copolymers were successfully synthesized; G-1 = poly(PEGMA188-ME-co-PEGMA475-ME) and G-2 = poly(PEGMA246-EE-co-PEGMA475-ME). Using tube inversion technique, the gel formation was found dependent on copolymer concentration. An irreversible aggregation was obtained at copolymer concentrations ≤ 10% (w/v), while a gel was formed at 20 and 30% (w/v) of both copolymers upon increasing temperature. The MP-hydrogel formulations were optimized at 20 and 30% (w/v) of G-1 and G-2 with gelation temperatures of 33 and 37 °C, respectively. SEM images revealed the porous microstructures of hydrogels and their adsorption on MP surfaces. The integrated formulae showed pseudoplastic behaviours, while bio-adhesion study confirmed their bio-adhesiveness on excised cartilage. In-vitro release study confirmed drug sustainment from MPs-hydrogels compared to MPs. In-vivo studies proved the superiority of MP-in-hydrogels in treatment of induced arthritis, relative to Kenacort® and MPs alone, suggesting the applicability of this integrated platform in IA drug delivery

Triamcinolone acetonide-loaded PLA/PEG-PDL microparticles for effective intra-articular delivery: synthesis, optimization, in vitro and in vivo evaluation

Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) in drug delivery is advantageous compared to polymers derived from fossil fuels. The present work aimed to produce microparticles (MPs) derived from novel sustainable polymers, loaded with triamcinolone acetonide (TA) for treatment of rheumatoid arthritis via intra-articular (IA) delivery. PDL was synthesized from green δ-decalactone monomers and co-polymerized with methoxy-polyethylene glycol (mPEG) forming PEG-PDL with different molecular weights. The Hansen's solubility parameters were applied to select the most compatible polymer with the drug. An o/w emulsion/solvent evaporation technique was used for MPs fabrication, using 3 [3] full factorial design. Selection of the optimized MPs was performed using Expert Design® software's desirability function. The optimized formulations were characterized using scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro release studies. The inhibition percents of inflammation and histopathological studies were assessed in complete Freund's adjuvant-induced rats' knee joints evaluating the effect of IA injections of selected MPs compared to the free drug suspension. Solubility studies revealed high compatibility and miscibility between TA and PEG-PDL1700, which was blended with PLA for convenient MPs formation. The in vitro characterization studies confirmed the formation of drug-copolymer co-crystals. The in vivo studies ensured the superiority of the newly designed composite MPs in inflammation suppression, compared to the free drug suspension and PLA MPs as well. The present study proved the advantage of using sustainable polymers in a novel combination for effective drug delivery and suggesting its usefulness in designing versatile platforms for therapeutic applications