Ragwa M. Farid

Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity.

Effect of sterilization on the physical stability of brimonidine-loaded solid lipid nanoparticles and nanostructured lipid carriers.

Nanoparticulate delivery systems have recently been under consideration for topical ophthalmic drug delivery. Brimonidine base-loaded solid lipid nanoparticles and nanostructured lipid carrier formulations were prepared using glyceryl monostearate as solid lipid and were evaluated for their physical stability following sterilization by autoclaving at 121°C for 15min. The objective of this work was to evaluate the effect of autoclaving on the physical appearance, particle size, polydispersity index, zeta potential, entrapment efficiency and particle morphology of the prepared formulations, compared to non-autoclaved ones. Results showed that, autoclaving at 121°C for 15min allowed the production of physically stable formulations in nanometric range, below 500nm suitable for ophthalmic application. Moreover, the autoclaved samples appeared to be superior to non-autoclaved ones, due to their increased zeta potential values, indicating a better physical stability. As well as, increased amount of brimonidine base entrapped in the tested formulations.

Gelucire-Based Nanoparticles for Curcumin Targeting to Oral Mucosa: Preparation, Characterization, and Antimicrobial Activity Assessment

The purpose of the study was to prepare and characterize curcumin (Cur) solid lipid nanoparticles (CurSLN) with a high-loading capacity and chemical stability for the treatment of oral mucosal infection. CurSLN were formulated using different lipids, namely, Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and poloxamer 407 as a surfactant. Formulae were evaluated for their entrapment efficiency, particle size, and ex vivo mucoadhesion test. Microbiological evaluation was carried out on six microorganisms, five of which are the most commonly affecting oral cavity in terms of determination of minimum inhibitory concentration (MIC), and minimum bactericidal concentration. Transmission electron microscopy was conducted for ultrathin section for Candida albicans-treated with formulated Cur. The results showed high entrapment efficiency and stability enhancement for Cur powder. Significant amount of Cur was retained onto the mucosal tissue indicating preferential mucosal uptake. CurSLN showed higher antimicrobial activity as compared with Cur raw material and chemically stabilized Cur where it showed MIC (0.185, 0.09375, 0.75, 3, 1.5, and 0.1875 mg/mL) against Staphylococcus aureus, Streptococcus mutans, Viridansstrept, Escherichia coli, Lactobacillus acidophilus, and Candida albicans, respectively. The prepared lipid nanoparticles maintained Cur chemical stability and microbiological activity. The lack of local antimicrobial therapeutics with minimum side effects augments the importance of studying natural products for this purpose.

Preparation, characterization and evaluation of novel elastic nano-sized niosomes (ethoniosomes) for ocular delivery of prednisolone

Abstract Niosomes embodying ethanol and minimum amount of cholesterol (ethoniosomes) could be promising ocular delivery systems for water soluble and insoluble drugs. This manuscript reports on novel nano-sized elastic niosomes (ethoniosomes) composed of Span 60: cholesterol (7:3 mol/mol) and ethanol, for ocular delivery of prednisolone acetate (Pred A) and prednisolone sodium phosphate (Pred P). These ethoniosomes were prepared with the thin film hydration (TFH) and ethanol injection (EI) methods, characterized for percentage entrapment efficiency (% EE), size, zeta potential, morphology, elasticity, in vitro release and physical stability. Ocular irritation, bioavailability and anti-inflammatory effects were evaluated and compared with the conventional suspension and solution eye drops. The prepared ethoniosomal vesicles (EV) had a Z-average diameter of 267 nm, zeta potential of approximately −40 mV and % change in size after extrusion of 4%. They were physically stable for at least 2 months at 4 °C. The prepared EV showed good ocular tolerability using the modified Draize’s test and the estimated relative ocular bioavailability for Pred A EV and Pred P EV was 1.54 and 1.75 times greater than that for the suspension and solution eye drops, respectively. The time required for complete healing from the clove oil-induced severe ocular inflammation was reduced to half with Pred A and Pred P EV. More interestingly, the intraocular pressure (IOP) elevation side effect recorded for Pred A and Pred P EV was significantly less than that for the conventional suspension and solution eye drops.

Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain

Abstract Objective: Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer’s disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Methods: Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Results: Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Conclusion: Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer’s disease management.

A new approach for treatment of precancerous lesions with curcumin solid-lipid nanoparticle-loaded gels: in vitro and clinical evaluation.

Abstract Objective: Preparation and characterization of curcumin solid–lipid nanoparticle (CurSLN)-loaded mucoadhesive gel for local treatment of oral precancerous lesions with low dose. Methodology: The formulated CurSLNs were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. Conventional mucoadhesive gel using binary system was adopted. The prepared gels were evaluated for in vitro drug dialysis, ex vivo mucoadhesion test and ex vivo permeation study using chicken buccal mucosa. Short-term clinical evaluation was carried out on 10 patients suffering oral erythroplakia in terms of pain index and lesion size measurement.1 Results: The results showed that the loaded gel with CurSLN showed good mucoadhesion property and 25 min in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated, however, significant amount of Cur was retained within the chicken buccal mucosal tissue confirmed by histological examination. Significant reduction in pain, and complete healing was observed after 6 weeks of treatment. Conclusion: The local use of Cur in low dose is a promising option for treatment of precancerous lesions. The lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

Nano-proniosomes enhancing the transdermal delivery of mefenamic acid.

Abstract Mefenamic acid (MA) is a BCS II class NSAID drug. It is available only in the form of tablets, capsules, and pediatric suspensions. Oral administration of MA is associated with severe gastrointestinal side effects. The aim of this study was to develop a convenient and low-cost transdermal drug delivery system for MA using proniosome as a novel carrier without the addition of penetration enhancers. The formulation factors, such as the presence of cholesterol, types of lecithin, and surfactants were investigated for their influence on the entrapment efficiency, rate of hydration, vesicle size, and zeta potential, in vitro drug release and skin permeation in order to optimize the proniosomal formulations with the minimum dose of the drug. Furthermore, the in vivo anti-inflammatory effect was evaluated on a formalin-induced rat paw edema model. The results showed that the type of surfactants had higher impact on the entrapment efficiency than the type of lecithins, with the highest in Span 80 (82.84%). The release of MA from Span 80 proniosomal gel was significantly affected by the type of lecithin used. The addition of cholesterol significantly increased both the drug release and the skin permeation flux of MA. Zeta potential showed a stable A4 noisomal suspension. DSC revealed the molecular dispersion of MA into the loaded proniosomes. In vivo study of the treatment group with MA proniosome gel showed a significant inhibition of rat paw edema compared with the same gel without the drug (control). The results of this study suggest that proniosomes are promising nano vesicular carriers and safe alternatives to enhance the transdermal delivery of MA.

Development of mucoadhesive microbeads using thiolated sodium alginate for intrapocket delivery of resveratrol

Resveratrol (Res), a polyphenolic phytoalexin, had shown a promising therapeutic efficacy towards treatment of periodontal disease in vitro. This work aims to develop Res microbeads with strong mucoadhesion using thiolated alginate (TA) for local treatment of periodontal pockets. TA was synthesized by conjugating sodium alginate (A) with thioglycolic acid. Product was evaluated by IR and DSC. Both A and A:TA Res microbeads with different ratios were prepared by ionotropic gelation method. Formulations were evaluated regarding their entrapment efficiency (%EE), swelling index (SI), in vitro drug release and kinetics. Selected formula was examined for its mucoadhesion by ex vivo wash-off method, surface morphology using scanning electron microscope (SEM) and stability against light. Clinical evaluation is running.Formation of TA was confirmed. %EE for all formulations ranged from 83.72 to 104.54%. Results revealed a significant lower SI for TA rich formulation (A/TA 1:1) along with slower release rate and zero-order kinetics, in addition to powerful mucoadhesion; 26% remaining of microbeads after 1h, compared to 2% for A microbeads. SEM micrographs showed a rough surface with drug precipitation. The formula maintained its %EE after 5h exposure to direct sunlight. A/TA 1:1 mucoadhesive Res microbeads could be exploited as a prolonged drug release devices for intrapocket application.

Osteogenic effect of locally applied Pentoxyfilline gel: in vitro and in vivo evaluations

Abstract The aim of this study was to formulate Pentoxyfylline drug (PTX) as a local bioadhesive Carbopol (Cbp) based gels for the aid of bone induction around an endosseus oral implant. The local delivery of the drug will probably avoid most of the problems associated with its systemic use including; disturbances in gastrointestinal tract and the central nervous system. Two concentrations of 1% and 3% Cbp containing 1% PTX were prepared. The gels were investigated for their physicochemical properties. Cbp based gels were found to be translucent with good homogeneity, uniform distribution of the drug and absence of any lumps. The pH of the gels was within neutrality, 7.1, which is considered to be acceptable to avoid the risk of any possible irritation in the oral cavity. The Cbp gels exhibited satisfactory bioadhesive properties and a pseudo-plastic rheological behavior. Cumulative drug released from the gels showed a controlled-release for more than 24 hours with the order of 3% >1% and the drug was released by diffusion mechanism from both gels. Statistical analysis revealed non-significant difference in drug content, rheological property and release rate of the stored gels for six months compared to the fresh ones. In vivo experimental results in rabbits have shown significant difference in bone depth induction of 3% and 1% Cbp gels with the formation of strong organized bone over the control group. Local administration of Pentoxifylline could be regarded as a valid approach in the management of osseointegration.

Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: future potential contribution in Alzheimer’s disease management

Abstract Purpose: Nasal galantamine hydrobromide (GH)/chitosan complex nanoparticles (CX-NP2) could have an improved therapeutic potential for managing Alzheimer’s disease (AD). The current study aimed to investigate if the complexation reaction between GH and chitosan altered the pharmacological and toxicological profiles of the parent drug; GH. Methods: The nasal administration of CX-NP2 to male Wistar rats for 12 consecutive days was compared to negative control group, and oral and nasal GH solutions treated groups in 3 mg/kg daily GH dose. Brain acetylcholinesterase (AChE) protein level and activity were assessed. The in vivo toxicity of CX-NP2 was evaluated via monitoring the clinical signs throughout the study. Histopathological examination of brain sections was performed. The intracellular localization of CX-NP2 within brain neurons was investigated using transmission electron microscopy. Results: GH/chitosan complexation did not negatively alter the pharmacological efficiency of GH. Intriguingly, nasal CX-NP2 exhibited a significant decrease of AChE protein level and activity in rat brains compared to the oral and nasal GH solutions. No toxicity signs or histopathological manifestations were noticed. The nanoparticles were found intracellularly in the brain neurons. Conclusion: The pharmacological efficacy and in vivo safety of nasal CX-NP2 confirm their promising potential to contribute to the management of AD intranasally.