Maha Nasr

Vesicular aceclofenac systems: A comparative study between liposomes and niosomes

Vesicular delivery systems have been reported to serve as local depot for sustained drug release. Aceclofenac multilamellar liposomes and niosomes were prepared and a comparative study was done between them through evaluation of entrapment efficiency, particle size, shape, differential scanning calorimetry and in vitro drug release. A stability study was carried out by investigating the leakage of aceclofenac and the change in the vesicles particle size when stored at (2–8°C) for 3 months. The anti-inflammatory effect of aceclofenac vesicles was assessed by the rat paw oedema technique. Results showed that the entrapment efficiency and the in vitro release of aceclofenac from the vesicles can be manipulated by varying the cholesterol content, the type of surfactant as well as the type of charge. Niosomes showed better stability than liposomes. Both vesicular systems showed significant sustained anti-inflammatory activity compared to the marketed product, with niosomes being superior to liposomes as manifested by both oedema rate and inhibition rate percentages suggesting their effectiveness as topical anti-inflammatory delivery systems.

Transdermal delivery of betahistine hydrochloride using microemulsions: physical characterization, biophysical assessment, confocal imaging and permeation studies.

Transdermal delivery of betahistine hydrochloride encapsulated in various ethyl oleate, Capryol 90(®), Transcutol(®) and water microemulsion formulations was studied. Two different kinds of phase diagrams were constructed for the investigated microemulsion system. Pseudoplastic flow that is preferable for skin delivery was recorded for the investigated microemulsions. A balanced and bicontinuous microemulsion formulation was suggested and showed the highest permeation flux (0.50±0.030mgcm(-2)h(-1)). The effect of the investigated microemulsions on the skin electrical resistance was used to explain the high permeation fluxes obtained. Confocal laser scanning microscopy was used to confirm the permeation enhancement and to reveal the penetration pathways. The results obtained suggest that the proposed microemulsion system highlighted in the current work can serve as a promising alternative delivery means for betahistine hydrochloride.

Amphotericin B lipid nanoemulsion aerosols for targeting peripheral respiratory airways via nebulization.

Amphotericin B (AmB) lipid nanoemulsions were prepared and characterized and their suitability for pulmonary delivery via nebulization was evaluated. AmB nanoemulsions were prepared by sonicating and vortexing the drug with two commercially available lipid nanoemulsions: the Intralipid(®) or Clinoleic(®). Loading the nanoemulsions with the drug slightly increased the size of the lipid droplets and did not affect the zeta potential of the nanoemulsions. The loading efficiency of AmB was found to be 87.46±2.21% in the Intralipid(®) nanoemulsions and 80.7±0.70% in the Clinoleic(®) formulation. This respectively corresponded to 21.86 mg and 20.19 mg of AmB being successfully loaded in the nanoemulsions. On aerosolization using a Pari Sprint jet nebulizer, both nanoemulsions produced very high drug output which was approximately 90% for both formulations. Using the two-stage impinger, the Clinoleic(®) emulsion had higher fine particle fraction (FPF) than the Intralipid(®), since the Clinoleic(®) displayed higher deposition of AmB in the lower impinger stage (exceeding 80%), compared to 57% for the Intralipid(®). Overall, the ease of preparation of the AmB lipid nanoemulsions, along with their in vitro nebulization performance suggest that lipid nanoemulsions could be successful nanocarriers for delivery of AmB to the peripheral respiratory airways.

Recent advances in topical formulation carriers of antifungal agents.

Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. Examples of these newer carriers include micelles, lipidic systems such as solid lipid nanoparticles and nanostructured lipid carriers, microemulsions and vesicular systems such as liposomes, niosomes, transfersomes, ethosomes, and penetration enhancer vesicles.

Suitability of liposomal carriers for systemic delivery of risedronate using the pulmonary route

Abstract Objective: This study aims at testing the hypothesis that reversed phase evaporation liposomes (REVs) are suitable for systemic delivery of an anti-osteporotic drug (risedronate sodium (RS)) via pulmonary nebulization. Materials and methods: RS REVs were prepared using phospholipids and cholesterol with or without stearylamine, and were characterized for morphology, entrapment efficiency (EE%), in vitro release, particle size and aerosolization behavior from an actively vibrating mesh nebulizer. RS accumulation in rat bones following intra-tracheal administration of the selected formulation was assessed using a radiolabelling-based technique, and histological examination of rat lung tissue was performed to assess its safety. Results: The EE% of RS REVs ranged from 8.8% to 58.96% depending on cholesterol molar ratio, phospholipid type and presence of stearylamine. RS REVs’ particle size ranged from 2.15 to 3.61 µm and were spherical and moderately polydisperse. Nebulization of the selected formulation showed an aerosol output of 85%, a fine particle fraction of 70.75% and a predicted alveolar deposition of 30.39%. The amount of radiolabelled RS deposited in rat bones after pulmonary administration was 20%, while being considerably safe on lung tissues. Conclusion: Cationic REVs is a promising carrier for systemic delivery of RS for treatment of bone resorptive diseases.

Different modalities of NaCl osmogen in biodegradable microspheres for bone deposition of risedronate sodium by alveolar targeting

Risedronate sodium was formulated into polylactide-co-glycolic acid microspheres for pulmonary delivery using the w/o/w double emulsion technique. Sodium chloride was used as osmogen in either the internal or external aqueous phase to surface-engineer the particles to achieve favorable properties. The prepared microspheres were characterized for the surface morphology, entrapment efficiency, in vitro release behavior, particle size, surface area, aerodynamic as well as powder flow properties. Furthermore, the safety of the drug and the selected formula were assessed by MTT viability test performed on Calu-3 cell line as well as histopathological lung tissue examination. A novel in vivo approach based on the radiolabeling of risedronate sodium with I(125) was developed in order to assess its deposition in the bones of male albino rats. The majority of the prepared microspheres exhibited high entrapment efficiency, sustained release profile up to 15 days, suitable geometric and aerodynamic particle sizes as well as good flow properties. The safety of the drug and the selected formula were proven by the high cell viability percentage of Calu-3 cells as well as the normal lung histology after intra-tracheal administration. The in vivo study showed high bone deposition for risedronate sodium following the pulmonary route, suggesting that it could be utilized as an alternative route of administration for delivery of bisphosphonates.

Topical colloidal indocyanine green-mediated photodynamic therapy for treatment of basal cell carcinoma

Abstract Indocyanine green (ICG) is a near-IR fluorescent dye with a great potential for application as photosensitizer in topical photodynamic therapy (PDT) of skin diseases. Despite its merits, its use has been hampered by its high degradation rate. Therefore, in the current article, ICG was encapsulated in a vesicular colloidal nanocarrier (transfersomes), with the aim of enhancing its therapeutic efficacy. Transfersomes were characterized for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release and histopathological effect on mice skin. A pilot clinical study was conducted to test its therapeutic potential for PDT of basal cell carcinoma (BCC). Transfersomal ICG displayed particle size (∼125 nm) and a negative zeta potential (∼−31 mV). Transfersomes were also able to sustain the release of ICG >2 h. Upon incorporation of transfersomal ICG in gel form, it was found to maintain the normal histology of mice skin post-irradiation with diode laser 820 nm. Moreover, ICG transfersomal PDT achieved 80% clearance rate for BCC patients with minimal pain reported during treatment. The previous findings suggest that transfersomal nanoencapsulated ICG is a promising treatment modality for BCC.

Cancer nanotheranostics: A review of the role of conjugated ligands for overexpressed receptors

Abstract Cancer treatment using chemotherapy has many drawbacks because of its non‐specificity, in which the chemotherapeutic agent attacks both normal and cancerous cells, leading to severe damage to the normal cells, especially rapidly proliferating ones. Cancer targeting enables the drug to kill only tumor cells without adversely affecting healthy tissues, which leads to the improvement of the patients well‐being. Nanoparticles offer several advantages in drug delivery such as enhancing the solubility of hydrophobic drugs, sustaining their release and prolonging their circulation time. The ability of nanoparticles to specifically target tumor cells makes them a useful delivery system for anticancer agents. The type of the delivery system and formulation additives used can also improve the delivery of the anticancer agent. This review highlights some of the most highly sought receptors to be targeted in selective cancer treatment. It also reports some of the recent advances in cancer targeting using drug‐loaded ligand‐conjugated nanocarriers. Graphical abstract Figure. No Caption available.

Lipid based Nanocapsules: A Multitude of Biomedical Applications

Lipid nanocapsules with their unique composition represent a promising biocompatible drug delivery platform in nanometer range with narrow size distribution. They are highly stable in comparison to other nano-vectors and were found to impart very desirable characteristics to the therapeutic molecule being delivered within. The current review sheds the light on the methods of preparation of lipid nanocapsules, which are simple and easily scalable, in addition to providing examples of post insertion of some compounds for prolonging vascular circulation, protection, and targeting several diseases. In addition, the review discusses the vast in vitro and in vivo applications of lipid nanocapsules when administered via different routes such as oral, parenteral and transdermal routes. Promising use of nanocapsules in treatment of cancer, Alzheimers disease, dermatological conditions and other miscellaneous applications are highlighted.

Optimizing the dermal accumulation of a tazarotene microemulsion using skin deposition modeling

Abstract Context: It is well known that microemulsions are mainly utilized for their transdermal rather than their dermal drug delivery potential due to their low viscosity, and the presence of penetration enhancing surfactants and co-surfactants. Objective: Applying quality by design (QbD) principles, a tazarotene microemulsion formulation for local skin delivery was optimized by creating a control space. Materials and methods: Critical formulation factors (CFF) were oil, surfactant/co-surfactant (SAA/CoS), and water percentages. Critical quality attributes (CQA) were globular size, microemulsion viscosity, tazarotene skin deposition, permeation, and local accumulation efficiency index. Results and discussion: Increasing oil percentage increased globular size, while the opposite occurred regarding SAA/CoS, (p = 0.001). Microemulsion viscosity was reduced by increasing oil and water percentages (p < 0.05), due to the inherent high viscosity of the utilized SAA/CoS. Drug deposition in the skin was reduced by increasing SAA/CoS due to the increased hydrophilicity and viscosity of the system, but increased by increasing water due to hydration effect (p = 0.009). Models with very good fit were generated, predicting the effect of CFF on globular size, microemulsion viscosity, and drug deposition. A combination of 40% oil and 45% SAA/CoS showed the maximum drug deposition of 75.1%. Clinical skin irritation study showed that the aforementioned formula was safe for topical use. Conclusion: This article suggests that applying QbD tools such as experimental design is an efficient tool for drug product design.