Encapsulation of docetaxel in oily core polyester nanocapsules intended for breast cancer therapy

This study is designed to test the hypothesis that docetaxel [Doc] containing oily core nanocapsules [NCs] could be successfully prepared with a high percentage encapsulation efficiency [EE%] and high drug loading. The oily core NCs were generated according to the emulsion solvent diffusion method using neutral Labrafac CC and poly(d, l-lactide) [PLA] as oily core and shell, respectively. The engineered NCs were characterized for particle mean diameter, zeta potential, EE%, drug release kinetics, morphology, crystallinity, and cytotoxicity on the SUM 225 breast cancer cell line by dynamic light scattering, high performance liquid chromatography, electron microscopies, powder X-ray diffraction, and lactate dehydrogenase bioassay. Typically, the formation of Doc-loaded, oily core, polyester-based NCs was evidenced by spherical nanometric particles (115 to 582 nm) with a low polydispersity index (< 0.05), high EE% (65% to 93%), high drug loading (up to 68.3%), and a smooth surface. Powder X-ray diffraction analysis revealed that Doc was not present in a crystalline state because it was dissolved within the NCs' oily core and the PLA shell. The drug/polymer interaction has been indeed thermodynamically explained using the Flory-Huggins interaction parameters. Doc release kinetic data over 144 h fitted very well with the Higuchi model (R2 > 0.93), indicating that drug release occurred mainly by controlled diffusion. At the highest drug concentration (5 μM), the Doc-loaded oily core NCs (as a reservoir nanosystem) enhanced the native drug cytotoxicity. These data suggest that the oily core NCs are promising templates for controlled delivery of poorly water soluble chemotherapeutic agents, such as Doc

Current status of lectin-based cancer diagnosis and therapy

Lectins are carbohydrate recognizing proteins originating from diverse origins in nature, including animals, plants, viruses, bacteria and fungus. Due to their exceptional glycan recognition property, they have found many applications in analytical chemistry, biotechnology and surface chemistry. This manuscript explores the current use of lectins for cancer diagnosis and therapy. Moreover, novel drug delivery strategies aiming at improving lectin’s stability, reducing their undesired toxicity and controlling their non-specific binding interactions are discussed. We also explore the nanotechnology application of lectins for cancer targeting and imaging. Although many investigations are being conducted in the field of lectinology, there is still a limited clinical translation of the major findings reported due to lectins stability and toxicity concerns. Therefore, new investigations of safe and effective drug delivery system strategies for lectins are warranted in order to take full advantage of these proteins

Anti-HIV lectins and current delivery strategies

Lectins, a class of carbohydrate binding agents (CBAs), have been widely studied for their potential antiviral activity. In general, lectins exert their anti-HIV microbicidal activity by binding to viral envelope glycoproteins which hinders a proper interaction between the virus and its host, thereby preventing viral entry and replication processes. Several natural lectins extracted from plant, fungi, algae, bacteria and animals, as well as boronic acid-based synthetic lectins, have been investigated against the Human Immunodeficiency Virus (HIV). This manuscript discusses the nature of HIV envelope glycoprotein glycans and their implication in lectin antiviral activity for HIV/AIDS prevention. In addition, anti-HIV lectins and their carbohydrate specificity is reported. Furthermore, current formulations of anti-HIV lectins are presented to illustrate how to overcome delivery challenges. Although antiviral lectins will continue to occupy a major stage in future microbicide research, further investigation in this field should focus on novel delivery strategies and the clinical translation of CBAs

Modelling tenofovir release kinetics from hyaluronidase-sensitive nanomedicine: A deterministic approach

Despite being convenient and practical, current nanomedicine (NM) release kinetic model remain unscalable, non-specific and less descriptive of the underlying physicochemical determinants. However, a deterministic mathematical modelling could overcome these limitations. In this study, we develop a model, based on a system of two differential equations (accounting for NM degradation and then drug release from degraded NM), which enable us to estimate per capita rate constant α (#NP degraded/hr) and β (Drug Amount Release /NP), the net effect of the nanomedicine (NE factor ɣ= α.β) and the controlled release index (φ, ratio of drug release to NP degradation). The model analysis conducted with tenofovir loaded hyaluronidase sensitive NM clearly shows the α factor significantly increased with triggering stimuli due to its enzymatic action on its substrate (hyaluronic acid). However, the β factor remained relatively unchanged, due to intrinsic physicochemical properties of the drug as limiting factor. The application of the ratio of NE factor analysis clearly enabled us to effectively screen among various nanoformulations and identified the best hyaluronidase-sensitive NM formulation, exhibiting the highest ratio (3.7-fold increase compared to no enzyme). The φ value confirmed the controlled release and stimuli sensitivity of the nanosystem. Moreover, the computed drug release rate (dM/dt) is consistent with other existing mathematical models (under valid assumption). The key advantages of this approach are i) relevancy to underlying physicochemical and biochemical process, ii) versatility and application to various NM kinetics, and iii) prediction of temporo-spatial distribution of the drug loaded nanocarrier (NC) that could potentially improve vitro/in vivo correlation study. This unique approach is applicable for a more specific and more meaningful/physicochemically relevant description of bioactive agent release from NM or NC for various applications

Formulation of spray-dried phenytoin loaded poly(epsilon-caprolactone) microcarrier intended for brain delivery to treat epilepsy

This study evaluates the efficacy of the spray-drying technique in the bioengineering of phenytoin (PHT) containing poly(-caprolactone) (PCL) microcarrier intended for brain delivery for long-term treatment of epilepsy. Through orthogonally designed experiments, the optimal formulation and process variables for the preparation of PCL-microcarriers containing PHT were obtained. The produced microcarriers were characterized by coulter counter, scanning electron, scanning transmission electron microscopies, differential scanning calorimetry, powder X-ray diffraction, and in vitro release. The results showed that the produced microcarriers have a spherical structure, uniform size distribution, and a particle mean diameter of about 4.0 µm, which is suitable for brain delivery. The PHT was loaded as dispersed microcrystals within the PCL-microcarriers. From this system, PHT was released slowly into a buffer solution for approximately 14 days without any burst effect. These data suggested that PHT containing spray-dried PCL-microcarrier may be a promising drug delivery system for local brain delivery and long-term treatment of pharmacoresistant epilepsy. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1018-1030, 200

Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: <i>In Vitro</i> and <i>in Vivo</i> Evaluations

It is hypothesized that thiolated chitosan (TCS) core/shell nanofibers (NFs) can enhance the drug loading of tenofovir, a model low molecular weight and highly water-soluble drug molecule, and improve its mucoadhesivity and <i>in vivo</i> safety. To test this hypothesis, poly­(ethylene oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analyzed using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and <i>Lactobacilli crispatus</i>, fluorescence imaging and periodic acid colorimetric method, respectively. <i>In vivo</i> safety studies are performed in C57BL/6 mice followed by H&E and immunohistochemical (CD45) staining analysis of genital tract. The mean diameters of PEO, PEO/TCS, and PEO/TCS-PLA NFs are 118.56, 9.95, and 99.53 nm, respectively. The NFs exhibit smooth surface. The drug loading (13%–25%, w/w) increased by 10-fold compared to a nanoparticle formulation due to the application of the electrospinning technique. The NFs are noncytotoxic at the concentration of 1 mg/mL. The PEO/TCS-PLA core/shell NFs mostly exhibit a release kinetic following Weibull model (<i>r</i>² = 0.9914), indicating the drug release from a matrix system. The core/shell NFs are 40–60-fold more bioadhesive than the pure PEO based NFs. The NFs are nontoxic and noninflammatory <i>in vivo</i> after daily treatment for up to 7 days. Owing to their enhanced drug loading and preliminary safety profile, the TCS core/shell NFs are promising candidates for the topical delivery of HIV/AIDS microbicides such as tenofovir