Effect of Autoclaving on the Physicochemical Properties and Biological Activity of Aluminum Oxyhydroxide Used as an Adjuvant in Vaccines.

The long-term biodistribution of non-biodegradable microstructures or nanostructures used in vaccinations is widely unknown. This is the case for aluminum oxyhydroxide, the most widely used vaccine adjuvant, which is a nanocrystalline compound that spontaneously forms nanoprecipitates. Although generally well-tolerated, aluminum oxyhydroxide is detected in macrophages a long time after vaccination in individuals predisposed to the development of systemic and neurological aspects of the autoimmune (inflammatory) syndrome induced by modified adjuvant. In the present study, we established that the terminal sterilization of aluminum oxyhydroxide by autoclaving in final container vials produced measurable changes in its physicochemical properties. Moreover, we found that these changes included (1) a decreasing in the pH of aluminum oxyhydroxide solutions, (2) a reduction in the adsorption capacity of bovine serum albumin, (3) a shift in the angle of X-ray diffraction, (4) a reduction in the lattice spacing, causing the crystallization and biopersistence of modified aluminum oxyhydroxide in the macrophage, as well as in muscle and the brain.

The Use of Cyclodextrin or its Complexes as a Potential Treatment Against the 2019 Novel Coronavirus: A Mini-Review.

Severe Acute Respiratory Syndrome Coronavirus 2 has spread rapidly since its discovery in December 2019 in the Chinese province of Hubei, reaching this day all the continents. This scourge is, unfortunately, in lineage with various dangerous outbreaks such as Ebola, Cholera, Spanish flu, American seasonal flu. Until today, the best solution for the moment remains prevention (Social distancing, hand disinfection, use of masks, partial or total sanitary containment, etc.); there is also the emergence of drug treatment (research and development, clinical trials, use on patients). Recent reviews emphasized the role of membrane lipids in the infectivity mechanism of SARS-COV-2. Cholesterol-rich parts of cell membranes serve as docking places of host cells for the viruses. Coronavirus 2 is a member of a virus family with lipid envelope that fuses with host cell through endocytosis, internalizing its components in the cell. In vitro cell models have shown that depletion of cholesterol by cyclodextrin, and particularly methyl beta cyclodextrin disturb the host cell membrane lipid composition this way, reducing the attachment of the virus to the protein receptors. This review aims to summarize the state of the art of research concerning the use of cyclodextrin or its complexes as a potential treatment against this new virus and update work already published.

New Formulation and Evaluation of Camptothecin Encapsulated and/or Dispersed Suppository.

BACKGROUND: Camptothecin is known for its potent anticancer activity. However, its optimal activity is reduced due to its low solubility and stability in biological media. OBJECTIVE: The aim of the present study is to design and characterize a Camptothecin (CPT) suppository formulation. METHODS: Rectal suppositories of camptothecin alone, encapsulated with Cyclodextrin (CD) and in the ternary system (CPT encapsulated with cyclodextrin and dispersed in Polyethylene Glycol (PEG) 6000) were prepared using various hydrophobic and hydrophilic polymeric bases as semi-synthetic glyceride (Suppocire® AM Pellets) and Polyethylene Glycols (PEGs) mixtures. Formulations were evaluated by various parameters like weight variation, drug content, hardness and liquefaction time. In vitro release study was performed in USP type I apparatus using phosphate buffer pH 7.2 as dissolution media. RESULTS: Suppositories were within the permissible range of all physical parameters. In vitro drug released from water soluble base (PEG) was greater than that from oil soluble base with ninety percent (90%) of drug dissolution. It was also established that drug release from various formulations was by diffusion mechanism, according to the Higuchi's equation. CONCLUSION: This new formulation offers a new approach to colorectal cancer treatment by offering an alternative and simple drug administration route.

Development and validation of HPLC method for simultaneous quantification of alpha-tocopherol (free or encapsulated) and cholesterol in semen cryopreservation media.

The HPLC method was developed and validated for assaying alpha-tocopherol and cholesterol in cryopreservation media. Chromatographic separation was performed on an isocratic system, using a C-18 column. The mobile phase was composed of a mixture of methanol:acetonitrile:water 68:28:4 (v/v/v), using a flow rate of 1.5 mL/min and 20 µL injection volume, at a wavelength of 208 nm. The method was validated according to International Conference on Harmonization guidelines. The method proved to be specific, accurate, precise, and linear with correlation coefficients greater than 0.996 over a wide concentration range of both analytes. Vitamin E and cholesterol presented limits of detection of 0.002 mg/mL, 0.026 mg/mL and limits of quantitation of 0.006 mg/mL, 0.086 mg/mL, respectively. This method is simple and rapid, shows high precision and accuracy, and offers the advantage of simultaneous assaying of vitamin E and cholesterol (alone, in cyclodextrins complexes or in liposome loaded) on semen cryopreservation media.

Amorphous solid dispersion studies of camptothecin-cyclodextrin inclusion complexes in PEG 6000.

Abstract: The present work focused on the solubility enhancement of the poorly water-soluble anti-cancer agent camptothecin which, in its natural state, presents poor solubility inducing lack of activity with a marked toxicity. A new approach is adopted by using a ternary system including camptothecin (CPT) and cyclodextrins (CDs) dispersed in polyethylene glycol (PEG) 6000. Camptothecin solubility variations in the presence of α-CD, ß-CD, γ-CD, hydroxypropyl-α-CD (HPα-CD), hydroxypropyl-ß-CD (HPß-CD), permethyl-ß-CD (PMß-CD) and sulfobutyl ether-ß-CD (SBEß-CD), were evaluated by Higuchi solubility experiments. In the second part, the most efficient camptothecin/P-CDs binary systems, mainly HPß-CD and PMß-CD, were dispersed in PEG 6000. In addition to a drug release and modeling evaluation, the CPT interactions with CDs and PEG 6000 to prepared the amorphous solid dispersion in the binary and ternary systems were investigated by Fourier transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analyses (TGA) and X-ray powder diffraction (XRPD). The results showed that HPß-CD and PMß-CD were the most efficient for camptothecin solubilization with highest apparent equilibrium constants. Dissolution studies showed that percentage of CPT alone after two hour in 0.1 M HCI medium, did not exceed 16%, whereas under the same conditions, CPT/PMß-CD complex reached 76%. When dispersing the binary systems CPT/ß-CDs in PEG 6000, the velocity and the percentage of CPT release were considerably improved whatever the CD used, reaching the same value of 85%. The binary and ternary systems characterization demonstrated that CPT inclused into the CDs cavity, replacing the water molecules. Furthermore, a drug transition from crystalline to amorphous form was obtained when solid dispersion is realized. The present work demonstrated that ternary complexes are promising systems for CPT encapsulation, and offer opportunities to use non toxic and commonly solubilizing carriers: ßCD and PEG 6000 to improve bioavailability.