Polycaprolactone and polycaprolactone triol blends to obtain a stable liquid nanotechnological formulation: synthesis, characterization and in vitro - in vivo taste masking evaluation.

The use of polymeric blends is a potential strategy to obtain novel nanotechnological formulations aiming at drug delivery systems. Saquinavir, an antiretroviral drug, was chosen as a model drug for the development of new stable liquid formulations with unpleasant taste masking properties. Three formulations containing different polymeric ratios (1:3, 1:1 and 3:1) were prepared and properly characterized by particle size distribution, zeta potential, pH, drug content and encapsulation efficiency measurements. The stability was verified by monitoring the zeta potential, particle size distribution, polydispersity index and drug content by 90 days. The light backscattering analysis was used to early identify possible phenomena of instability in the formulations. The in vitro drug release and saquinavir cytotoxicity were evaluated. The in vitro and in vivo taste masking properties were studied using an electronic tongue and a human sensory panel. All formulations presented nanometric sizes around 200 nm and encapsulation efficiency above 99%. The parameters evaluated for stability remained constant throughout 90 days. The in vitro tests showed a controlled drug release and absence of toxic effects on human T lymphocytes. The electronic tongue experiment showed taste differences for all formulations in comparison to drug solutions, with a more pronounced difference for the formulation with higher polycaprolactone content (3:1). This formulation was chosen for in vivo sensory panel evaluation which results corroborated the electronic tongue experiments. In conclusion, the polymer blend nanoformulation developed herein showed the promising application to incorporate drugs aiming at pharmaceutical taste-masking properties.

Production of Isotonic, Sterile, and Kinetically Stable Lipid-Core Nanocapsules for Injectable Administration.

Lipid-core nanocapsules (LNC) were designed and prepared as a colloidal system for drug targeting to improve the stability of drugs and allow their controlled release. For parenteral administration, it is necessary to ensure formulation sterility. However, sterilization of nanotechnological devices using an appropriate technique that keeps the supramolecular structure intact remains a challenge. This work aimed to evaluate the effect of autoclaving on the physicochemical characteristics of LNC. Formulations were prepared by the self-assembling method, followed by isotonization and sterilization at varying times and temperatures. The isotonicity was confirmed by determining the freezing temperature, which was -0.51°C. The formulation was broadly characterized, and the diameter of the particles was determined utilizing complementary methods. To evaluate the chemical stability of poly(ε-caprolactone), its molecular weight was determined by size exclusion chromatography. The physicochemical characteristics (average diameter, viscosity, and physical stability) of the formulation were similar before and after adding glycerol and conducting the sterilization at the highest temperature (134°C) and the shorter exposure time (10 min). After autoclaving, the sterility test was performed and showed no detectable microbial growth. Multiple light scattering demonstrated that the formulations were kinetically stable, and the mean diameter was constant for 6 months, corroborating this result. The polymer was chemically stable in the sterilized formulation. Isotonic and sterile LNC aqueous suspensions were produced using glycerol and autoclaving. Briefly, the results open an opportunity to produce an isotonic and sterile LNC aqueous dispersion applicable as nanomedicine for intravenous administration in clinical trials.

Nanoencapsulation of Rose-Hip Oil Prevents Oil Oxidation and Allows Obtainment of Gel and Film Topical Formulations.

The rose-hip oil holds skin regenerating properties with applications in the dermatological and cosmetic area. Its nanoencapsulation might favor the oil stability and its incorporation into hydrophilic formulations, besides increasing the contact with the skin and prolonging its effect. The aim of the present investigation was to develop suitable rose-hip-oil-loaded nanocapsules, to verify the nanocapsule effect on the UV-induced oxidation of the oil and to obtain topical formulations by the incorporation of the nanocapsules into chitosan gel and film. The rose-hip oil (500 or 600 µL), polymer (Eudragit RS100®, 100 or 200 mg), and acetone (50 or 100 mL) contents were separately varied aiming to obtain an adequate size distribution. The results led to a combination of the factors acetone and oil. The developed formulation showed average diameter of 158 ± 6 nm with low polydispersity, pH of 5.8 ± 0.9, zeta potential of +9.8 ± 1.5 mV, rose-hip oil content of 54 ± 1 µL/mL and tendency to reversible creaming. No differences were observed in the nanocapsules properties after storage. The nanoencapsulation of rose-hip oil decreased the UVA and UVC oxidation of the oil. The chitosan gel and film containing rose-hip-oil-loaded nanocapsules showed suitable properties for cutaneous use. In conclusion, it was possible to successfully obtain rose-hip-oil-loaded nanocapsules and to confirm the nanocapsules effect in protecting the oil from the UV rays. The chitosan gel and film were considered interesting alternatives for incorporating the nanoencapsulated rose-hip oil, combining the advantages of the nanoparticles to the advantages of chitosan.

Applying the sensory analysis in the development of chitosan hydrogel containing polymeric nanocapsules for cutaneous use.

This work aimed to develop a chitosan hydrogel containing polymeric nanocapsules with optimized sensory properties, linking the advantages of the nanocarriers, such as controlled release and protection of the substances, to the chitosan properties, such as bioadherence, cicatrizing effect, and antimicrobial activity. Sixty untrained volunteers evaluated the sensory properties of chitosan hydrogels compared to hydroxyethyl cellulose gels (Phase I) and to optimized chitosan gels (Phase II). The volunteers' preference between formulations was also evaluated. The chitosan hydrogel, despite the presence of nanocapsules, presented higher immediate stickiness and film formation on the skin, and lower acceptance than the hydroxyethyl cellulose gels. Regarding the optimized gel, decrease on the film formation and increase on the homogeneity of the film was observed, compared to the prior chitosan gel. So, the optimization of the chitosan gel led to higher acceptance by the volunteers. The presence of nanocapsules, besides increasing the chitosan gel consistence, increased the perception of film formation. For the optimized chitosan gel, the nanocapsules increased the homogeneity of the film formed on the skin, without increasing the perception of film formation. In conclusion, through sensory analysis, the formulation was optimized presenting, at the final stage, adequate sensory properties for cutaneous use.

Lamivudine and Zidovudine-Loaded Nanostructures: Green Chemistry Preparation for Pediatric Oral Administration.

Here, we report on the development of lipid-based nanostructures containing zidovudine (1 mg/mL) and lamivudine (0.5 mg/mL) for oral administration in the pediatric population, eliminating the use of organic solvents, which is in accordance with green chemistry principles. The formulations were obtained by ultrasonication using monoolein (MN) or phytantriol (PN), which presented narrow size distributions with similar mean particle sizes (~150 nm) determined by laser diffraction. The zeta potential and the pH values of the formulations were around -4.0 mV and 6.0, respectively. MN presented a slightly higher incorporation rate compared to PN. Nanoemulsions were obtained when using monoolein, while cubosomes were obtained when using phytantriol, as confirmed by Small-Angle X-ray Scattering. The formulations enabled drug release control and protection against acid degradation. The drug incorporation was effective and the analyses using an electronic tongue indicated a difference in palatability between the nanotechnological samples in comparison with the drug solutions. In conclusion, PN was considered to have the strongest potential as a novel oral formulation for pediatric HIV treatment.

Development and stability of innovative semisolid formulations containing nanoencapsulated lipoic acid for topical use.

INTRODUCTION: The cosmetic benefit obtained from the use of lipoic acid in the treatment of different skin disorders related to oxidative stress is compromised by its chemical instability, which complicates the preparation of cosmetic formulations suitable for topical use. Considering that nanoencapsulation increases the stability of lipoic acid, the aim of this study was to develop different semisolid formulations, based on innovative cosmetic ingredients and containing lipoic acid-loaded nanocapsules. MATERIALS AND METHODS: Lipoic acid-loaded nanocapsules (5.0 mg/mL) were prepared by interfacial deposition of the pre-formed polymer and the thickening agents Aristoflex AVC and DC RM2051, used alone or in combination. The formulations were characterized in terms of resistance to centrifugation, pH, lipoic acid content, rheological characteristics and optical parameters determined by multiple light scattering. Also, their stability when subjected to cycles of thermal heating and freezing was evaluated. RESULTS AND DISCUSSION: The semisolid formulations presented suitable properties for cutaneous administration, with enhanced physicochemical stability, considering the drug content and resistance to centrifugation, being observed for the formulations containing nanocapsules. All of the proposed formulations showed pseudoplastic flow behavior. The nanoencapsulation leads to an increase in the flow indexes. After the stress cycles an improvement in the consistency, particularly for the formulations containing nanocapsules, was observed. According to the results of multiple light scattering analysis, the formulations can be considered stable. CONCLUSIONS: The use of new cosmetic ingredients, unlike traditional hydrogels, represents a differentiated platform for preparation of stable semisolid formulations containing polymeric nanocapsules, presenting physicochemical properties suitable for topical use.