Enhancement of the Mechanical and Drug-Releasing Properties of Poloxamer 407 Hydrogels with Casein.

PURPOSE: Topical therapy of local disease (e.g. skin) is advantageous over oral therapy since there is less systemic drug distribution (so fewer side-effects), no first-pass effect, etc. However, patient compliance with topical therapy can be poor as it may require many applications a day and can last months. Here we propose a topical controlled release formulation with thermoresponsive gelation at body temperature and improved adhesiveness, making it easier to remain in contact with the body. METHODS: The formulation contains two excipients, poloxamer 407 (P407) and casein. Casein can modify the properties of the hydrogel through molecular entanglement. In addition, tissue reaction and drug release profile were evaluated. RESULTS: Changes in casein concentration affected adhesive strength, viscosity, mechanical properties and drug release, presumably by hydrophobic interactions between casein and P407. Two different concentrations of P407 were tested with two different concentrations of casein. Formulations containing 5% and 10% casein released 80% of model drug in 48 h, while formulations without casein released the same fraction in around 24 h hours. Formulations with 10% casein had almost twice the adhesive strength of those without casein. CONCLUSIONS: Addition of casein modified the mechanical properties and drug release rate of the hydrogel. There was no inflammation or injury after brief exposure in vivo.

Bromelain Loading and Release from a Hydrogel Formulated Using Alginate and Arabic Gum.

An ideal wound dressing ensures a moist environment around the wound area and absorbs exudates from the wound surface. Topical application of bromelain to incised wounds has been shown to reprogram the wound microenvironment to promote effective tissue repair. Combining the characteristics of hydrogels and bromelain is therefore of great interest. Herein, we describe the development of a hydrogel, formulated using alginate and Arabic gum, for bromelain loading and release. The hydrogel formulation was evaluated using response surface methodology, considering the pH value and the concentration of alginate and Arabic gum. Bromelain loading and release were evaluated based on passive diffusion. Differential scanning calorimetry and Fourier transform infrared spectroscopy were performed to confirm bromelain immobilization in the hydrogel. The final hydrogel formulation had a swelling ratio of 227 % and incorporated 19 % of bromelain from a bromelain solution. Bromelain immobilization in the hydrogel was the result of hydrogen bond formation and was optimal at 4 °C after 4 h of contact. This evidence suggests that bromelain entrapment into a hydrogel is a promising strategy for the development of wound dressings that support the debridement of burns and wounds.

Bacterial nanocellulose production and application: a 10-year overview.

Production of bacterial nanocellulose (BNC) is becoming increasingly popular owing to its environmentally friendly properties. Based on this benefit of BNC production, researchers have also begun to examine the capacity for cellulose production through microbial hosts. Indeed, several research groups have developed processes for BNC production, and many studies have been published to date, with the goal of developing methods for large-scale production. During BNC bioproduction, the culture medium represents approximately 30 % of the total cost. Therefore, one important and challenging aspect of the fermentation process is identification of a new cost-effective culture medium that can facilitate the production of high yields within short periods of time, thereby improving BNC production and permitting application of BNC in the biotechnological, medical, pharmaceutical, and food industries. In this review, we addressed different aspects of BNC production, including types of fermentation processes and culture media, with the aim of demonstrating the importance of these parameters.

Alginate-amphotericin B nanocomplexes covered by nanocrystals from bacterial cellulose: physico-chemical characterization and in vitro toxicity.

Nanocomplexes systems made up natural poylymers have pharmacotechnical advantages such as increase of water solubility and a decrease of drugs toxicity. Amphotericin B (AmB) is a drug apply as anti-leishmanial and anti-fungal, however it has low water solubility and high toxicity, limiting its therapeutic application. With this in mind, the present study aimed to produce nanocomplexes composed by alginate (Alg), a natural polymer, with AmB covered by nanocrystals from bacterial cellulose (CNC). For this reason, the nanocomplexes were produced utilizing sodium alginate, amphotericin B in a borate buffer (pH 11.0). The CNC was obtained by enzymatic hydrolysis of the bacterial cellulose. To CNC cover the nanocomplexes 1 ml of the nanocomplexes was added into 1 ml of 0.01% CNC suspension. The results showed an ionic adsorption of the CNC into the Alg-AmB nanocomplexes surface. This phenomena was confirmed by an increase in the particle size and PDI decrease. Besides, nanocomplexes samples covered by CNC showed uniformity. The amorphous inclusion of AmB complex into the polysaccharide chain network in both formulations. AmB in the nanocomplexes was in supper-aggregated form and showed good biocompatibility, being significantly less cytotoxic in vitro against kidney cells and significantly less hemolytic compared to the free-drug. The in vitro toxicity results indicated the Alg-AmB nanocomplexes can be considered a non-toxic alternative to improve the AmB therapeutic effect. All process to obtain nanocomplexes and it coat was conduce without organic solvents, can be considered a green process, and allowed to obtain water soluble particles. Furthermore, CNC covering the nanocomplexes brought additional protection to the system can contribut advancement in the pharmaceutical.

PVA/anionic collagen membranes as drug carriers of ciprofloxacin hydrochloride with sustained antibacterial activity and potential use in the treatment of ulcerative keratitis.

Devices such as contact lenses and collagen shields have been used to improve the antibiotic bioavailability of eye drops formulations in the treatment of ulcerative keratitis. Nevertheless, these devices are not sustained drug delivery systems, and a combination with eye drops is necessary. In animal patients, it requires constant supervision by trained personnel to avoid device loss, which increases the cost of treatment. In this study, PVA/anionic collagen membranes containing ciprofloxacin or tobramycin were prepared using two different methodologies, and the release, physical and antimicrobial properties were evaluated. The membrane containing ciprofloxacin was selected as a sustained drug delivery system with antibacterial activity against Staphylococcus aureus and Escherichia coli during 48 h. Despite to be opaque, due to its heterogeneous morphology, this membrane had the adequate mechanical strength, water content, hydrophilicity, water vapor permeability, and surface pH to interact with cornea without causing discomfort. In the surface of this membrane it was observed dispersed collagen fibrils which could serve as a substrate for corneal proteinases, contributing to the reduction in stromal damage and enhancing the epithelium regeneration. These results encourage the idea these membranes are new cost-effective and safe alternatives to treat corneal ulcers in animal patients.

Safety and efficacy of hydroxyapatite scaffold in the prevention of jaw osteonecrosis in vivo.

Two scaffolds of chitosan/sodium alginate/hydroxyapatite (Ch/NaAlg/Hap) 1:1:0.2 and 1:1:0.6 were evaluated in the prevention of bisphosphonate-induced jaw osteonecrosis. Two groups of rats (n = 24, according to the euthanasia time: 15 or 30 days after the last Zoledronic acid (ZA) administration) were subdivided in four subgroups (n = 6): I - Control (saline + teeth extraction); II - ZA 0.6 mg/kg + teeth extraction; III - ZA + teeth extraction + scaffold 1:1:0.2; IV - ZA + teeth extraction + scaffold 1:1:0.6. Jaws were evaluated histologically and blood was evaluated for hematological and biochemical parameters. Histopathology showed significant osteonecrosis in AZ group. The scaffold's implantation, despite the inflammatory process, were able to prevent the osteonecrosis. In the 15-day euthanasia group, an increase in red blood cells and platelets was observed in the subgroup II. Hemoglobin and hematocrit decreased in subgroup IV compared to II. Hepatic transaminases and creatinine concentration increased significantly in subgroup II. Calcium concentration increased in subgroup IV compared to II. In the 30-day euthanasia group, no differences among the groups were observed for any parameter. Scaffolds proved to be efficient and safe to liver and kidney function. Some hematological parameters were altered by the scaffold, but returned to normal concentrations over time. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1799-1808, 2018.

Bacterial Nanocellulose Loaded with Bromelain: Assessment of Antimicrobial, Antioxidant and Physical-Chemical Properties.

Bacterial nanocellulose (BNC) has desirable properties for wound healing such as high purity, good shape retention, and high water binding capacity. Bromelain is a protease found in pineapple tissues and has been applied in several fields, it has anti-inflammatory and anticancer properties, promotes cell apoptosis, amongst others. In this work, a BNC based device for the controlled release of bromelain was developed. BNC were submersed in sterilized bromelain solution and incubated at 25 °C under 100 rpm for 24 h. Physical-chemical properties, protein concentration, antioxidant and antimicrobial activities were measured. Results demonstrate that BNC could improve bromelain antimicrobial activity 9 times. Those findings allow concluding that bromelain is a promising molecule to be incorporated into BNC's. The BNC's characteristics seem to represent a new promising delivery system of the loaded biomolecule, and protected from external actions.

Development of praziquantel-loaded PLGA nanoparticles and evaluation of intestinal permeation by the everted gut sac model.

Praziquantel has been shown to be highly effective against all known species of Schistosoma infecting humans. Spherical nanoparticles made of poly(D,L-lactide-co-glycolide) acid with controlled size were designed as drug carriers. Praziquantel, a hydrophobic drug, was entrapped into the polymeric nanoparticles with 30% (w/w) of theoretical loading. The nanoparticles size was approximately of 350 nm with 66% of encapsulation efficiency. The everted gut sac model shows to be efficient to evaluate the drug permeation through the intestinal membrane. The results show that free praziquantel presents 4-fold times more permeation than praziquantel-loaded PLGA nanoparticles and physical mixture. For this drug, in special, this result can be interesting, since the nanoparticulate system can behave as a drug reservoir and/or to have a more localized effect in intestinal membrane for a prolonged period of time, since great amounts of parasites can be usually found in the mesenteric veins.

Liposomes and micro/nanoparticles as colloidal carriers for nasal drug delivery.

The use of the nasal route for drug delivery has attracted much interest in recent years in the pharmaceutical field. Local and principally systemic drug delivery can be achieved by this route of administration. But the nasal route of delivery is not applicable to all drugs. Polar drugs and some macromolecules are not absorbed in sufficient concentration due to poor membrane permeability, rapid clearance and enzymatic degradation into the nasal cavity. Thus, alternative means that help overcome these nasal barriers are currently in development. Absorption enhancers such as phospholipids and surfactants are constantly used, but care must be taken in relation to their concentration. Drug delivery systems including liposomes, cyclodextrins, micro- and nanoparticles are being investigated to increase the bioavailability of drugs delivered intranasally. This review article discusses recent progress and specific development issues relating to colloidal drug delivery systems in nasal drug delivery.

Colloidal carriers for ophthalmic drug delivery.

To achieve effective drug concentration at the intended site for a sufficient period of time is a requisite desired for many drug formulations. For drugs intended to ocular delivery, its poor bioavailability is due to pre-corneal factors. Most ocular diseases are treated by topical drug application in the form of solution, suspension and ointment. However, such dosage forms are no longer sufficient to combat some ocular diseases. Intravitreal drug injection is the current therapy for disorders in posterior segment. The procedure is associated with a high risk of complications, particularly when frequent, repeated injections are required. Thus, sustained-release technologies are being proposed, and the benefits of using colloidal carriers in intravitreal injections are currently under investigation for posterior drug delivery. This review will discuss recent progress and specific development issues relating to colloidal drug delivery systems, such as liposomes, niosomes, nanoparticles, and microemulsions in ocular drug delivery.

Development and in vitro evaluation of coated pellets containing chitosan to potential colonic drug delivery.

In this work pellets containing chitosan for colonic drug delivery were developed. The influence of the polysaccharide in the pellets was evaluated by swelling, drug dissolution and intestinal permeation studies. Drug-loaded pellets containing chitosan as swellable polymer were coated with an inner layer of Kollicoat(®) SR 30 D and an outer layer of the enteric polymer Kollicoat(®) MAE 30 DP in a fluidized-bed apparatus. Metronidazole released from pellets was assessed using Bio-Dis dissolution method. Swelling, drug release and intestinal permeation were dependent on the chitosan and the coating composition. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. The film coating was found to be the main factor controlling the drug release and the chitosan controlling the drug intestinal permeation. Coated pellets containing chitosan show great potential as a system for drug delivery to the colon.

A novel dosage form for buccal administration of bupropion

Bupropion is an antidepressant used in the treatment of smoking. The purpose of this study was to prepare controlled-release hydrogel films for buccal administration of bupropion and investigate its physicochemical and cytotoxic properties. The films were prepared from ultrapure sodium carboxymethylcellulose, hydroxypropylmethylcellulose K4M, and medium-viscosity chitosan. Evaluation of film physicochemical characteristics was based on scanning electron microscopy, bupropion content, mechanical strength (burst strength, relaxation, resilience, and traction), and cytotoxicity. Bupropion content in bilayer films was 121 mg per 9 cm2. The presence of bupropion modified film mechanical strength, but did not compromise the use of this pharmaceutical form. As shown by the cytotoxicity results, films containing bupropion did not cause cellular damage. Bupropion administration in the form of hydrogel films is a potentially useful alternative in the treatment of smoking.

A bupropiona é um antidepressivo utilizado no tratamento do tabagismo. O objetivo deste trabalho foi a preparação de filmes hidrogelatinosos de liberação controlada para administração bucal de bupropiona. Os filmes foram preparados utilizando carboximetilcelulose sódica ultrapurificada, hidroxipropilmetilcelulose K4M e quitosana de média viscosidade. As características físico-químicas dos filmes foram avaliadas por microscopia eletrônica de varredura, teor de bupropiona, resistência mecânica (perfuração, relaxação, resiliência e tração) e citotoxicidade. Os resultados mostraram que os filmes em bicamada apresentaram teor de bupropiona de 121 mg por 9 cm2 de filme e que a bupropiona modifica a resistência mecânica dos filmes, sem, no entanto, inviabilizar o uso desta forma farmacêutica. Os estudos de citotoxicidade mostraram que as formulações dos filmes contendo bupropiona não causam dano celular. Este estudo mostrou que a bupropiona veiculada na forma de filme hidrogelatinoso pode ser uma alternativa útil no tratamento do tabagismo.