Development of enteric-coated, biphasic chitosan/HPMC microcapsules for colon-targeted delivery of anticancer drug-loaded nanoparticles.

Oral delivery of anticancer drug-loaded nanoparticles (NPs) to the colon offers opportunities to improve colorectal cancer (CRC) treatment by increasing the free drug concentration at tumour sites and/or enhancing NP accumulation in tumours. Indomethacin, 5-FU and curcumin, were entrapped separately in Eudragit RS NPs (approximately 10% w/w loading) using nanoprecipitation and incorporated in biphasic chitosan/HPMC microcapsules (MCs) using aerosolisation. The MCs were designed to release NPs primarily in the colon following chitosan breakdown by bacterial enzymes.

In Vitro Evaluation of Eudragit Matrices for Oral Delivery of BCG Vaccine to Animals.

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally, but oral delivery is highly advantageous for the immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in phosphate-buffered saline (PBS), containing Tween 80, with and without the addition of mannitol or trehalose.

Formulation strategies for achieving high delivery efficiency of thymoquinone-containing extract to the colon based on oral alginate microcapsules for treatment of inflammatory bowel disease.

extract (NSE) was incorporated in alginate microcapsules using aerosolisation and homogenisation methods, respectively, with the aim of delivering high concentrations of the active species, thymoquinone (TQ), directly to sites of inflammation in the colon following oral administration. Encapsulation of NSE was accomplished either by direct loading or diffusion into blank microparticles. Microcapsules in the size range 40-60 µm exhibited significantly higher NSE loading up to 42% w/w and encapsulation efficiency (EE) up to 63% when the extract was entrapped by direct encapsulation compared with 4.

Controlled delivery of the antiprotozoal agent (tinidazole) from intravaginal polymer matrices for treatment of the sexually transmitted infection, trichomoniasis.

Microporous polymeric matrices prepared from poly(ɛ-caprolactone) [PCL] were evaluated for controlled vaginal delivery of the antiprotozoal agent (tinidazole) in the treatment of the sexually transmitted infection, trichomoniasis. The matrices were produced by rapidly cooling co-solutions of PCL and tinidazole in acetone to -80 °C to induce crystallisation and hardening of the polymer. Tinidazole incorporation in the matrices increased from 1.

Sustained Simultaneous Delivery of Metronidazole and Doxycycline From Polycaprolactone Matrices Designed for Intravaginal Treatment of Pelvic Inflammatory Disease.

Poly(ɛ-caprolactone) (PCL) intravaginal matrices were produced for local delivery of a combination of antibacterials, by rapidly cooling a mixture of drug powders dispersed in PCL solution. Matrices loaded with different combinations of metronidazole (10%, 15%, and 20% w/w) and doxycycline (10% w/w) were evaluated in vitro for release behavior and antibacterial activity. Rapid "burst release" of 8%-15% of the doxycycline content and 31%-37% of the metronidazole content occurred within 24 h when matrices were immersed in simulated vaginal fluid at 37°C.

Production and in vitro evaluation of macroporous, cell-encapsulating alginate fibres for nerve repair.

The prospects for successful peripheral nerve repair using fibre guides are considered to be enhanced by the use of a scaffold material, which promotes attachment and proliferation of glial cells and axonal regeneration. Macroporous alginate fibres were produced by extraction of gelatin particle porogens from wet spun fibres produced using a suspension of gelatin particles in 1.5% w/v alginate solution.

A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon.

Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation.

In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing.

Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity.

Investigation of Polycaprolactone Matrices for Intravaginal Delivery of Doxycycline.

Polycaprolactone (PCL) matrices loaded with doxycycline were produced by rapidly cooling suspensions of the drug powder in PCL solution in acetone. Drug loadings of 5%, 10%, and 15% (w/w) of the PCL content were achieved. Exposure of doxycycline powder to matrix processing conditions in the absence of PCL revealed an endothermic peak at 65°C with the main peak at 167°C, suggesting solvatomorph formation.

The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery.

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h.

Synergistic activity of tenofovir and nevirapine combinations released from polycaprolactone matrices for potential enhanced prevention of HIV infection through the vaginal route.

Polycaprolactone (PCL) matrices were simultaneously loaded with the antiviral agents, tenofovir (TFV) and nevirapine (NVP), in combination to provide synergistic activity in the prevention of HIV transmission through the vaginal route. TFV and NVP were incorporated in PCL matrices at theoretical loadings of 10%TFV-10% NVP, 5%TFV-5%NVP and 5%TFV-10%NVP, measured with respect to the PCL content of the matrices. Actual TFV loadings ranged from 2.

Evaluation of polycaprolactone matrices for sustained vaginal delivery of nevirapine in the prevention of heterosexual HIV transmission.

Nevirapine (NVP) was loaded in polycaprolactone (PCL) matrices to produce vaginal inserts with the aim of preventing HIV transmission. NVP dispersions in PCL were prepared, at 10% (w/w) theoretical loading, measured with respect to the PCL content of the matrices, in the form of (1) NVP only, (2) a physical mixture of NVP with polyethylene glycol (PEG) 6000 or (c) a solid dispersion (SD) with PEG produced by co-dissolution in ethanol. Characterisation of SD by differential scanning calorimetry and attenuated total reflectance-Fourier transform infrared spectroscopy suggested transformation of the crystalline structure of NVP to an amorphous form which consequently increased the dissolution rate of drug.

Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis.

Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.

Designing colon-specific delivery systems for anticancer drug-loaded nanoparticles: an evaluation of alginate carriers.

Incorporation of drug-loaded nanoparticles (NPs) in colon-specific delivery systems shows potential for raising local drug concentrations, tumor targeting and improving chemotherapy. Alginate microcapsules (15-80 µm diameter) containing insoluble Eudragit(®) RS NPs as models were characterized precisely in terms of NP loading and release kinetics. High NP loading (22%, w/w of the dried microcapsules) combined with negligible release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggested that high concentrations of NPs could be transported to the colon.

An evaluation of polycaprolactone matrices for vaginal delivery of the antiviral, tenofovir, in preventing heterosexual transmission of HIV.

Tenofovir was incorporated in controlled-release polycaprolactone (PCL) matrices designed for production of vaginal inserts for prevention of HIV transmission. Rapid cooling of suspensions of the drug powder in PCL solution resulted in micro-porous matrices with tenofovir loadings up to 12% (w/w) and high incorporation efficiencies in excess of 90%. The release behaviour of tenofovir in simulated vaginal fluid (SVF) demonstrated high delivery efficiency of 85%-99% over 30 days and could be described effectively by a first-order kinetics model giving a mean value of 0.

Evaluation of microporous polycaprolactone matrices for controlled delivery of antiviral microbicides to the female genital tract.

Acyclovir (ACV) as a model antiviral microbicide, was incorporated in controlled-release polycaprolactone (PCL) matrices designed for application as intra-vaginal ring inserts (IVRs). Microporous materials incorporating acyclovir up to a level of ~10 % w/w were produced by rapidly cooling suspensions of drug powder in PCL solution followed by solvent extraction from the hardened matrices. Around 21, 50 and 78 % of the drug content was gradually released from matrices over 30 days in simulated vaginal fluid at 37 °C, corresponding to drug loadings of 5.

Development of intra-vaginal matrices from polycaprolactone for sustained release of antimicrobial agents.

Microporous poly(ε-caprolactone) matrices were loaded with an antibacterial agent, ciprofloxacin and an antifungal agent, miconazole nitrate, respectively, for investigations of their potential as controlled vaginal delivery devices. Ciprofloxacin loadings up to 15% w/w could be obtained by increasing the drug content of the poly(ε-caprolactone) solution, while the actual loadings of miconazole were much lower (1-3% w/w) due to drug partition into methanol during the solvent extraction. The kinetics of ciprofloxacin release in simulated vaginal fluid at 37 were characterised by a small burst release phase in the first 24 h, low drug release up to 7 days (10%) and gradual release of up to 80% of the drug content by day 30.

Evaluation of Lactobacillus rhamnosus GG and Lactobacillus acidophilus NCFM encapsulated using a novel impinging aerosol method in fruit food products.

This study investigated the effect of microencapsulation on the survival of Lactobacillus rhamnosus GG and Lactobacillus acidophilus NCFM and their acidification in orange juice at 25°C for nine days and at 4°C over thirty five days of storage. Alginate micro beads (10-40 μm) containing the probiotics were produced by a novel dual aerosol method of alginate and CaCl(2) cross linking solution. Unencapsulated L.

Novel alginate gel microspheres produced by impinging aerosols for oral delivery of proteins.

Lysozyme and insulin were encapsulated in alginate gel microspheres using impinging aerosols method. High loadings of around 50% weight/dry microspheres weight were obtained with encapsulation efficiencies of at least 48%. Environmental scanning electron microscopy revealed smooth spherical hydrated microspheres (30-60 µm) in diameter.

A novel impinging aerosols method for production of propranolol hydrochloride-loaded alginate gel microspheres for oral delivery.

Propranolol hydrochloride was directly encapsulated in alginate gel microspheres (40-50 µm in diameter) using a novel method involving impinging aerosols of CaCl(2) cross-linking solution and sodium alginate solution containing the drug. Microspheres formulated using 0.1 M CaCl(2) exhibited the highest drug loading (14%, w/w of dry microspheres) with 66.

Diffusion loading and drug delivery characteristics of alginate gel microparticles produced by a novel impinging aerosols method.

Microencapsulation of a hydrophilic active (gentamicin sulphate (GS)) and a hydrophobic non-steroidal anti-inflammatory drug (ibuprofen) in alginate gel microparticles was accomplished by molecular diffusion of the drug species into microparticles produced by impinging aerosols of alginate solution and CaCl(2) cross-linking solution. A mean particle size in the range of 30-50 µm was measured using laser light scattering and high drug loadings of around 35 and 29% weight/dry microparticle weight were obtained for GS and ibuprofen respectively. GS release was similar in simulated intestinal fluid (phosphate buffer saline (PBS), pH 7.

Micro-CT analysis of matrix-type drug delivery devices and correlation with protein release behaviour.

A series of matrix-type drug delivery devices comprising a continuous phase of microporous poly(epsilon-caprolactone) (PCL) and a dispersed phase of protein particles (gelatin) with defined size ranges (45-90, 90-125 and 125-250 microm) were produced by rapidly cooling suspensions in dry ice followed by solvent extraction from the hardened material. High protein loadings (38-44%, w/w) were achieved and highly efficient protein release (90% of the initial load) was obtained over time periods of 3-11 days depending on particle loading and size range. The duration of protein release was extended from 3 to 11 days by reducing the protein load.

On the determination of Darcy permeability coefficients for a microporous tissue scaffold.

Structural characterization of porous tissue scaffolds is challenging due to their complexity. Most investigators report the porosity of the material together with an estimate of the mean pore size and the pore size distribution. The usefulness of these measures is limited, especially in predicting the time-dependent permeation characteristics of a biodegradable, cell-seeded scaffold.

Delivery of bioactive macromolecules from microporous polymer matrices: Release and activity profiles of lysozyme, collagenase and catalase.

Microporous polycaprolactone (PCL) matrices containing lysozyme, collagenase and catalase respectively with molecular weight covering a wide range from 14.3 to 240kDa were produced by a novel method involving rapid cooling of particle suspensions in dry ice. The enzyme loading efficiency (lysozyme (50%), collagenase (75%) and catalase (90%)) depended on the enzyme molecular weight and the non-solvent used to extract acetone from the hardened matrices.