A new way of valorizing biomaterials: the use of sunflower protein for 1 a-tocopherol microencapsulation

Biopolymer based microparticles were efficiently prepared from sunflower protein (SP) wall material and a-tocopherol (T) active core using a spray-drying technique. Protein enzymatic hydrolysis and/or N-acylation were carried out to make some structural modifications to the vegetable protein. Native and hydrolyzed SP were characterized by Asymmetrical Flow Field-Flow Fractionation (AsFlFFF). Results of AsFlFFF confirmed that size of proteinic macromolecules was influenced by degree of hydrolysis. The effect of protein modifications and the influence of wall/core ratio on both emulsions and microparticle properties were evaluated. Concerning emulsion properties, enzymatic hydrolysis involved a decrease in viscosity, whereas acylation did not significantly affect emulsion droplet size and viscosity. Microparticles obtained with hydrolyzed SP wall material showed lower retention efficiency (RE) than native SP microparticles (62-80% and 93% respectively). Conversely, acylation of both hydrolyzed SP and native SP allowed a higher RE to be reached (up to 100%). Increasing T concentration increased emulsion viscosity, emulsion droplet size, microparticle size, and enhanced RE. These results demonstrated the feasibility of high loaded (up to 79.2% T) microparticles

Development and evaluation of ofloxacin orally disintegrating tablets

Bitter taste of ofloxacin, a broad spectrum bactericidal agent, is masked and orally disintegrating tablets were formulated. The bitter taste is masked by forming complex between drug and weak cation exchange resins, Tulsion 335 and Indion 204. Effect of pH and drug:resin ratio on the drug loading was studied. Maximum drug loading was observed at pH 6. Ratio of 1:2 of drug:resin masked almost complete bitterness of ofloxacin. Formation of complexes was confirmed by IR spectroscopy. Physical characterization of taste masked complexes was carried out. Present work envisages the taste masking of ofloxacin and development of orally disintegrating tablets. The effect of pH and resin quantities on drug loading were studied to find the optimum conditions of drug loading for complete taste masking. Effect of superdisintegrants like sodium starch glycolate, croscarmellose sodium and polyplasdone XL at varying level on physical parameters of compressed tablets was also assessed. The formulations containing 5 % w/w polyplasdone XL showed about 90 % of drug release within 5 minutes. No significant differences were observed in the physical parameters of resinates as well as tablets prepared from Tulsion 335 and Indion 204.O gosto amargo de ofloxacina, agente bactericida de largo espectro, é mascarado e formularam-se comprimidos dispersíveis. O sabor amargo é mascarado pela formação de complexo entre o fármaco e resinas de troca catiônica fraca, Tulsion 335 e Indion 204. Efeito do pH e da proporção fármaco: resina sobre a carga de fármaco foi estudada. Carga de fármaco máxima foi observada em pH 6. Proporção 1:2 do fármaco: resina mascarou quase completamente o gosto amargo de ofloxacina. A formação de complexos foi confirmada por espectroscopia no IV. Caracterização física dos complexos de sabor mascarado foi realizada. O presente trabalho preconiza o mascaramento do gosto de ofloxacina e desenvolvimento decomprimidos por via oral, se desintegrando. O efeito do pH e da resina quantidades de carga de fármaco foram estudadas paraencontrar as condições óptimas de carga de fármaco para dissimulação do saborcompleto. Efeito da superdisintegrants como amido glicolato de sódio, croscarmelose sódica e Polyplasdone XL em diferentes níveis de parâmetros físicos de comprimidos também avaliados foi avaliada. As formulações contendo 5 %w/w Polyplasdone XL mostraram cerca de 90% de libertação do fármaco no prazo de 5 minutos. Não foram observadas diferenças significativas nos parâmetros físicos de resinatosbem como comprimidos preparados a partir de Tulsion 335 e Indion 204

Letrozole-loaded nonionic surfactant vesicles prepared via a slurry-based proniosome technology: Formulation development and characterization

Slurry-based Letrozole (LTZ)-loaded proniosomes were designed using sucrose or sorbitol as carriers and various ratios of cholesterol (CH) and Tween 80 (T80) as lipid composition. Proniosomes were hydrated and probe-sonicated to generate nano-vesicles. The proniosome powders were characterized in terms of morphology using scanning electron microscopy, and drug crystallinity using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The niosomes generated from proniosomes were characterized and compared to conventional niosomes, in terms of size, zeta potential, drug entrapment, storage stability, and drug release. All formulations had size measurements in the range of 100–194 nm, polydispersity index (PDI) values below 0.3, and zeta potential values below – 23 mV. Drug entrapment was the highest for niosomes generated from sucrose-based proniosomes (CH:T80; 1:1), reaching 74% compared to less than 50% for conventional niosomes. Storage for 3 months at 4 °C resulted in minor drug leakage whilst most drug was leaked from vesicles stored at room temperature. DSC and XRD studies showed that LTZ was converted into its amorphous form upon incorporation into proniosomes. Drug release exhibited a biphasic pattern, being fast at the first 24 h (up to 65% released) followed by a very slow release phase for a duration of one month, releasing at least 95%. The release profile of niosomes fits best with the Higuchi model. Overall, in this study, a facile approach to generating niosomes incorporating LTZ using a slurry-based proniosome technology was demonstrated. The niosomes provided high drug entrapment and controlled biphasic release over one month

Nanosizing techniques for improving bioavailability of drugs

The poor solubility of significant number of Active Pharmaceutical Ingredients (APIs) has become a major challenge in the drug development process. Drugs with poor solubility are difficult to formulate by conventional methods and often show poor bioavailability. In the last decade, attention has been focused on developing nanocrystals for poorly water soluble drugs using nanosizing techniques. Nanosizing is a pharmaceutical process that changes the size of a drug to the sub-micron range in an attempt to increase its surface area and consequently its dissolution rate and bioavailability. The effectiveness of nanocrystal drugs is evidenced by the fact that six FDA approved nanocrystal drugs are already on the market. The bioavailabilities of these preparations have been significantly improved compared to their conventional dosage forms. There are two main approaches for preparation of drug nanocrystals; these are the top-down and bottom-up techniques. Top-down techniques have been successfully used in both lab scale and commercial scale manufacture. Bottom-up approaches have not yet been used at a commercial level, however, these techniques have been found to produce narrow sized distribution nanocrystals using simple methods. Bottom-up techniques have been also used in combination with top-down processes to produce drug nanoparticles. The main aim of this review article is to discuss the various methods for nanosizing drugs to improve their bioavailabilities

Synthesis and properties of a biodegradable polymer-drug conjugate: Methotrexate-poly(glycerol adipate)

Polymer-drug conjugates have been actively developed as potential anticancer drug delivery systems. In this study, we report the first polymer-anticancer drug conjugate with poly(glycerol adipate) (PGA) through the successful conjugation of methotrexate (MTX). MTX-PGA conjugates were controllably and simply fabricated by carbodiimide-mediated coupling reaction with various high molar ratios of MTX. The MTX-PGA conjugate self-assembled into nanoparticles with size dependent on the amount of conjugated MTX and the pH of medium. Change in particle size was attributed to steric hindrance and bulkiness inside the nanoparticle core and dissociation of free functional groups of the drug. The MTX-PGA nanoparticles were physically stable in media with pH range of 5–9 and ionic strength of up to 0.15 M NaCl and further chemically stable against hydrolysis in pH 7.4 medium over 30 days but enzymatically degradable to release unchanged free drug. Although 30%MTX-PGA nanoparticles exhibited only slightly less potency than free MTX in 791T cells in contrast to previously reported human serum albumin-MTX conjugates which had >300 times lower potency than free MTX. However, the MTX nanoparticles showed 7 times higher toxicity to Saos-2 cells than MTX. Together with the enzymic degradation experiments, these results suggest that with a suitable biodegradable polymer a linker moiety is not a necessary component. These easily synthesised PGA drug conjugates lacking a linker moiety could therefore be an effective new pathway for development of polymer drug conjugates

Innovative Design of Targeted Nanoparticles: Polymer–Drug Conjugates for Enhanced Cancer Therapy

Polymer–drug conjugates (PDCs) have shown great promise in enhancing the efficacy and safety of cancer therapy. These conjugates combine the advantageous properties of both polymers and drugs, leading to improved pharmacokinetics, controlled drug release, and targeted delivery to tumor tissues. This review provides a comprehensive overview of recent developments in PDCs for cancer therapy. First, various types of polymers used in these conjugates are discussed, including synthetic polymers, such as poly(↋-caprolactone) (PCL), D-α-tocopheryl polyethylene glycol (TPGS), and polyethylene glycol (PEG), as well as natural polymers such as hyaluronic acid (HA). The choice of polymer is crucial to achieving desired properties, such as stability, biocompatibility, and controlled drug release. Subsequently, the strategies for conjugating drugs to polymers are explored, including covalent bonding, which enables a stable linkage between the polymer and the drug, ensuring controlled release and minimizing premature drug release. The use of polymers can extend the circulation time of the drug, facilitating enhanced accumulation within tumor tissues through the enhanced permeability and retention (EPR) effect. This, in turn, results in improved drug efficacy and reduced systemic toxicity. Moreover, the importance of tumor-targeting ligands in PDCs is highlighted. Various ligands, such as antibodies, peptides, aptamers, folic acid, herceptin, and HA, can be incorporated into conjugates to selectively deliver the drug to tumor cells, reducing off-target effects and improving therapeutic outcomes. In conclusion, PDCs have emerged as a versatile and effective approach to cancer therapy. Their ability to combine the advantages of polymers and drugs offers enhanced drug delivery, controlled release, and targeted treatment, thereby improving the overall efficacy and safety of cancer therapies. Further research and development in this field has great potential to advance personalized cancer treatment options

Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

AbstractNanocrystals, a carrier-free colloidal delivery system in nano-sized range, is an interesting approach for poorly soluble drugs. Nanocrystals provide special features including enhancement of saturation solubility, dissolution velocity and adhesiveness to surface/cell membranes. Several strategies are applied for nanocrystals production including precipitation, milling, high pressure homogenization and combination methods such as NanoEdge™, SmartCrystal and Precipitation-lyophilization-homogenization (PLH) technology. For oral administration, many publications reported useful advantages of nanocrystals to improve in vivo performances i.e. pharmacokinetics, pharmacodynamics, safety and targeted delivery which were discussed in this review. Additionally, transformation of nanocrystals to final formulations and future trends of nanocrystals were also described