PEGylated polymeric nanocapsules for oral delivery of trypsin targeted to the small intestines.

The lack of trypsin in the intestines may end up with malnutrition; thus, trypsin replacement therapy is required in such cases. The main objective of this study is to formulate and evaluate polymeric nanocapsule (PNC) systems able to deliver trypsin to the small intestines with the minimal release in the stomach with the maximum biological activity. Four nanocapsule formulations were prepared by double emulsion/evaporation method as w/o/w and s/o/w. Particle size, encapsulation efficiencies, drug release in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF), morphology, the biological activity of encapsulated trypsin and shelf-life stability were investigated for all formulations. All formulations had a spherical shape with submicron size, and encapsulation efficiency more than 80%. The biological activity of encapsulated trypsin was significantly affected by the amount of trehalose and whether the formulations were prepared as s/o/w or w/o/w (P < 0.05). Most of the encapsulated protein was released sustainedly at the target site (SIF) over 24 h with minimum amount release in the gastric fluids. Also, more than 90% of physical integrity trypsin encapsulated in all formulations was retained after storage under chilled conditions for six months. However, the enzymatic assay results show that with low trehalose content, the biological activity was low, while increasing the trehalose amount increased the shelf stability to reach around 100% after six months of the study. The results obtained in this research work clearly indicated a promising potential of controlled release polymeric nanocapsules containing trypsin to target the small intestine and protect trypsin from the harsh condition facing the proteins during the process of preparation or the period of storage.

Dissolution of ibuprofen from spray dried and spray chilled particles.

The formulation of hydrophobic drugs for oral drug delivery is challenging due to poor solubility, poor dissolution and poor wetting of these drugs. Consequently, the aim of this study was to improve the dissolution of a model poorly water soluble drug, ibuprofen. Microparticles containing ibuprofen were produced by spray drying and spray chilling technology in the absence/presence of a hydrophilic surfactant. Poloxamer 127, tri-block copolymer, was chosen as the hydrophilic surfactant to improve drug particle wettability and hence the dissolution rate. The prepared formulations were evaluated for in vitro dissolution and intrinsic solubility. In addition, the produced drug particles were characterised by scanning electron microscopy (SEM), differential scanning calorimeter (DSC) and Fourier transform infrared spectroscopy (FT-IR). SEM revealed changes in the surface morphology of processed ibuprofen, suggesting the effective formation of the drug particles. DSC data showed shifting of the melting peak of the drug towards lower melting temperature in the prepared particles, indicating the possibility of drug /polymer interaction. The results of the dissolution studies of spray dried ibuprofen and spray dried ibuprofen/Poloxamer 127 particles showed significantly (P<0.05) increased percentage drug release compared to control (ibuprofen raw material). For spray chilling, the prepared particles did not improve the dissolution of the drug, the dissolution was even less than that of the control. DSC and FT-IR results demonstrated that spray drying reduced drug crystallinity, but for spray chilled particles there was evidence of polymorphic changes in the drug with and without the surfactant. Consequently, it is believed that spray drying of ibuprofen is a useful tool to improve wettability, solubility and hence the dissolution behaviour of poorly water soluble drugs, in contrast to spray chilling technique.

Lysozyme and DNase I loaded poly (D, L lactide-co-caprolactone) nanocapsules as an oral delivery system.

Clinical applications of oral protein therapy for the treatment of various chronic diseases are limited due to the harsh conditions encounter the proteins during their journey in the Gastrointestinal Tract. Although nanotechnology forms a platform for the development of oral protein formulations, obtaining physiochemically stable formulations able to deliver active proteins is still challenging because of harsh preparation conditions. This study proposes the use of poly (D, L-lactic-co-caprolactone)-based polymeric nanocapsules at different monomers' ratios for protein loading and oral delivery. All formulations had a spherical shape and nano-scale size, and lysozyme encapsulation efficiency reached 80% and significantly affected by monomers' ratio. Trehalose and physical state of lysozyme had a significant effect on its biological activity (P < 0.05). Less than 10% of the protein was released in simulated gastric fluid, and 73% was the highest recorded accumulative release percentage in simulated intestinal fluid (SIF) over 24 h. The higher caprolactone content, the higher encapsulation efficiency (EE) and the lower SIF release recorded. Therefore, the formulation factors were optimised and the obtained system was PEGylated wisely to attain EE 80%, 81% SIF release within 24 h, and 98% lysozyme biological activity. The optimum formulation was prepared to deliver DNase, and similar attributes were obtained.

Physical Characterisation as an Insight into a Gene Delivery System Containing Cyclodextrins with Pluronic®-F127 and Folic acid as Non-Viral Vectors.

Gene delivery into cells offers opportunities to treat various human genetic diseases. Effective gene delivery is dependent on its stability and ability to transfect across cells. DNA is susceptible to enzymatic degradation and its negatively charge are barriers towards successful transfection. DNA has to be protected from degradation and neutralised. Non-viral vectors are preferred carrier systems, therefore, the use of cyclodextrins with Pluronic(®)-F127 and folic acid at different concentrations to stabilise the formulation was investigated. Formulations were characterised in fresh and freeze dried forms. DNA stability in formulations was tested by determining the stability of DNA against enzymatic degradation. Degree of DNA inclusion into cyclodextrins was investigated using fluorescence spectroscopy. Thermal behaviour was studied using Differential Scanning Calorimetry (DSC). Incorporation of Pluronic(®)-F127 produced most stable formulations regarding enzymatic degradation. These formulations show high percentage inclusion. Shift of peaks in FTIR data, appearance of uniform particulate as detected by SEM and changing in the denaturation temperature as demonstrated by DSC data for Pluronic(®)-F127 containing formulations confirm clear interaction between Pluronic(®)-F127 and cyclodextrin/ DNA complex. It was noted that γ-cyclodextrin provide better protection and inclusion compared to ß-cyclodextrin. Pluronic(®)-F127 with cyclodextrins is a promising combination to improve stability.

Effects of liquisolid formulations on dissolution of naproxen.

The aim of this study was to investigate the use of liquisolid technique in improving the dissolution profiles of naproxen in a solid dosage form. This study was designed to evaluate the effects of different formulation variables, i.e. type of non-volatile liquid vehicles and drug concentrations, on drug dissolution rates. The liquisolid tablets were formulated with three different liquid vehicles, namely Cremophor EL (polyoxyl 35 castor oil), Synperonic PE/L61 (poloxamer 181, polyoxyethylene-polyoxypropylene copolymer) and poly ethylene glycol 400 (PEG400) at two drug concentrations, 20%w/w and 40%w/w. Avicel PH102 was used as a carrier material, Cab-o-sil M-5 as a coating material and maize starch as a disintegrant. The empirical method as introduced by Spireas and Bolton (1999) [1] was applied strictly to calculate the amounts of coating and carrier materials required to prepare naproxen liquisolid tablets. Quality control tests, i.e. uniformity of tablet weight, uniformity of drug content, tablet hardness, friability test, disintegration and dissolution tests were performed to evaluate each batch of prepared tablets. In vitro drug dissolution profiles of the liquisolid formulations were studied and compared with conventional formulation, in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2) without enzyme. Stability studies were carried out to evaluate the stability of the tablets under humid conditions. Differential scanning calorimetry and Fourier transform infrared were used to investigate physicochemical interaction between naproxen and the excipients. It was found that liquisolid tablets formulated with Cremophor EL at drug concentration of 20%w/w produced high dissolution profile with acceptable tablet properties. The stability studies showed that the dissolution profiles of liquisolid tablets prepared with Cremophor EL were not affected by ageing significantly. Furthermore, DSC revealed that drug particles in liquisolid formulations were completely solubilised.