Preparation of snail cyst and PEG-4000 composite carriers via PEGylation for oral delivery of insulin: An in vitro and in vivo evaluation

Purpose: To develop PEGylated mucin as a carrier system for oral insulin delivery. Methods: Varied ratios of snail cyst were molecularly modified with polyethylene glycol 4000 (PEG 4000). Briefly, In each case, 20 g quantities of snail cyst and PEG 4000 were separately dispersed in distilled water, stirred and allowed to stand for 24 h to produce a homogeneous dispersion and clear solution, respectively. The solution of PEG was added to the snail cyst dispersion, stirred and allowed 12 h for molecular interaction. The mixture was added to a 250-mL beaker containing 100 mL of light liquid paraffin. The microparticles were obtained after stirring and removing the paraffin using chilled acetone. The obtained PEGylated mucin matrices, which were subsequently loaded with insulin using a diffusion method, characterized for particles size, drug loading, encapsulation efficiency, in vitro drug release and evaluated for oral application in diabetic rats. Results: The polymer hybrids improved insulin encapsulation efficiency (max 82.3 %), gave. polydispersity indices that ranged from 0.11 ± 0.1 to 0.24 ± 0.2, zeta potential values between 28 ± 0.3 and 38 ± 1.1 mV. Insulin release was highest (68 % in 6 h) for batch C and was sustained for 10 h in simulated intestinal fluid. The optimized batch (C-5) showed higher hypoglycaemic activity (56.5 %) than control (0.5 %) in diabetic rats. Conclusion: The results suggest that PEGylated mucin can potentially be developed as a platform for oral insulin deliver

Biochemical, rheological and hydrophile-lipophile balance (HLB) evaluation of Archachatina marginata (snail) mucin extract for possible nutraceutical and nano biopharmaceutical applications

Purpose: To evaluate the rheological, biochemical, hydrophile-lipophile balance (HLB) of Archachatina marginata (snail) mucin extract for possible use as a nutraceutical and nano biopharmaceutical material. Methods: Snail mucin was extracted with acetone and water, lyophilized and the biochemical, proximate and mineral analyses of the extracts were studied using standard methods. The rheological properties of the extracts (1, 2, 4 and 8 % w/v) and their emulsion-based preparations were evaluated. Other physicochemical properties and HLB values of the preparations were also determined. Results: Snail mucin extracts contained protein (84 %), fats (2.91 %) and carbohydrate (1.2 %) and showed significant nutraceutical composition (p < 0.05). Ash content of 4.21 and 4.12 % was obtained for water and acetone extracts, respectively. Moisture content was < 9 % for both the aqueous and nonaqueous mucin extracts. Potassium, calcium and phosphorus were present in high quantities in the extracts while iron, copper and zinc were in trace amounts (< 4 %). Mucin dispersions exhibited viscosity in the range of 0.89 to 0.93 cp. Water sorption and dry weight were higher in the acetone extract than in the aqueous extract. The HLB values, which ranged from 7 to 15, were within the acceptable values for material for nanobiopharmaceutical application, except that the acetone extract. Conclusion: Snail mucin exhibits good nutraceutical properties and also possesses good properties that render it a potential excipient for use in the formulation of drug delivery system

Formulation and characterization of artemether-loaded sodium alginate microcapsules

Purpose: To increase the solubility of artemether (ART) in Transcutol® HP through microencapsulation in sodium alginate polymer to achieve  sustained in vivo release.Method: Graded concentrations of ART (0.00, 0.25, 0.50, 0.75, and 1.00 g) microcapsules were produced using Tween® 80 by the cold  homogenization method at 24 x 1000 rpm for 15 min. Characterization based on yield, encapsulation efficiency (EE), particle size, pH stability,  differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and in vivo release using Peter’s four-day suppressive protocol in Wistar mice infected with Plasmodium berghei, were determined.Results: The results obtained indicate that 0.5 g ART-loaded microcapsules (AMC) showed the highest yield of 96.85 %. The EE of 88.3 %  corresponded to 0.75 g ART-loaded microcapsules. DSC results revealed that there was a significant reduction in enthalpy in all the formulations compared to the crystalline drug, but no strong bond interaction occurred except for the blank microcapsules. The AMC1.0 showed high dose-dependent plasmodial growth inhibition of 88.75 % while AMC0.25 had the least (68.13 %).Conclusion: The artemether microcapsules showed sustained release characteristics for oral delivery of artemether and therefore may reduce some of the adverse effects associated with high dose artemether therapy in conventional oral tablets. Keywords: Malaria, Artemether, Transcutol® HP, Sustained-release, RBC count, Antiplasmodial activit

Pharmacokinetics and biodistribution of zidovudine loaded in a solidified reverse micellar delivery system.

The aim of the research was to study the stability, release profile, pharmacokinetic and biodistribution properties of zidovudine (AZT)-solidified reverse micellar microparticulate. Lipid matrices formulated with Phospholipon® 90H and goat fat at ratios of 1:1, 2:1, 3:1 and 2:3 were used to prepare AZT-loaded SLM by melt dispersion followed by lyophilization. In vitro release studies of the drug were carried out using a sequential drug release method in both SGF (pH 1.2) and SIF (pH 7.2) while the in vivo drug release studies were carried out using Wistar albino rats. The result of our findings showed that the drug is compatibility with the lipid matrix with the 1:1 showing the most stable microparticle preparation which was then optimized. The formulations showed a concentration dependent increase in their concentration maximum (Cmax) with values of 116.05 µg/ml, 124.21 µg/ml, 128.95 µg/ml, 138.95 µg/ml and time to reach maximum concentration (Tmax) values of 5h, 8 h, 8 h, and 5 h for batches B1, B2, B3 and B4 containing 1 %, 2 %, 3 % and 5 % of AZT respectively. The area under curves (AUCs) of the microparticles formulated showed that the bioavailabilities of the microparticles were comparable to that of the conventional release tablet. The biodistribution studies of the microparticles in rats showed highest concentration of the drug in the liver with the least in the brain and higher biodistribution in various organs than pure AZT. The data suggested that SLM could be a promising drug delivery system to improve on the shortcomings of pharmacokinetics and bio-distribution properties of conventional AZT tablets like fluctuation in blood levels of the drug

Development and optimization of solid lipid nanoparticles coated with chitosan and poly(2-ethyl-2-oxazoline) for ocular drug delivery of ciprofloxacin

Many formulation strategies have been employed to improve ocular bioavailability of topical eye drops. The aim of this study was to develop and evaluate a series of solid lipid nanoparticles coated with poly(2-ethyl-2-oxazoline) and chitosan for ocular delivery of ciprofloxacin. Ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) (PSLN) formulation was prepared by a combination of melt-emulsion sonication and low-temperature solidification methods. A Box-Behnken design, was employed to statistically optimize the effects of the amount of drug (X1), lipid:polymer ratio (X2) and surfactant concentration (X3) on particle size (Y1) and entrapment efficiency (Y2). Analysis of variance was used to validate the optimization design; and regression equations and response surface plots were generated. The optimized formulation was selected through numerical point prediction approach. These nanoparticles were characterized using dynamic light scattering, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). In vitro drug release and corneal permeation studies were carried out, while the mucoadhesive properties were evaluated ex vivo using porcine corneal tissue. The particle size and zeta potential of the optimized formulations ranged from 141.3 to 213.0 nm and +24.6 to −35.6 mV, respectively. PSLN possessed higher encapsulation efficiency than chitosan-coated solid lipid nanoparticles (CSLN). The in vitro drug release from all the formulations showed an initial burst release followed by prolonged release over 24 h. The release mechanism followed Korsemeyer-Peppas model and Fickian diffusion (n < 0.5). DSC revealed lower enthalpy and crystallinity of the formulations as also detected by PXRD, while TEM showed spherical particles in the lower nanometer range with a layer of polymer coating. The results of this study demonstrated that CSLN exhibited higher mucoadhesion and retention on corneal tissues compared with PSLN and also showed higher flux and apparent permeability, but with lower entrapment efficiency

Preliminary investigation of Dioclea reflexa seed gum as a food and potential pharmaceutical excipient

The chemical quality of natural gum determines its functionality and safe use. This study was to characterize some physicochemical properties and microbial load of gum obtained from Dioclea reflexa seed (DR), which has a history of folkloric use as a soup thickener in eastern Nigeria. The gum was extracted by aqueous maceration of DR. The microbial load was determined using the pour plate technique. The extract was screened for phytochemical constituents and analyzed for elemental content using atomic absorption spectroscopy (AAS) and scanning electron microscopy (SEM). Also, the morphology was viewed using SEM. The phytochemical screening indicated the presence of carbohydrates, starch, and simple sugars. The total viable aerobic bacterial and fungal counts were 2.0 x 101 and 1.0 x 100 (CFU/mL), respectively. The SEM micrograph showed that the polymer microstructure had dense and smooth surfaces, a property that has been associated with polysaccharides. The AAS elemental analysis showed the presence of several metals in the sample: Fe, Pb, Zn, Cd, Mg, Ca, and Na, in amounts generally within WHO permissible limits, except for Pb and Cd, whose levels were slightly above. The SEM analysis also showed the presence of K, Ca, Mg, Al, P, S, Na, and a preponderance of C and O. The presence of heavy metals could be associated with environmental pollution. DR gum's nature and chemical constituents present it as a potential food and pharmaceutical additive. Further studies should be done to validate the findings

Overcoming challenges in pediatric formulation with a patient-centric design approach: a proof-of-concept study on the design of an oral solution of a bitter drug

Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in‐use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in‐use stability protocols should be preferred in the stability evaluation of pediatric formulations.This work was supported by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., Portugal, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. This research was also supported by and Federal Government of Nigeria NEEDS Assessment grant‐2018. The authors are grateful to FCT (Portugal) for financial support by national funds FCT/MCTES to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and to the Associate Laboratory SusTEC (LA/P/0007/2020). Ítala M.G. Marx also acknowledges the Ph.D. research grant (SFRH/BD/137283/2018) provided by FCT.info:eu-repo/semantics/publishedVersio