Mucoadhesive liposomes as ocular delivery system: physical,microbiological, and in vivo assessment

Background: Mucoadhesive drug delivery is a promising strategy to overcome ocular biopharmaceutical constraints. Objective and methods: Ciprofloxacin HCl-loaded reverse phase evaporation liposomes were coated with different concentrations and molecular weights of mucoadhesive biocompatible chitosan polymer to form chitosomes. This colloidal mucoadhesive system was evaluated in vitro and in vivo with respect to deliver the antibiotic to ocular surface. Results and conclusion: The results obtained pointed out that liposome coating process resulted in entrapment efficiency reduction and higher chitosan concentration, and molecular weight showed a more pronounced effect. No morphological differences between coated and uncoated liposomes were observed. Diffusion was the drug release mechanism from chitosomes. Concerning rheological behavior, pseudoplastic flow was characteristic to the prepared chitosomal dispersions. In addition, chitosan coating improved the ocular permeation of ciprofloxacin HCl. Microbiologically; this formulated system enhanced antimicrobial activity of ciprofloxacin HCl against both Gram-positive and Gram-negative bacteria. Moreover, this mucoadhesive system was able to inhibit the growth of Pseudomonas aeruginosa in rabbits' eyes for 24 hours when compared to the marketed preparation. In vivo bacterial conjunctivitis model elucidated that symptoms were controlled by the prolonged release formulation such as that done by the marketed product.     

Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.

Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization.

Results: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12?h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin.

Conclusion: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.     

Interaction pattern and in vitro,in vivo release behavior of simvastatin-loaded chitosan nanoformulation

Abstract

Objective and methods: This study predicted the nature of chitosan interactions and effects of this interaction on drug release mechanism in simvastatin-loaded chitosan nanoformulation using molecular docking, spectroscopic and thermal analysis.

Significance: This work explains in depth the molecular mechanism of simvastatin and chitosan bond formation in nanoformulation.

Results: The effective encapsulation and sustain release properties of chitosan were indicated by increase in melting endotherm of simvastatin. Intermolecular hydrogen bond between third hydroxyl group pyranone ring of simvastatin and amino group of chitosan represented the stability of active lactone moiety that was not cleaved during formulation which is prerequisite for biological activity. UV–vis spectroscopic characterization, shift in infrared vibration wavenumber of simvastatin and chitosan, ligand titration, 1HNMR and 13C-NMR analyses confirmed this interaction pattern. The pharmacokinetic evaluation in mouse model revealed the sustain release property of nanoformulation.

Conclusion: Thus formation of intermolecular hydrogen bond in nanoformulation contributed to modified physicochemical properties and improved in vivo performance of simvastatin.     

Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan

Context: Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping.

Objective: Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine.

Methods: Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release.

Results: Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product.

Conclusion: Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release.     

New nanomicelle curcumin formulation for ocular delivery: improved stability,solubility, and ocular anti-inflammatory treatment

Context: A stable topical ophthalmic curcumin formulation with high solubility, stability, and efficacy is needed for pharmaceutical use in clinics.

Objectives: The objective of this article was to describe a novel curcumin containing a nanomicelle formulation using a polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol (PVCL–PVA–PEG) graft copolymer.

Methods: Nanomicelle curcumin was formulated and optimized and then further evaluated for in vitro cytotoxicity/in vivo ocular irritation, in vitro cellular uptake/in vivo corneal permeation, and in vitro antioxidant activity/in vivo anti-inflammatory efficacy.

Results: The solubility, chemical stability, and antioxidant activity were greatly improved after the encapsulation of the PVCL–PVA–PEG nanomicelles. The nanomicelle curcumin ophthalmic solution was simple to prepare and the nanomicelles are stable to the storage conditions, and it had good cellular tolerance. Nanomicelle curcumin also had excellent ocular tolerance in rabbits. The use of nanomicelles significantly improved in vitro cellular uptake and in vivo corneal permeation as well as improved anti-inflammatory efficacy when compared with a free curcumin solution.

Conclusions: These findings indicate that nanomicelles could be promising topical delivery systems for the ocular administration of curcumin.     

In-vitro and in-vivo evaluation of ciprofloxacin liposomes for pulmonary administration

Objective: The aim of this study was to investigate the ciprofloxacin liposome of high encapsulation efficiency with optimal physical properties for pulmonary administration and to test its in-vivo potential in rats.

Methods: Ciprofloxacin-loaded liposome was prepared by gradient of ammonium sulfate method. The particle size and morphology were determined using a NANOPHOX particle size analyzer and a transmission electron microscope, respectively. Encapsulation efficiency was calculated by UV spectrophotometry. Ciprofloxacin liposome released in vitro was performed using simulated lung fluid. In-vivo studies, pharmacokinetics and pulmonary distribution, HPLC method was established to determine the concentration of ciprofloxacin in rat plasma and lung tissue. The pulmonary pathological section was used to observe the change of pulmonary pathology.

Results: The optimized ciprofloxacin liposome, which had a high encapsulation efficiency of 93.96%, and an average particle size of 349.6?nm with a span of 0.42, showed sustained in-vitro release. The optimized ciprofloxacin liposome was further examined in the in-vivo study in rats. The concentration of ciprofloxacin in lung and blood was simultaneously determined in each rat. The ratio of the AUC_lung value between ciprofloxacin liposome and ciprofloxacin solution was 288.33, whereas the relative bioavailability was 72.42%, and the drug targeting efficiency of ciprofloxacin liposome and ciprofloxacin solution by intratracheal administration were 799.71 and 2.01, respectively.

Conclusion: Ciprofloxacin liposome for pulmonary administration offered an attractive alternative that was able to deliver high concentrations of antibiotic directly to the chosen target site while minimizing the local irritation.     

Implementation of two different experimental designs for screening and optimization of process parameters for metformin-loaded carboxymethyl chitosan formulation

Abstract

Metformin (MET) was effectively encapsulated into O-carboxymethyl chitosan (O-CMC) polymeric formulation using an experimental design method. Six factors Plackett–Burman (PB) design was utilized to find the significant process parameters. Linear equations used to study the effect of each process parameters on particle size (PS), encapsulation efficiency (EE), and zeta potential (ZP) and the most influential three factors decided for further optimization. Optimization was carried out by implementing three-factor three-level Box–Behnken (BB) design. Mathematical models were generated by regression analysis for responses of PS, EE, and ZP. Two-step experimental design took into account for the preparation of optimized formulation with maximum %EE (72.78?±?9.7%) and minimum PS (225.67?±?5.53?nm) at optimum process conditions with a ZP of –5.22?mV for the nano-polymeric formulation in an economical matter by reduction chemical use and formulation time. Furthermore, the biological activity of the final formulation was determined by in vitro cytotoxicity study compared to free MET. The cytotoxicity result reveals that both pure drug and nano-formulation biocompatible with MCF10A non-tumorigenic cell line and lethal for the MCF7 cell line. These in vitro results were the first helpful step to further investigate O-CMC loaded MET nanoparticles in diagnostic and therapeutic applications of breast cancer.     

Chitosan–silver oxide nanocomposite film: Preparation and antimicrobial activity

The chitosan–silver oxide encapsulated nanocomposite film was prepared by solution casting method. The prepared film was characterized by FTIR, scanning electron microscopy (SEM), thermal studies, and UV-Vis spectroscopy. The elemental composition of the film was studied by energy dispersive X-ray analysis (EDAX). The antibacterial activity of the composite film against pathogenic bacteria viz. Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa was measured by agar diffusion method. Our observations suggest that chitosan as biomaterial based nanocomposite film containing silver oxide has an excellent antibacterial ability for food packaging applications.     

Development of a topical mupirocin spray for antibacterial and wound-healing applications

Objective: The aim of this study was to develop mupirocin topical spray using Eudragit E100 as a film-forming agent for the treatment of bacterial skin infections as well as to promote wound healing.

Materials and methods: Twenty-seven of mupirocin formulations were formulated containing Eudragit E100 and other excipients. Mupirocin spray was prepared by aerosol crimping and filling machine using HFA-134a as a propellant. The formulations were evaluated for their stability and physicochemical properties. The factorial study was applied to evaluate the effects of glycerol and PEG400 on mupirocin-loaded Eudragit E100 films. The optimized formulation was assessed of drug release, antibacterial activities and in vitro cell line studies in comparison to the ointment formulation.

Results and discussion: Mupirocin sprays were formulated and optimized to obtain the formulation with excellent physicochemical and mechanical properties of the dressing film. The formulation had an excellent stability up to a year with more than 80% of mupirocin content. Mupirocin was released from the film up to 90% within 2?h. The formulation had a potent antibacterial effect against S. aureus and S. epidermidis. The formulation was safe to use as a topical formulation that had no toxicity to keratinocytes, fibroblasts and monocytes. The formulation also had an antiendotoxin effect without stimulating the production of NO and inflammatory cytokines (IL-1β and TNF-α).

Conclusions: Mupirocin topical spray was successful developed as a topical formulation and can be used instead of the ointment formulation. Animal experiments are warranted to further emphasize the safe use in the human skin.     

Facile development,characterization, and optimization of new metformin-loaded nanocarrier system for efficient colon cancer adjunct therapy

Purpose: Metformin hydrochloride (MF) repurposing as adjuvant anticancer therapy for colorectal cancer (CRC) proved effective. Several studies attempted to develop MF-loaded nanoparticles (NPs), however the entrapment efficiency (EE%) was poor. Thus, the present study aimed at the facile development of a new series of chitosan (CS)-based semi-interpenetrating network (semi-IPN) NPs incorporating Pluronic^® nanomicelles as nanocarriers for enhanced entrapment and sustained release of MF for efficient treatment of CRC.

Methods: The NPs were prepared by ionic gelation and subsequently characterized using FTIR, DSC, TEM, and DLS. A full factorial design was also adopted to study the effect of various formulation variables on EE%, particle size, and zeta-potential of NPs.

Results: NPs had a spherical shape and a mean particle size ranging between 135 and 220?nm. FTIR and DSC studies results were indicative of successful ionic gelation with the drug being dispersed in its amorphous form within CS-Pluronic^® matrix. Maximum EE% reaching 57.00?±?12.90% was achieved using Pluronic^®-123 based NPs. NPs exhibited a sustained release profile over 48?h. The MF-loaded NPs sensitized RKO CRC cells relative to drug alone.

Conclusion: The reported results highlighted the novel utility of the developed NPs in the arena of colon cancer treatment.     

Synthesis,in vitro characterization,and anti-tumor effects of novel polystyrene-poly(amide-ether-ester-imide) co-polymeric micelles for delivery of docetaxel in breast cancer in Balb/C mice

Objective: The goal of the present work was to make novel co-polymeric micellar carriers for the delivery of docetaxel (DTX).

Significance: Co-polymeric micelles can not only solubilize DTX and eliminate the need for toxic surfactants to dissolve it, but also cause passive targeting of the drug to the tumor and reduce its toxic side effects.

Methods: Poly(styrene-maleic acid) (SMA) was conjugated to poly (amide-ether-ester-imide)-poly ethylene glycol (PAEEI-PEG). Copolymer synthesis was proven by Fourier transform infrared (FTIR) and ¹H-nuclear magnetic resonance (¹H-NMR). The SMA-PAEEI-PEG micelles loaded with DTX were prepared and their critical micelle concentration (CMC), zeta potential, particle size, entrapment efficiency, and their release efficiency were studied. MCF-7 and MDA-MB231 breast cancer cells were used to evaluate the cellular uptake and cytotoxicity of the micelles. The antitumor activity of the DTX-loaded nanomicelles was measured in Balb/c mice.

Results: The FTIR and HNMR spectroscopy confirmed successful conjugation of SMA and PAEEI-PEG. The drug loading efficiency was in the range of 34.01–72.75% and drug release lasted for 120?h. The CMC value of the micelles was affected by the SMA/PAEEI-PEG ratio and was in the range of 29.85–14.28?µg/ml. The DTX-loaded micelles showed five times more cytotoxicity than the free drug. The DTX loaded micelles were more effective in tumor growth suppression in vivo and the animals showed an enhanced rate of survival.

Conclusion: The results show that the SMA-PAEEI-PEG micelles of DTX could potentially provide a suitable parenteral formulation with more stability, higher cytotoxicity, and improved antitumor activity.     

Improvement of bone microarchitecture in methylprednisolone induced rat model of osteoporosis by using thiolated chitosan-based risedronate mucoadhesive film

Objective: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis.

Significance: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy.

Methods: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption.

Results: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation.

Conclusions: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis.     

Taste masking of azithromycin by resin complex and sustained release through interpenetrating polymer network with functionalized biopolymers

Abstract

Objective: The objective was to evaluate taste masking of azithromycin (AZI) by ion exchange resins (IERs) and the formation of covalent semi interpenetrating polymer network (IPN) beads using chitosan (CS) and sodium carboxylated agarose (SCAG) for sustained release of drug.

Methods: Methacrylic acid (MAA)-based IERs were prepared by suspension polymerization method. Drug release complexes (DRCs) were prepared by different drug:resin ratios i.e. 1:1, 1:2 and 1:4. The resultant DRCs were characterized using DSC, FTIR, PXRD, in vivo and in vitro taste masking, and in vitro drug release at gastric pH. IPN beads were prepared by entrapping DRCs with bio polymers and cross linked with trisodium citrate (NaCIT), and further cross-linked with glutaraldehyde (GA) for sustained release of AZI.

Results: In vitro and in vivo taste masking studies showed that MD1:4 DRC formulation was optimal. The release of AZI from DRC was found to be very fast at gastric pH i.e. 97.37?±?1.02% within 45?min. The formation of IPN beads was confirmed by FTIR. The release of drug from IPN beads at gastric and intestinal pH was found to be “<28% and <60%”, respectively. The release kinetics showed Fickian diffusion profile for ionically cross-linked beads and zero-order release mechanism for GA cross-linking beads.

Conclusions: DRCs can be effectively used for taste masking and newly formulated IPN beads demonstrated sustained release of AZI.     

Optimization and characterization of tannic acid loaded niosomes for enhanced antibacterial and anti-biofilm activities

The purpose of this study was to prepare and characterize an optimized system of tannic acid-loaded niosomes as a potential carrier for antibacterial and anti-biofilm delivery. The niosomal formulation was optimized using response surface methodology (RSM). The effects of the molar ratio of surfactant to cholesterol, drug concentration, and molar ratio of Span 60 to Tween 60 on particle size and drug entrapment efficiency of the niosomal nanocarrier were studied. The optimized nanoparticles were characterized in terms of the morphology, in vitro release profile, and antibacterial properties. Moreover, Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) techniques were utilized to investigate drug-excipient interactions. Antibacterial and anti-biofilm activities of free tannic acid and tannic acid-loaded niosome were investigated against selected pathogenic bacteria including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus. Furthermore, the expression level of biofilm-associated genes was evaluated in selected pathogenic bacteria using Real-Time PCR. According to the results, the dependent variables (particle size and entrapment efficiency) were best fitted to the quadratic model. The particle size and entrapment efficiency of the best niosomal formulation were 89 nm and 82%, respectively. The in vitro release of the optimized formulation showed a controlled release profile. Release kinetics indicated a diffusion-based release of the drug. FTIR and DSC studies also confirmed the absence of drug-excipient interactions. The optimized formulation exhibited higher antibacterial effects as compared with the free drug solution. Moreover, the time-kill assay of the encapsulated drug revealed a slow and controlled inhibition of bacterial growth for 72 h while the free drug was used up in the first hours. Moreover, tannic acid-loaded niosome reduced biofilm formation capacity in selected strains and down-regulated the biofilm gene expression as compared to free tannic acid.The optimized formulation containing tannic acid can be a promising candidate for designing a new delivery system for this antibacterial and anti-biofilm agent.     

Intradermal and follicular delivery of adapalene liposomes

Abstract

Background: Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance.

Objective: To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties.

Methods: A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles.

Results: The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66?±?3.5?nm in diameter and encapsulation efficiency of 97.01?±?1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72?±?0.83?μg/cm²) in hair follicles than gel (3.33?±?0.26?μg/cm²) and drug solution (1.62?±?0.054?μg/cm²). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation.

Conclusion: Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.     

Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel

Objective: This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.

Significance: PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.

Methods: Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box–Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.

Results: The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160?mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS?=?2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37?°C. The optimized hydrogel formulation consisted of HPMC solution (103.69?mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100?mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.

Conclusions: NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.     

Low molecular weight chitosan-based conjugates for efficient Rhein oral delivery: synthesis,characterization, and pharmacokinetics

Objective: This article aims to design low molecular weight chitosan (LMWC)-based conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved solubility and enhanced bioavailability.

Significance: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability.

Methods: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and ¹H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35?mg/kg for pharmacokinetic studies in Sprague Dawley rats.

Results: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73?mg/mL, which exhibited a sustained release pattern over 72?h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T_1/2 and AUC_0–∞, respectively, as compared to RH suspension.

Conclusion: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery.     

Development,optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box–Behnken experimental design

Objective: The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs).

Methods: Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett–Burman design (PBD) followed by Box–Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP.

Results: The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39?±?1.82?nm, apparent drug content (ADC) of 72.06?±?0.86%, and zeta potential (ZP) of ?13.91?±?1.21?mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48?h and followed Korsmeyer–Peppas release kinetic model.

Conclusions: A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.     

Chitosan Matrix Tablets: The Influence of Excipients on Drug Release

Abstract

The influence of excipients on drug release from chitosan matrix tablets was investigated, using diltiazem hydrochloride as model drug. Tablets were prepared by direct compression and the effect of different concentrations of the excipients lactose, sodium lauryl sulphate, sodium alginate, carbopol 934, citric acid and hydroxypropylmethyl-cellulose on drug release profiles was studied. Sustained release of the drug was obtained in all cases but the results indicate that both type and amount of excipient used influences drug release rate. The results support the idea that chitosan can be suitable as a basis for sustained release matrix tablets, and that drug release rate can be influenced by the addition of excipients. It is possible to make use of the interaction between chitosan and excipients in the formulation to provide further prolongation of release.     

Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain

Abstract

Objective: Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer’s disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined.

Methods: Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25?°C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1?h after administration using fluorescence microscopy and software-aided image processing.

Results: Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190?nm, and a zeta potential of +40.4 and +31.6?mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07%?±?6.67 after 72?h), improved formulation stability at 4?°C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p?>?0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices.

Conclusion: Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer’s disease management.