Lung delivery of nanoliposomal salbutamol sulfate dry powder inhalation for facilitated asthma therapy

Abstract

The motive behind present work was to discover a solution for overcoming the problems allied with a deprived oral bioavailability of salbutamol sulfate (SS) due to its first pass hepatic metabolism, shorter half-life, and systemic toxicity at high doses. Pulmonary delivery provides an alternative route of administration to avoid hepatic metabolism of SS, moreover facilitated diffusion and prolonged retention can be achieved by incorporation into liposomes. Liposomes were prepared by thin film hydration technique using 3² full factorial design and formulation was optimized based on the vesicle size and percent drug entrapment (PDE) of liposomes. Optimized liposomal formulation exhibited an average size of about 167.2?±?0.170?nm, with 80.68?±?0.74% drug entrapment, and 9.74?±?1.10?mV zeta potential. The liposomal dispersion was then spray dried and further characterized for in-vitro aerosol performance using Andersen Cascade Impactor. Optimized liposomal formulation revealed prolonged in-vitro drug release of more than 90% up to 14?h following Higuchi’s controlled release model. Thus, the proposed new-fangled liposomal formulation would be a propitious alternative to conventional therapy for efficient and methodical treatment of asthma and alike respiratory ailments.     

Microparticulate Based Topical Delivery System of Clobetasol Propionate

Psoriasis is a chronic, autoimmune skin disease affecting approximately 2% of the world's population. Clobetasol propionate which is a superpotent topical corticosteroid is widely used for topical treatment of psoriasis. Conventional dosage forms like creams and ointments are commonly prefered for the therapy. The purpose of this study was to develop a new topical delivery system in order to provide the prolonged release of clobetasol propionate and to reduce systemic absorption and side effects of the drug. Clobetasol propionate loaded-poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by oil-in-water emulsion–solvent evaporation technique. Particle size analysis, morphological characterization, DSC and XRD analyses and in vitro drug release studies were performed on the microparticle formulations. Emulgel formulations were prepared as an alternative for topical delivery of clobetasol propionate. In vitro drug release studies were carried out from the emulgel formulations containing pure drug and drug-loaded microspheres. In addition, the same studies were performed to determine the drug release from the commercial cream product of clobetasol propionate. The release of clobetasol propionate from the emulgel formulations was significantly higher than the commercial product. In addition, the encapsulation of clobetasol propionate in the PLGA microspheres significantly delayed the drug release from the emulgel formulation. As a result, the decrease in the side effects of clobetasol propionate by the formulation containing PLGA microspheres is expected.     

Multiunit Floating Drug Delivery System of Rosiglitazone Maleate: Development, Characterization, Statistical Optimization of Drug Release and In Vivo Evaluation

A multiunit floating drug delivery system of rosiglitazone maleate has been developed by encapsulating the drug into Eudragit® RS100 through nonaqueous emulsification/solvent evaporation method. The in vitro performances of microspheres were evaluated by yield (%), particle size analysis, drug entrapment efficiency, in vitro floating behavior, surface topography, drug–polymer compatibility, crystallinity of the drug in the microspheres, and drug release studies. In vitro release was optimized by a {3, 3} simplex lattice mixture design to achieve predetermined target release. The in vivo performance of the optimized formulation was evaluated in streptozotocin-induced diabetic rats. The results showed that floating microspheres could be successfully prepared with good yields (69–75%), high entrapment (78-97%), narrow size distribution, and desired target release with the help of statistical design of experiments from very small number of formulations. In vivo evaluation in albino rats suggested that floating microspheres of rosiglitazone could be a promising approach for better glycemic control.     

Sustained-Release Delivery of Octreotide from Biodegradable Polymeric Microspheres

The study reports on the drug release behavior of a potent synthetic somatostatin analogue, octreotide acetate, from biocompatible and biodegradable microspheres composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular depot injection. The serum octreotide levels of three Oakwood Laboratories formulations and one Sandostatin LAR^® formulation were compared. Three formulations of octreotide acetate-loaded PLGA microspheres were prepared by a solvent extraction and evaporation procedure using PLGA polymers with different molecular weights. The in vivo drug release study was conducted in male Sprague–Dawley rats. Blood samples were taken at predetermined time points for up to 70 days. Drug serum concentrations were quantified using a radioimmunoassay procedure consisting of radiolabeled octreotide. The three octreotide PLGA microsphere formulations and Sandostatin LAR^® all showed a two-phase drug release profile (i.e., bimodal). The peak serum drug concentration of octreotide was reached in 30 min for all formulations followed by a decline after 6 h. Following this initial burst and decline, a second-release phase occurred after 3 days. This second-release phase exhibited sustained-release behavior, as the drug serum levels were discernible between days 7 and 42. Using pharmacokinetic computer simulations, it was estimated that the steady-state octreotide serum drug levels would be predicted to fall in the range of 40–130 pg/10 μL and 20–100 pg/10 μL following repeat dosing of the Oakwood formulations and Sandostatin LAR^® every 28 days and every 42 days at a dose of 3 mg/rat, respectively.     

Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles

The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148–337 d.nm, polydispersity index 0.04–0.45, drug entrapment 69–92%, and zeta potential in the range of −15 to −29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled (^99mTc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23–1.45, 258, and 61% for ^99mTc-DNP (i.n) compared to ^99mTc-DS (i.n) (0.38–1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.KEY WORDS: controlled release, nanoparticles, process optimization, scintigraphy     

Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization,in vitro and in vivo studies

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose, improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of −20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC_0–24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.     

Controlled Release of Dutasteride from Biodegradable Microspheres: In Vitro and In Vivo Studies

The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH), into poly(lactide-co-glycolide) (PLGA). A response surface method (RSM) with central composite design (CCD) was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods.     

In Vitro and In Vivo Evaluations of PLGA Microspheres Containing Nalmefene

Poor patient compliance, untoward reactions and unstable blood drug levels after the bolus administration are impeding the pharmacotherapy for insobriety. A long-acting preparation may address these limitations. The aim of this paper was to further investigate the in vitro characteristics and in vivo performances of nalmefene microspheres. Nalmefene was blended with poly (lactide-co-glycolide) (PLGA) to prepare the target microspheres by an O/O emulsification solvent evaporation method. The prepared microspheres exhibited a controlled release profile of nalmefene in vitro over 4 weeks, which was well fitted with a first-order model. In vitro degradation study showed that the drug release in vitro was dominated by both drug diffusion and polymer degradation mechanisms. Pharmacokinetics study indicated that the prepared microspheres could provide a relatively constant of nalmefene plasma concentration for at least one month in rats. The in vivo pharmacokinetics profile was well correlated with the in vitro drug release. Pharmacodynamics studies revealed that the drug loaded microspheres could produce a long-acting antagonism efficacy on rats. These results demonstrated the promising application of injectable PLGA microspheres containing nalmefene for the long-term treatment of alcohol dependence.     

Formulation optimization of chelerythrine loaded O-carboxymethylchitosan microspheres using response surface methodology

The aims of this investigation were to develop a procedure to prepare chelerythrine (CHE) loaded O-carboxymethylchitosan (O-CMCS) microspheres by emulsion cross-linking method and optimize the process and formulation variables using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The independent variables studied were O-CMCS/CHE ratio, O/W phase ratio, and O-CMCS concentration, dependent variables (responses) were drug loading content and encapsulation efficiency. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The process and formulation variables were optimized to achieve maximum drug loading content and entrapment efficiency by the desirability function. The optimized microsphere formulation was characterized for particle size, shape, morphology and in vitro drug release. Results for mean particle size, drug loading content, entrapment efficiency, and in vitro drug release of CHE-loaded O-CMCS microspheres were found to be of 12.18 μm, 4.16 ± 3.36%, 57.40 ± 2.30%, and 54.5% at pH 7.4 after 70 h, respectively. The combination use of RSM, BBD and desirability function could provide a promising application for O-CMCS as controlled drug delivery carrier and help to develop procedures for a lab-scale microemulsion process.     

Inulin-Based Tablet in Capsule Device for Variable Multipulse Delivery of Aceclofenac: Optimization and In Vivo Roentgenography

The aim of the study was to develop single-unit tablet in capsule system of aceclofenac for the treatment of late night pain and morning stiffness associated with rheumatoid arthritis. The system was conceptualized as a three-component design (1) a hard gelatin enteric-coated capsule (for carrying two pulses), (2) first-pulse granules (for rapid release in intestine), and (2) second-pulse matrix tablet (for slow release in colon). An appropriate integration of pH-sensitive (Eudragit S100) and bacteria-responsive (inulin) functions, on the basis of 3² factorial design, led to formulation of TICS 1–9 that were screened for in vitro release. TICS 2 with biphasic drug release of 98.64% from first-pulse granules in simulated intestinal fluid (12 h) and 97.82% from second-pulse matrix tablet in simulated colonic fluid (24 h) was the optimized formulation that exhibited Fickian diffusion of drug (n = 0.363). In vivo fluoroscopy in rats traced the intact tablet to colon in 7.5 h that got eroded at the tenth hour. This demonstrated the colon-specific delivery of the matrix tablet affirming the potential of the system to obviate the need for two-time administration of drug at odd hours. The experimental design was validated by extra design check point, and diffuse reflectance spectroscopy and DSC revealed absence of chemical interaction between the formulation excipients.KEY WORDS: aceclofenac, in vitro release, in vivo fluoroscopy, multipulse delivery, tablet in capsule system     

Thermally Triggered Mucoadhesive In Situ Gel of Loratadine: β-Cyclodextrin Complex for Nasal Delivery

The aim of the present study was to increase the solubility of an anti-allergic drug loratadine by making its inclusion complex with β-cyclodextrin and to develop it’s thermally triggered mucoadhesive in situ nasal gel so as to overcome first-pass effect and consequently enhance its bioavailability. A total of eight formulations were prepared by cold method and optimized by 2³ full factorial design. Independent variables (concentration of poloxamer 407, concentration of carbopol 934 P, and pure drug or its inclusion complex) were optimized in order to achieve desired gelling temperature with sufficient mucoadhesive strength and maximum permeation across experimental nasal membrane. The design was validated by extra design checkpoint formulation (F9) and Pareto charts were used to help eliminate terms that did not have a statistically significant effect. The response surface plots and possible interactions between independent variables were analyzed using Design Expert Software 8.0.2 (Stat Ease, Inc., USA). Faster drug permeation with zero-order kinetics and target flux was achieved with formulation containing drug: β-cyclodextrin complex rather than those made with free drug. The optimized formulation (F8) with a gelling temperature of 28.6 ± 0.47°C and highest mucoadhesive strength of 7,676.0 ± 0.97 dyn/cm² displayed 97.74 ± 0.87% cumulative drug permeation at 6 h. It was stable for over 3 months and histological examination revealed no remarkable damage to the nasal tissue.     

Preparation and characterization of poly (lactic-co-glycolic acid) nanofibers containing simvastatin coated with hyaluronic acid for using in periodontal tissue engineering

Periodontal diseases can lead to soft tissue defects. Tissue engineering can provide functional replacements for damaged tissues. Recently, electrospun nanofibers have attracted great interest for tissue engineering and drug delivery applications. This has been revealed that statins exhibit positive impacts on the proliferation and regeneration of periodontal tissues. Electrospun simvastatin loaded poly (lactic-co-glycolic acid) (SIM-PLGA-NF) were prepared using electrospinning technique. Optimal conditions for preparation of SIM-PLGA-NF (PLGA concentration of 30 wt%, voltage of 15 kV, and flow rate of 1.5 ml h⁻¹) were identified using a 2³ factorial design. The optimized SIM-PLGA-NFs (diameter of 640.2 ± 32.5 nm and simvastatin entrapment efficacy of 99.6 ± 1.5%) were surface modified with 1% w/v hyaluronic acid solution (1%HA- SIM-PLGA-NF) to improve their compatibility with fibroblasts and potential application as a periodontal tissue engineering scaffold. HA-SIM-PLGA NFs were analyzed using SEM, FTIR, and XRD. 1%HA-SIM-PLGA-NF had uniform, bead-free and interwoven morphology, which is similar to the extracellular matrix. The mechanical performance of SIM-PLGA-NFs and release profile of simvastatin from these nanofibers have been also greatly improved after coating with HA. In vitro cellular tests showed that the proliferation, adhesion, and differentiation of fibroblast cells positively enhanced on the surface of 1%HA- SIM-PLGA-NF. These results demonstrate the potential application of 1%HA-SIM-PLGA-NFs as a scaffold for periodontal tissue engineering.     

Optimized Ciclopirox-Based Eudragit RLPO Nail Lacquer: Effect of Endopeptidase Enzyme as Permeation Enhancer on Transungual Drug Delivery and Efficiency Against Onychomycosis

The aims of our investigation were to develop and optimize ciclopirox (CPX) nail lacquer using nonbiodegradable Eudragit RLPO (E-RLPO) as a film former and to assess its penetration efficiency across the human nail plate. Preliminary trials such as hydration enhancement factor (HEF), a retained drug in the nail plate, and SEM were studied to select the optimized permeation enhancer to be incorporated in the optimized lacquer formulation. A 3³ full factorial design was built up to study the effect of three different factors, concentration of E-RLPO (10, 20, and 30%), Tween 80 (0.25, 0.5, and 1%), and triacetin (0, 10, and 30% of polymer weight). The studied responses were the drying time, water resistance, viscosity, and drug release up to 4 h. An ex vivo permeation study for the optimized formulations was carried out. The preliminary study aided the selection of 5% papain (endopeptidase enzyme) as a penetration enhancer; it showed the highest HEF of 15.27%, the highest amount of drug retained in the nail plate (886.2 μg/g). An ex vivo permeation study guided the selection of F4B (flux value of 3.79 μg/cm²/h) as optimized formulation. The optimized lacquer formula showed threefold increases in the permeation than the marketed CPX lacquer (Batrafen®). Confocal laser scanning microscopy revealed the higher intensity of the Rhodamine B dye across the nail plate in the case of the formula containing papain than the marketed formula without papain. Conclusively, an efficient and stable nail lacquer was developed for potential transungual delivery of CPX to target the drug to the nail bed and ensure efficiency against onychomycosis.     

Statistical Design for Formulation Optimization of Hydrocortisone Butyrate-Loaded PLGA Nanoparticles

The aim of this investigation was to develop hydrocortisone butyrate (HB)-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) with ideal encapsulation efficiency (EE), particle size, and drug loading (DL) under emulsion solvent evaporation technique utilizing various experimental statistical design modules. Experimental designs were used to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. Plackett–Burman design for independent variables was first conducted to prescreen various formulation and process variables during the development of NP. Selected primary variables were further optimized by central composite design. This process leads to an optimum formulation with desired EE, particle size, and DL. Contour plots and response surface curves display visual diagrammatic relationships between the experimental responses and input variables. The concentration of PLGA, drug, and polyvinyl alcohol and sonication time were the critical factors influencing the responses analyzed. Optimized formulation showed EE of 90.6%, particle size of 164.3 nm, and DL of 64.35%. This study demonstrates that statistical experimental design methodology can optimize the formulation and process variables to achieve favorable responses for HB-loaded NP.     

Tri-block co-polymer nanocarriers for enhancement of oral delivery of felodipine: preparation,in vitro characterization and ex vivo permeation

This study aimed to prepare, optimize and characterize novel felodipine-loaded polymeric nanomicelles, using a pluronic mixture of F127 and P123. Thin-film hydration method was adopted for the preparation of different polymeric nanomicelles (T1–T12) according to a 4¹.3¹ full factorial design. Factors studied were: Pluronic®:drug ratio (P:D ratio) (10, 20, 30 and 40?w/w) and percent of hydrophilic polymer (F127%) (33.33%, 50% and 66.67% w/w). Optimization criteria were to maximize transmittance percent (T%) and entrapment efficiency percent (EE%) and to minimize particle size (PS) and polydispersity index (PDI). The optimized formulation was further characterized by DSC, FTIR and ¹H NMR studies. It was also subjected to stability testing and ex vivo permeation using rabbit intestines. Spherical nanomicelles of particle size ranging from 26.18 to 87.54?nm were successfully obtained. The optimized formulation was found to be the already prepared formulation T12 (P:D ratio of 40 and 66.67% F127) with suitable T% and EE% of 95.12% and 91.75%, respectively. DSC, FTIR and ¹H NMR studies revealed felodipine (FLD) incorporation within T12 nanomicelles. T12 enhanced the ex vivo intestinal permeation of FLD when compared to a drug suspension and showed good stability. Therefore, pluronic nanomicelles could be promising for improved oral delivery of FLD.     

Preparation and characterization of poly(D,L-lactide-co-glycolide) microspheres for controlled release of human growth hormone

The purpose of this research was to assess the physicochemical properties of a controlled release formulation of recombinant human growth hormone (rHGH) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) composite microspheres. rHGH was loaded in poly(acryloyl hydroxyethyl) starch (acHES) microparticles, and then the protein-containing microparticles were encapsulated in the PLGA matrix by a solvent extraction/evaporation method. rHGH-loaded PLGA microspheres were also prepared using mannitol without the starch hydrogel microparticle microspheres for comparison. The detection of secondary structure changes in protein was investigated by using a Fourier Transfer Infrared (FTIR) technique. The composite microspheres were spherical in shape (44.6±2.47 μm), and the PLGA-mannitol microspheres were 39.7±2.50 μm. Drug-loading efficiency varied from 93.2% to 104%. The composite microspheres showed higher overall drug release than the PLGA/mannitol microspheres. FTIR analyses indicated good stability and structural integrity of HGH localized in the microspheres. The PLGA-acHES composite microsphere system could be useful for the controlled delivery of protein drugs.     

Selective Interactions of Zein Microspheres with Different Class of Drugs: An In Vitro and In Silico Analysis

In this study, we have evaluated the interactions of zein microspheres with different class of drugs (hydrophobic, hydrophilic, and amphiphilic) using in vitro and in silico analysis. Zein microspheres loaded with aceclofenac, metformin, and promethazine has been developed by solvent evaporation technique and analyzed for its compatibility. The physical characterization depicted the proper encapsulation of hydrophobic drug in the microspheres. The in vitro release study revealed the sustaining ability of the microspheres in the following order: hydrophobic > hydrophilic > amphiphilic. In silico analysis also confirmed the better binding affinity and greater interactions of hydrophobic drug with zein. The above results revealed that zein is more suitable for hydrophobic drugs in the development of sustained drug delivery systems using solvent evaporation technique. The study therefore envisages a scope for identifying the most suitable polymer for a sustained drug delivery system in accordance with the nature of the drug.KEY WORDS: hydrophilic drugs, hydrophobic drugs, in silico analysis, protein-drug interactions, solvent evaporation, zein microspheres     

Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> Evaluation,and <Emphasis Type="Italic">Ex Vivo</Emphasis> Assessment

Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2–4% w/v and 0–40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 μg cm^?2 drug retention in the skin, 44.312 μg cm^?2 h^?1 drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation.     

Dopamine‐loaded poly(d,l‐lactic‐co‐glycolic acid) microspheres: New strategy for encapsulating small hydrophilic drugs with high efficiency

The effective controlled release of small hydrophilic drugs from poly(d ,l ‐lactic‐co‐glycolic acid) (PLGA) microspheres has remained a challenge, largely due to the difficulty of loading a large amount of the drug inside the microspheres, owing to the hydrophilicity of the drugs. This study provides a new strategy for increasing encapsulation of small hydrophilic drugs inside PLGA microspheres by utilizing noncovalent, physical adsorption between hydrophilic drugs and emulsifying polymers of poly(vinyl alcohol) and pluronic. An order of magnitude increase in drug loading efficiency from 2.7 to 18.6% for dopamine, a model small hydrophilic drug, was achieved. The large amount of dopamine‐loaded PLGA formulation herein could be useful for the treatment of Parkinson's disease. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:215–223, 2014     

A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluations

Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20–25 μm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit’s eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye.