Chitosan Nanoparticles with Encapsulated Natural and UF-Purified Annatto and Saffron for the Preparation of UV Protective Cosmetic Emulsions.

The aim of the present work is to evaluate the preparation of sunscreen emulsions based on chitosan (CS) nanoparticles with annatto, ultrafiltrated (UF) annatto, saffron, and ultrafiltrated saffron. Ionic gelation was used for the preparation of chitosan nanoparticles, while their morphological characteristics and physicochemical properties were evaluated via Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), and dynamic light scattering (DLS). Results showed that the prepared nanoparticles ranged from ~150 to ~500 nm and had a spherical or irregular shape. In the case of annatto and UF annatto, due to the formation of H-bonds, the sunscreen agents were amorphously dispersed within CS nanoparticles, while in the case of saffron and UF saffron, crystalline dispersion was observed. All encapsulated materials had good thermal stability as well as color stability. In a further step, sunscreen emulsions were prepared based on the formed CS-sunscreen nanoparticles and evaluated for their stability in terms of pH and viscosity, along with their ultraviolet (UV) radiation protection ability in terms of sun protection factor (SPF). All prepared emulsions showed low cytotoxicity and good storage stability for up to 90 days, while minimum sunscreen protection was observed with SPF values varying from 2.15 to 4.85.

Poly(Lactic Acid) Block Copolymers with Poly(Hexylene Succinate) as Microparticles for Long-Acting Injectables of Risperidone Drug.

In the present work, Risperidone microparticles from poly(lactic acid)/poly(hexylene succinate) (PLA-b-PHSu) block copolymers in different ratios, 95/05, 90/10 and 80/20 w/w, were examined as long-acting injectable formulations. Nuclear magnetic resonance (NMR) was used to verify the successful synthesis of copolymers. Enzymatic hydrolysis showed an increase in weight loss as the content of PHSu increased, while the cytotoxicity studies confirmed the biocompatibility of the copolymers. The polyesters were further used to encapsulate Risperidone by spray drying. The drug-loaded microparticles were studied by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray diffraction (XRD). SEM microphotographs confirmed that spherically shaped microparticles were prepared with sizes about 5-12 µm, while XRD and differential scanning calorimetry (DSC) studies evidenced that Risperidone was encapsulated in amorphous form. The drug loading and the entrapment efficiency of Risperidone were studied as well as the in vitro release from the prepared microparticles. As the content of PHSu increased, a higher release of Risperidone was observed, with PLA-b-PHSu 80/20 w/w succeeding to release 100% of RIS within 12 days. According to theoretical modeling, the kinetics of RIS release from PLA-b-PHSu microparticles is complex, governed by both diffusion and polymer erosion.

Intravitreal Administration Effect of Adipose-Derived Mesenchymal Stromal Cells Combined with Anti-VEGF Nanocarriers, in a Pharmaceutically Induced Animal Model of Retinal Vein Occlusion.

Antiangiogenic therapeutic agents (anti-VEGF) have contributed to the treatment of retinal vein occlusion (RVO) while mesenchymal stromal cell- (MSCs-) mediated therapies limit eye degeneration. The aim of the present study is to determine the effect of adipose-derived MSCs (ASCs) combination with nanocarriers of anti-VEGF in a pharmaceutically induced animal model of RVO. Nanoparticles (NPs) of thiolated chitosan (ThioCHI) with encapsulated anti-VEGF antibody were prepared. ASCs were isolated and genetically modified to secrete the green fluorescence GFP. Twenty-four New Zealand rabbits were divided into the I-IV equal following groups: ASCs, ASCs + nanoThioCHI-anti-VEGF, RVO, and control. For the RVO induction, groups I-III received intravitreal (iv) injections of MEK kinase inhibitor, PD0325901. Twelve days later, therapeutic regiments were administered at groups I-II while groups III-IV received BSS. Two weeks later, the retinal damage evaluated via detailed ophthalmic examinations, histological analysis of fixed retinal sections, ELISA for secreted cytokines in peripheral blood or vitreous fluid, and Q-PCR for the expression of related to the occlusion and inflammatory genes. Mild retinal edema and hemorrhages, limited retinal detachment, and vasculature attenuation were observed in groups I and II compared with the pathological symptoms of group III which presented a totally disorganized retinal structure, following of positive immunostaining for neovascularization and related to RVO markers. Important reduction of the high secreted levels of inflammatory cytokines was quantified in groups I and II vitreous fluid, while the expression of the RVO-related and inflammatory genes has been significantly decreased especially in group II. GFP+ ASCs, capable of being differentiated towards neural progenitors, detected in dissociated retina tissues of group II presenting their attachment to damaged area. Conclusively, a stem cell-based therapy for RVO is proposed, accompanied by sustained release of anti-VEGF, in order to combine the paracrine action of ASCs and the progressive reduction of neovascularization.

L-Cysteine Modified Chitosan Nanoparticles and Carbon-Based Nanostructures for the Intranasal Delivery of Galantamine.

The present study evaluates the use of thiolized chitosan conjugates (CS) in combination with two fundamental carbon nanoforms (carbon dots (CDs) and Hierarchical Porous Carbons (HPC)) for the preparation of intranasally (IN) administrated galantamine (GAL) nanoparticles (NPs). Initially, the modification of CS with L-cysteine (Cys) was performed, and the successful formation of a Cys-CS conjugates was verified via 1H-NMR, FTIR, and pXRD. The new Cys-CS conjugate showed a significant solubility enhancement in neutral and alkaline pH, improving CS's utility as a matrix-carrier for IN drug administration. In a further step, drug-loaded NPs were prepared via solid-oil-water double emulsification, and thoroughly analyzed by SEM, DLS, FTIR and pXRD. The results showed the formation of spherical NPs with a smooth surface, while the drug was amorphously dispersed within most of the prepared NPs, with the exemption of those systems contianing the CDs. Finally, in vitro dissolution release studies revealed that the prepared NPs could prolong GAL's release for up to 12 days. In sum, regarding the most promising system, the results of the present study clearly suggest that the preparation of NPs using both Cys-CS and CDs results in a more thermodynamically stable drug dispersion, while a zero-order release profile was achieved, which is essential to attain a stable in vivo pharmacokinetic behavior.

Leflunomide Loaded Chitosan Nanoparticles for the Preparation of Aliphatic Polyester Based Skin Patches.

In the present study, the preparation of controlled-released leflunomide (LFD)-loaded skin patches was evaluated, utilizing the combination of chitosan (CS) nanoparticles (NPs) incorporated into suitable poly(l-lactic acid) (PLLA) or poly(lactic-co-glycolic acid) (PLGA) polyester matrices. Initially, LFD-loaded CS NPs of ~600 nm and a smooth surface were prepared, while strong inter-molecular interactions between the drug and the CS were unraveled. In the following step, the prepared LFD-loaded CS NPs were incorporated into PLLA or PLGA, and thin-film patches were prepared via spin-coating. Analysis of the prepared films showed that the incorporation of the drug-loaded CS NPs resulted in a significant increase in the drug's release rate and extent as compared to neat LFD-loaded polyester patches (i.e., prepared without the use of CS NPs). In-depth analysis of the prepared formulations showed that the amorphization of the drug within the matrix and the increased wetting properties of the prepared CS NPs were responsible for the improved thin-film patch characteristics.

Leflunomide Sustained Skin Delivery Based on Sulfobetaine-Modified Chitosan Nanoparticles Embedded in Biodegradable Polyesters Films.

The aim of the present study was to prepare a leflunomide (LFD) sustained release transdermal delivery system for the treatment of psoriasis. In this context, LFD-loaded nanoparticles (NPs) based on either neat chitosan (CS) or CS modified with [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SDAEM, a sulfobetaine zwitterionic compound) were initially prepared via ionotropic gelation and characterized in terms of in vitro dissolution, physicochemical, and antibacterial properties. Results showed that the use of the SDAEM-modified CS resulted in the formation of LFD-loaded NPs with improved wetting and solubilization properties, better in vitro dissolution profile characteristics (i.e., higher dissolution rate and extent), and improved (enhanced) antibacterial properties. The resultant LFD-loaded NPs were then embedded in suitable thin-film skin patches, prepared via spin-coating, utilizing two different biodegradable polyesters, namely methoxy polyethylene glycol-b-poly(L-lactide) (mPEG-b-PLA, at a ratio of 25/75 mPEG to PLA) and poly(lactic-co-glycolic acid) (PLGA at a ratio of 75/25 DL-lactide/glycolide copolymer). Results showed the formation of polymeric thin-films with no agglomeration (or trapped air) and uniform structure in all cases, while the LFD-loaded NPs were successfully embedded in the polymeric matrix. Analysis of the obtained in vitro dissolution profiles revealed a sustained release profile of the drug for up to approximately twelve days, while between the two proposed systems, the use of CS-SDAEM NPs (independently of the polyester type) was the most promising formulation approach.

Super absorbent chitosan-based hydrogel sponges as carriers for caspofungin antifungal drug.

Novel chitosan copolymers (CS-g-SBMA) grafted with [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA) in various molar ratio 1.5:1, 5:1, 11.5:1 and 20:1, were synthesized in the present study. SBMA was selected as zwitterion molecule showing promising antibacterial properties. Grafted chitosan derivatives were fully characterized for their successful synthesis by NMR and FT-IR, for their crystallinity by XRD showing reduced crystallinity compared to CS alone. Furthermore, swelling studies were conducted with the grafted derivatives showing extensive swelling capacity (maximum degree of swelling up to 1800%) and water absorption was studied with differential scanning calorimetry and equilibrium water adsorption/desorption isotherms were analyzed. Caspofungin, a novel antifungal drug, was used to prepare a double-acting system, with both antibacterial and antifungal properties, proper for topical use. Drug loaded hydrogels were prepared with 10, 20 and 30 wt% drug content and the loaded hydrogels were fully characterized while antimicrobial studies showed enhanced properties. Caspofungin in vitro release showed an initial burst effect followed by a diffusion process while data analysis verified the initial burst release followed by a quasi Fickian diffusion-driven sustained release. Enhance antimicrobial properties was also observed in caspofungin-loaded hydrogels showing the successful fulfill of our scope; an amphiphilic system having great potential for the development of patches with inherent antimicrobial properties and prolonged antifungal properties.

New Biodegradable Poly(l-lactide)-Block-Poly(propylene adipate) Copolymer Microparticles for Long-Acting Injectables of Naltrexone Drug.

In the present study, novel block copolymers of poly(l-lactide)-block-poly(propylene adipate) (PLLA-b-PPAd) were synthesized in two ratios, 90/10 and 75/25 w/w and were further investigated as long-acting injectable (LAI) polymeric matrices in naltrexone base microparticle formulations. The synthesized polymers were characterized by 1H-NMR, 13C-NMR, FTIR, XRD, TGA and DSC. NMR and FTIR spectroscopies confirmed the successful synthesis of copolymers while DSC showed that these are block copolymers with well-defined and separated blocks. Microparticles were prepared by single emulsification method and were further characterized. Nanoparticles in the range of 0.4-4.5 µm were prepared as indicated by SEM, with copolymers giving the lowest particle size. By XRD and DSC it was found that naltrexone was present in the amorphous state in its microparticles. Dissolution study showed a drug release extending over seven days, indicating that these novel PLLA-b-PPAd copolymers could be promising matrices for naltrexone's LAI formulations. It was evidenced that drug release depended on the copolymer composition. Model release studies showed that drug release is controlled by diffusion.

Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments.

Chitosan (CS) is a hemi-synthetic cationic linear polysaccharide produced by the deacetylation of chitin. CS is non-toxic, highly biocompatible, and biodegradable, and it has a low immunogenicity. Additionally, CS has inherent antibacterial properties and a mucoadhesive character and can disrupt epithelial tight junctions, thus acting as a permeability enhancer. As such, CS and its derivatives are well-suited for the challenging field of ocular drug delivery. In the present review article, we will discuss the properties of CS that contribute to its successful application in ocular delivery before reviewing the latest advances in the use of CS for the development of novel ophthalmic delivery systems. Colloidal nanocarriers (nanoparticles, micelles, liposomes) will be presented, followed by CS gels and lenses and ocular inserts. Finally, instances of CS coatings, aiming at conferring mucoadhesiveness to other matrixes, will be presented.

Dissolution Enhancement and Controlled Release of Paclitaxel Drug via a Hybrid Nanocarrier Based on mPEG-PCL Amphiphilic Copolymer and Fe-BTC Porous Metal-Organic Framework.

In the present work, the porous metal-organic framework (MOF) Basolite®F300 (Fe-BTC) was tested as a potential drug-releasing depot to enhance the solubility of the anticancer drug paclitaxel (PTX) and to prepare controlled release formulations after its encapsulation in amphiphilic methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) nanoparticles. Investigation revealed that drug adsorption in Fe-BTC reached approximately 40%, a relatively high level, and also led to an overall drug amorphization as confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The dissolution rate of PTX-loaded MOF was substantially enhanced achieving a complete (100%) release within four days, while the neat drug only reached a 13% maximum rate (3-4 days). This PTX-Fe-BTC nanocomposite was further encapsulated into a mPEG-PCL matrix, a typical aliphatic amphiphilic copolyester synthesized in our lab, whose biocompatibility was validated by in vitro cytotoxicity tests toward human umbilical vein endothelial cells (HUVEC). Encapsulation was performed according to the solid-in-oil-in-water emulsion/solvent evaporation technique, resulting in nanoparticles of about 143 nm, slightly larger of those prepared without the pre-adsorption of PTX on Fe-BTC (138 nm, respectively). Transmission electron microscopy (TEM) imaging revealed that spherical nanoparticles with embedded PTX-loaded Fe-BTC nanoparticles were indeed fabricated, with sizes ranging from 80 to 150 nm. Regions of the composite Fe-BTC-PTX system in the infrared (IR) spectrum are identified as signatures of the drug-MOF interaction. The dissolution profiles of all nanoparticles showed an initial burst release, attributed to the drug amount located at the nanoparticles surface or close to it, followed by a steadily and controlled release. This is corroborated by computational analysis that reveals that PTX attaches effectively to Fe-BTC building blocks, but its relatively large size limits diffusion through crystalline regions of Fe-BTC. The dissolution behaviour can be described through a bimodal diffusivity model. The nanoparticles studied could serve as potential chemotherapeutic candidates for PTX delivery.

Effect of Poly(vinyl alcohol) on Nanoencapsulation of Budesonide in Chitosan Nanoparticles via Ionic Gelation and Its Improved Bioavailability.

Chitosan (CS) is a polymer extensively used in drug delivery formulations mainly due to its biocompatibility and low toxicity. In the present study, chitosan was used for nanoencapsulation of a budesonide (BUD) drug via the well-established ionic gelation technique and a slight modification of it, using also poly(vinyl alcohol) (PVA) as a surfactant. Scanning electron microscopy (SEM) micrographs revealed that spherical nanoparticles were successfully prepared with average sizes range between 363 and 543 nm, as were measured by dynamic light scattering (DLS), while zeta potential verified their positive charged surface. X-ray diffraction (XRD) patterns revealed that BUD was encapsulated in crystalline state in nanoparticles but with a lower degree of crystallinity than the neat drug, which was also proven by differential scanning calorimetry (DSC) and melting peak measurements. This could be attributed to interactions that take place between BUD and CS, which were revealed by FTIR and by an extended computational study. An in vitro release study of budesonide showed a slight enhancement in the BUD dissolution profile, compared to the neat drug. However, drug release was substantially increased by introducing PVA during the nanoencapsulation procedure, which is attributed to the higher amorphization of BUD on these nanoparticles. The release curves were analyzed using a diffusion model that allows estimation of BUD diffusivity in the nanoparticles.

Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs.

The aim of this work was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with 2-acrylamido-2-methyl-1-propanesulfonic acid (AAMPS) and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSP) as appropriate nanocarriers for the simultaneous ocular administration of dexamethasone sodium phosphate (DxP) and chloramphenicol (CHL). The derivatives CS-AAMPS and CS-MEDSP have been synthesized by free-radical polymerization and their structure has been proved by Fourier-Transformed Infrared Spectroscopy (FT-IR) spectroscopy. Both derivatives exhibited low cytotoxicity, enhanced mucoadhesive properties and antimicrobial activity against Staphylococcus aureus (S.aureus) and Escherichia coli (E. coli). Encapsulation was performed via ionic crosslinking gelation using sodium tripolyphosphate (TPP) as the crosslinking agent. Dynamic light scattering measurements (DLS) showed that the prepared nanoparticles had bimodal distribution and sizes ranging from 50-200 nm and 300-800 nm. Drugs were encapsulated in their crystalline (CHL) or amorphous (DexSP) form inside nanoparticles and their release rate was dependent on the used polymer. The CHL dissolution rate was substantially enhanced compared to the neat drug and the release time was extended up to 7 days. The release rate of DexSP was much faster than that of CHL and was prolonged up to 3 days. Drug release modeling unveiled that diffusion is the main release mechanism for both drugs. Both prepared derivatives and their drug-loaded nanoparticles could be used for extended and simultaneous ocular release formulations of DexSP and CHL drugs.

Hierarchical Porous Carbon-PLLA and PLGA Hybrid Nanoparticles for Intranasal Delivery of Galantamine for Alzheimer's Disease Therapy.

In the present study, poly(l-lactic acid) (PLLA) and poly(lactide-co-glycolide) (PLGA) hybrid nanoparticles were developed for intranasal delivery of galantamine, a drug used in severe to moderate cases of Alzheimer's disease. Galantamine (GAL) was adsorbed first in hierarchical porous carbon (HPC). Formulations were characterized by FT-IR, which showed hydrogen bond formation between GAL and HPC. Furthermore, GAL became amorphous after adsorption, as confirmed by XRD and differential scanning calorimetry (DSC) studies. GAL was quantified to be 21.5% w/w by TGA study. Adsorbed GAL was nanoencapsulated in PLLA and PLGA, and prepared nanoparticles were characterized by several techniques. Their sizes varied between 182 and 394 nm, with an exception that was observed in nanoparticles that were prepared by PLLA and adsorbed GAL that was found to be 1302 nm in size. DSC thermographs showed that GAL was present in its crystalline state in nanoparticles before its adsorption to HPC, while it remained in its amorphous phase after its adsorption in the prepared nanoparticles. It was found that the polymers controlled the release of GAL both when it was encapsulated alone and when it was adsorbed on HPC. Lastly, PLGA hybrid nanoparticles were intranasally-administered in healthy, adult, male Wistar rats. Administration led to successful delivery to the hippocampus, the brain area that is primarily and severely harmed in Alzheimer's disease, just a few hours after a single dose.

Preparation and characterization of Alendronate depot microspheres based on novel poly(-ε-caprolactone)/Vitamin E TPGS copolymers.

In the present study, new aledronate (AL) loaded microspheres were prepared with the use of polycaprolactone (PCL)/Vitamin E d-ɑ-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) copolymers. Specifically, PCL-TPGS copolymers, prepared at several PCL to TPGS ratios (namely, 90/10, 80/20, 70/30 and 60/40 w/w) via a ring opening polymerization process, were characterized by intrinsic viscosity, proton nuclear magnetic resonance (1H NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and enzymatic hydrolysis. Results showed that as TPGS content increases the intrinsic viscosity of the copolymer (and hence, the viscosity-average molecular weight) is decreasing, while FTIR analysis showed the formation of hydrogen bonds between the -C[bond, double bond]O of PCL and the -OH of TPGS. Additionally, XRD analysis indicated that the prepared copolymers were semi-crystalline in nature, while enzymatic hydrolysis studies showed that increasing TGPS content led to increasing copolymer hydrolysis. In the following step, AL drug-loaded microspheres were prepared via single emulsification process. Scanning electron microscopy (SEM) revealed the formation of coarse drug-loaded microspheres with particle size close to 5 µm, while XRD analysis showed that the API was amorphously dispersed only in the cases of high TPGS content. Furthermore, FTIR analysis showed that the API did not interact with the copolymer components, while in vitro drug release studies showed that increasing PCL content led to decreasing API release rate. Finally, analysis of the drug release profiles suggested that the API release mechanism was solely governed by the polymer matrix erosion.

Super-hydrophilic and high strength polymeric foam dressings of modified chitosan blends for topical wound delivery of chloramphenicol.

In the present study polymer blends based on chitosan (CS) and its derivatives with trans-aconitic (t-Acon) acid and another with trimellitic (TRM) anhydride, were prepared for topical wound delivery of chloramphenicol (CHL). FT-IR spectroscopy revealed the successful grafting of t-Acon acid or TRM anhydride into CS macromolecules at molar ratios 1:1 and 1:0.5, while powder X-ray diffraction (XRD) analysis showed that the prepared materials were amorphous. Neat chitosan and its grafted derivatives were mixed in different ratios (25/75, 50/50 and 75/25 w/w) in order to prepare suitable blends. Scanning electron microscopy (SEM) showed that the formed blends after freeze-drying had a sponge-like structure, while thermogravimetric analysis (TGA) verified their thermal stability. All blends are miscible in studied compositions and have extensive swelling and much better mechanical properties than neat CS. In a further step, the obtained porous sponges prepared from CS/CS-derivatives 50/50 w/w were loaded with Chloramphenicol (10, 20 and 30 wt%), a broad-spectrum antibiotic, and the prepared dressings were evaluated in terms of FT-IR, XRD, SEM, and in vitro drug dissolution. An initial burst release followed by a quasi-Fickian diffusion driven sustained release phase was observed while the addition of chloramphenicol gives high antimicrobial properties to all dressings.

Paclitaxel Magnetic Core⁻Shell Nanoparticles Based on Poly(lactic acid) Semitelechelic Novel Block Copolymers for Combined Hyperthermia and Chemotherapy Treatment of Cancer.

Magnetic hybrid inorganic/organic nanocarriers are promising alternatives for targeted cancer treatment. The present study evaluates the preparation of manganese ferrite magnetic nanoparticles (MnFe2O4 MNPs) encapsulated within Paclitaxel (PTX) loaded thioether-containing ω-hydroxyacid-co-poly(d,l-lactic acid) (TEHA-co-PDLLA) polymeric nanoparticles, for the combined hyperthermia and chemotherapy treatment of cancer. Initially, TEHA-co-PDLLA semitelechelic block copolymers were synthesized and characterized by 1H-NMR, FTIR, DSC, and XRD. FTIR analysis showed the formation of an ester bond between the two compounds, while DSC and XRD analysis showed that the prepared copolymers were amorphous. MnFe2O4 MNPs of relatively small crystallite size (12 nm) and moderate saturation magnetization (64 emu·g-1) were solvothermally synthesized in the sole presence of octadecylamine (ODA). PTX was amorphously dispersed within the polymeric matrix using emulsification/solvent evaporation method. Scanning electron microscopy along with energy-dispersive X-ray spectroscopy and transmission electron microscopy showed that the MnFe2O4 nanoparticles were effectively encapsulated within the drug-loaded polymeric nanoparticles. Dynamic light scattering measurements showed that the prepared nanoparticles had an average particle size of less than 160 nm with satisfactory yield and encapsulation efficiency. Diphasic PTX in vitro release over 18 days was observed while PTX dissolution rate was mainly controlled by the TEHA content. Finally, hyperthermia measurements and cytotoxicity studies were performed to evaluate the magnetic response, as well as the anticancer activity and the biocompatibility of the prepared nanocarriers.

Risperidone Controlled Release Microspheres Based on Poly(Lactic Acid)-Poly(Propylene Adipate) Novel Polymer Blends Appropriate for Long Acting Injectable Formulations.

The present study evaluates the preparation of risperidone controlled release microspheres as appropriate long-acting injectable formulations based on a series of novel biodegradable and biocompatible poly(lactic acid)⁻poly(propylene adipate) (PLA/PPAd) polymer blends. Initially, PPAd was synthesized using a two-stage melt polycondensation method (esterification and polycondensation) and characterized by 1H-NMR, differential scanning calorimetry (DSC), and powder X-ray diffraction (XRD) analyses. DSC and XRD results for PLA/PPAd blends (prepared by the solvent evaporation method) showed that these are immiscible, while enzymatic hydrolysis studies performed at 37 °C showed increased mass loss for PPAd compared to PLA. Risperidone-polyester microparticles prepared by the oil⁻water emulsification/solvent evaporation method showed smooth spherical surface with particle sizes from 1 to 15 µm. DSC, XRD, and Fourier-transformed infrared (FTIR) analyses showed that the active pharmaceutical ingredient (API) was dispersed in the amorphous phase within the polymer matrices, whereas in vitro drug release studies showed risperidone controlled release rates in all PLA/PPAd blend formulations. Finally, statistical moment analysis showed that polyester hydrolysis had a major impact on API release kinetics, while in PLA/PPAd blends with high PLA content, drug release was mainly controlled by diffusion.

Preparation of New Risperidone Depot Microspheres Based on Novel Biocompatible Poly(Alkylene Adipate) Polyesters as Long-Acting Injectable Formulations.

Risperidone (RIS)-loaded microspheres based on poly(alkylene adipate)s derived from dicarboxylic acids and different aliphatic diols were prepared by the oil in water emulsion and solvent evaporation method. Specifically, 3 polyesters, namely poly(ethylene adipate), poly(propylene adipate), and poly(butylene adipate), were prepared with the aid of a 2-stage melt-polycondensation method and characterized by gel permeation chromatography, proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry, and X-ray diffraction analysis. Results showed that the molecular weight of the polyesters increased as the diol molecular weight increased, while all polymers were of semi-crystalline nature and the melting temperature was varying from 49.1°C to 51.8°C and 65.9°C for poly(propylene adipate), poly(ethylene adipate), and poly(butylene adipate), respectively. The particle size of the RIS-loaded microspheres varied from 10 to 100 µm depending on the polyester type and the drug loading, while X-ray diffraction analysis revealed amorphous active pharmaceutical ingredient in the cases of high drug-loaded microspheres. In vitro drug release studies along with scanning electron microscopy images of microspheres after the completion of dissolution process showed that in all cases RIS release was controlled by the glass transition temperature of polyesters and physical state of active pharmaceutical ingredients via diffusion.

Amphiphilic Block Copolymer Microspheres Derived from Castor Oil, Poly(ε-carpolactone), and Poly(ethylene glycol): Preparation, Characterization and Application in Naltrexone Drug Delivery.

In the present study, the newly synthesized castor oil-derived thioether-containing ω-hydroxyacid (TEHA) block copolymers with polycaprolactone (TEHA-b-PCL), with methoxypoly(ethylene glycol) (mPEG), (TEHA-b-mPEG) and with poly(ethylene glycol) (PEG) (TEHA-b-PEG-b-TEHA), were investigated as polymeric carriers for fabrication of naltrexone (NLX)-loaded microspheres by the single emulsion solvent evaporation technique. These microspheres are appropriate for the long-term treatment of opioid/alcohol dependence. Physical properties of the obtained microspheres were characterized in terms of size, morphology, drug loading capacity, and drug release. A scanning electron microscopy study revealed that the desired NLX-loaded uniform microspheres with a mean particle size of 5⁻10 µm were obtained in all cases. The maximum percentage encapsulation efficiency was found to be about 25.9% for the microspheres obtained from the TEHA-b-PEG-b-TEHA copolymer. Differential scanning calorimetry and X-ray diffractometry analysis confirmed the drug entrapment within microspheres in the amorphous state. In vitro dissolution studies revealed that all NLX-loaded formulations had a similar drug release profile: An initial burst release after 24 h, followed by a sustained and slower drug release for up to 50 days. The analysis of the release kinetic data, which were fitted into the Korsmeyer⁻Peppas release model, indicated that diffusion is the main release mechanism of NLX from TEHA-b-PCL and TEHA-b-mPEG microspheres, while microspheres obtained from TEHA-b-PEG-b-TEHA exhibited a drug release closer to an erosion process.

Melt extrusion process for adjusting drug release of poorly water soluble drug felodipine using different polymer matrices.

The purpose of the present study was to use commercial available polymers like PVP/PEG, soluplus® and kollidon® SR to prepare immediate and sustained release formulations of felodipine by hot melt mixing method. Solid dispersions containing 5, 10, 20 and 30wt% drug have been prepared in a Haake-Buchler Reomixer at melt temperature 130°C and mixing time 10min. As was found from DSC and XDR studies completely amorphous and miscible solid dispersions can be prepared. In all cases a single glass transition was recorded, which is depended from the used drug amount. Hydrogen bonds and the molecular interaction between felodipine and polymer matrices are responsible for the miscibility of prepared formulations. This has as result the substantial enhancement of felodipine release rate in PVP/PEG mixture and due to the high solubility of used polymers immediate release formulations have been prepared. On the contrary, sustained release formulations can be prepared in the case of kollidon SR solid dispersions. The release mechanism of all preparations was studied using different kinetic models. Finally, binding affinity values calculated by molecular docking simulations were used as estimators for predicting long-term drug's physical stability in solid dispersions.