Slow release of ciprofloxacin from double potential drug delivery system

Psyllium polysaccharide is a bulk laxative and has been used for the treatment of constipation which is responsible for the diverticulitis. Ciprofloxacin is an antibiotic used for the microorganism infested in the diverticula. Hence, the functionalization of psyllium with polyvinyl alcohol (PVA) and poly(acrylamide) [poly(AAm)] will develop the drug delivery system (DDS) with potential for dual action for the treatment of diverticulitis, that is, by treating the constipation due to laxative action of psyllium and release of ciprofloxacin from DDS in controlled manner. The optimum conditions for the synthesis of hydrogels have been obtained as 42.21 × 10⁻² mol/L of AAm, 3% (w/v) of PVA, 32.43 × 10⁻³ mol/L of N,N′-methylenebisacrylamide (NN-MBA), 17.53 × 10⁻³ mol/L ammonium persulfate, and 1 g of psyllium. The characterization of the hydrogels has been carried out by SEMs, EDAX, FTIR, and swelling studies. Swelling and drug release studies have also been carried out to determine the mechanism of swelling of hydrogels and drug release from the drug loaded hydrogels. The release of the drug from the hydrogels occurred through Fickian diffusion mechanism in pH 2.2 and pH 7.4 buffer.     

Synthesis and properties

Poly(D,L lactic acid) was prepared by bulk polymerization of D,L lactide, both under atmospheric pressure and in vacuum. The obtained polymeric products were characterized in terms of molecular weight, Mw, melting point, calorimetric response and swelling behaviour. All products were amorphous. Their molecular weights were determined by viscosimetry and ranged from 2×103 to 9×104. Similarly, the melting points ranged from 90 to 210°C. Swelling experiments, with specimens immersed in buffer solutions, showed that hydrolytic degradation started in a few days for the low Mw material, whereas for the higher molecular weight products it took much longer and probably followed a two-stage mechanism. This study suggests that the high molecular weight material could be an interesting carrier for the preparation of controlled release products, in cases where prolonged delivery is necessary. © 1999 Kluwer Academic Publishers     

药物缓释材料聚(乳酸-丙氨酸)的直接法合成与表征

直接以外消旋乳酸(LA)、L-丙氨酸(Ala)为原料[n(LA):n(Ala)=9:1],采用熔融聚合法合成药物缓释材料聚(乳酸-丙氨酸)共聚物[P(LA-co-Ala)],并用特性黏数、FTIR、1H NMR、GPC、DSC、XRD等手段进行系统表征.熔融共聚中采用一次投料并分次预聚,可生成重均相对分子质量(Mw)达3200(分散度Mw/Mn＝1.23)的共聚物,相对分子质量可以达到丙交酯开环共聚法的水平.首次报道了P(LA-co-Ala)]药物缓释材料的DSC与XRD表征结果,其与聚外消旋乳酸(PDLLA)相比,共聚物具有较低的Tg、Tm和结晶度.新方法步骤少、操作简便,且成本更加低廉.     

Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery

Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram‐positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L‐lactide‐co‐glycolide) (PLGA) nano‐formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH‐PLA and CLH‐PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH‐PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies.Inspec keywords: drug delivery systems, biomedical materials, antibacterial activity, nanoparticles, nanomedicine, microorganisms, polymers, nanofabrication, differential scanning calorimetry, encapsulation, drugs, scanning electron microscopy, Fourier transform infrared spectraOther keywords: Streptococcus faecalis, Bacillus cereus, DSC, stable nanoformulation, monodispersed nanoformulation, pathogenic bacteria, FTIR spectra, molecular dispersion, thermal behaviour, controlled release profile, Fourier transform infrared spectra, differential scanning calorimetry, scanning electron microscopy, drug loading, encapsulation efficiency, polymer concentration, solvent evaporation method, molecular level, drug bioavailability, stabilised clindamycin encapsulated poly lactic acid‐poly (D,L‐lactide‐co‐glycolide) nanoformulation, protozoa, Chlamydia, anaerobic bacteria, gram‐positive aerobes, antimicrobial activity, oral antibiotics, oral delivery, PLA‐PLGA based nanoparticle system, clindamycin hydrochloride     

Sunitinib release from biodegradable films of poly(l-lactide-co-caprolactone)

The aim of this study was to prepare sunitinib-loaded biodegradable films using poly(l-lactide-co-?-caprolactone) (PLCL) for anti-tumor drug delivery. Sunitinib-loaded PLCL film has a rough surface, while empty film has a smooth surface. PLCL film loaded with 5% (w/w) sunitinib showed an absence of a crystalline peak of sunitinib, while sharp peaks were observed at 10% (w/w) loading, indicating that sunitinib was molecularly distributed in the polymer matrix at 5% (w/w). A drug release study revealed an initial burst during the first 2 h, followed by continuous release until 24 h. Since weight loss of film was <10% for 1 week, drug release mechanism was dominantly dependent on the diffusion-mediated release of drugs to the medium. Sunitinib has a dose-dependent anti-proliferation effect against HuCC-T1 human cholangiocarcinoma cells in vitro. These results indicate that sunitinib-loaded PLCL film is a appropriate candidate as a vehicle for anti-tumor drug delivery.     

A novel risperidone-loaded SAIB–PLGA mixture matrix depot with a reduced burst release: effects of solvents and PLGA on drug release behaviors in vitro/in vivo

The purpose of this study was to develop an in situ forming SAIB (sucrose acetate isobutyrate)-PLGA (poly (d, lactide-co-glycolide)) mixture matrix depot for sustained release of risperidone. The factors affecting the risperidone release kinetics were investigated to obtain further insight into the drug release mechanisms. The burst release in vitro was significantly reduced (4.95%) by using DMSO as solvent. And, increasing the PLGA content from 2 to 10% w/w decreased the initial release from 6.95 to 1.05%. The initial release in vivo decreased with increasing PLGA content (2.0% w/w PLGA, C _max = 1161.7 ± 550.2 ng ml⁻¹; 10% w/w PLGA, C _max = 280.3 ± 98.5 ng ml⁻¹). The persistence (AUC_4–20 days) over 20 days increased from 76.8 ± 20.7 to 362.8 ± 75.0 ng d ml⁻¹ by inclusion of 10% PLGA compared with the PLGA-free depot. These results demonstrate that the SAIB–PLGA mixture matrix depot could be useful as a sustained delivery system for risperidone.     

可缓释药物的明胶/磷酸钙骨水泥复合组织工程支架材料

采用向孔隙中灌注含聚乳酸聚乙醇酸共聚物（PLGA）载药微球的明胶溶液的方法制备了具有药物缓释功能的明胶/磷酸钙骨水泥复合组织工程支架。用扫描电子显微镜观察了微球和支架的形貌特征,用万能材料试验机测定了支架材料的抗压强度,用紫外-可见分光光度计分析了复合支架的释药率。结果表明,灌注明胶对多孔磷酸钙骨水泥支架起到显著的增强作用,抗压强度达2.42 MPa。复合支架携载硫酸庆大霉素, 具有良好的药物缓释功能,缓释时间可达30天以上,使支架在修复骨缺损的同时能消除炎症反应,成为一种集骨修复和治疗于一体的新型组织工程支架材料,具有良好的应用前景。      

New synthesis method of HA/P(D,L)LA composites: study of fibronectin adsorption and their effects in osteoblastic behavior for bone tissue engineering

A novel synthetic method to synthesize hydroxyapatite/poly (D,L) lactic acid biocomposite is presented in this study by mixing only the precursors hydroxyapatite and (D,L) LA monomer without adding neither solvent nor catalyst. Three compositions were successfully synthesized with the weight ratios of 1/1, 1/3, and 3/5 (hydroxyapatite/(D,L) lactic acid), and the grafting efficiency of poly (D,L) lactic acid on hydroxyapatite surface reaches up to 84?%. Scanning electron microscopy and Fourier transform infrared spectroscopy showed that the hydroxyapatite particles were successfully incorporated into the poly (D,L) lactic acid polymer and X ray diffraction analysis showed that hydroxyapatite preserved its crystallinity after poly (D,L) lactic acid grafting. Differential scanning calorimetry shows that Tg of hydroxyapatite/poly (D,L) lactic acid composite is less than Tg of pure poly (D,L) lactic acid, which facilitates the shaping of the composite obtained. The addition of poly (D,L) lactic acid improves the adsorption properties of hydroxyapatite for fibronectin extracellular matrix protein. Furthermore, the presence of poly (D,L) lactic acid on hydroxyapatite surface coated with fibronectin enhanced pre-osteoblast STRO-1 adhesion and cell spreading. These results show the promising potential of hydroxyapatite/poly (D,L) lactic acid composite as a bone substitute material for orthopedic applications and bone tissue engineering.     

One‐step method for the preparation of poly(methyl methacrylate) modified titanium‐bioactive glass three‐dimensional scaffolds for bone tissue engineering

A novel three‐dimensional (3D) titanium (Ti)‐doping meso‐macroporous bioactive glasses (BGs)/poly(methyl methacrylate) (PMMA) composite was synthesised using PMMA and EO₂₀ PO₇₀ EO₂₀ (P₁₂₃) as the macroporous and mesoporous templates, respectively. Unlike the usual calcination method, the acid steam technique was used to improve the polycondensation of Ti‐BGs, and then PMMA was partially extracted via chloroform to induce the macroporous structure. Simultaneously, the residual PMMA which remained in the wall enhanced the compressive strength to 2.4 MPa (0.3 MPa for pure BGs). It is a simple and green method to prepare the macro‐mesoporous Ti‐BGs/PMMA. The materials showed the 3D interconnected hierarchical structure (250 and 3.4 nm), making the fast inducing‐hydroxyapatite growth and the controlled drug release. Besides mentioned above, the good antimicrobial property and biocompatible of the scaffold also ensure it is further of clinical use. Herein, the fabricated materials are expected to have potential application on bone tissue regeneration.Inspec keywords: titanium, bone, tissue engineering, glass, materials preparation, biomedical materials, polymers, porous materials, drug delivery systems, nanomedicineOther keywords: poly(methyl methacrylate), PMMA preparation, 3D titanium‐bioactive glass scaffold, bone tissue engineering, titanium‐doping mesomacroporous bioactive glass, bioactive glass‐PMMA composite, macroporous template, mesoporous template, calcination method, acid steam technique, titanium‐bioactive glass polycondensation, macroporous structure, green method, macromesoporous titanium‐bioactive glass‐PMMA, 3D interconnected hierarchical structure, fast inducing‐hydroxyapatite growth, controlled drug release, bone tissue regeneration, Ti     

Comparison of two polymeric carrier formulations for controlled release of hydrophilic and hydrophobic drugs

Two temperature sensitive drug carriers, poly (N-isopropylacrylamide-co-acrylic acid) (PNIPA-co-AA) and poly (N-isopropylacrylamide-vinyl pyrrolidone-acrylic acid) (PNIPA-VP-AA), were successfully synthesized through free radical mechanism. The diameters of PNIPA-co-AA and PNIPA-VP-AA particles can be regulated to be less than 100 nm, which were related to surfactant sodiumdodecyl sulfate and initiator ferrous ammonium sulfate, respectively. The lower critical solution temperature (LCST) of them can be manipulated to be higher than 40 °C, which was correlated to amount of acrylic acid (AA) that was copolymerized with NIPA. Hydrophilic anti-tumor drugs, 5-fluorouracil (5-Fu) and hydrophobic drug thalidomide were entrapped into PNIPA-co-AA and PNIPA-VP-AA, respectively. For different interaction mechanism between drug and carrier, 5-Fu was prone to be entrapped in PNIPA-co-AA with loading efficiency larger than 10% (w/w), while thalidomide was entrapped in PNIPA-VP-AA up to 80% (w/w). Fluorescein, an angiography agent, was used to evaluate the drug loading mechanism between PNIPA-VP-AA and poor water-soluble drug. In vitro drug release behavior from these two drug carriers were significantly different and showed temperature dependent, which demonstrated that PNIPA-co-AA and PNIPA-VP-AA are promising candidates for different controlled drug delivery system.     

Fabrication of poly(D,L‐lactic acid) nanoparticles as delivery system for sustained release of L‐theanine

L‐theanine is present in tea as a unique, free, non‐protein amino acid. Due to various beneficial effects on brain activity, it is widely used as a nutraceutical. After consumption, it is rapidly absorbed and metabolised followed by excretion through urine. Therefore, the authors developed an L‐theanine delivery system by encapsulating into polymeric nanoparticles to release it slowly and make it available for a longer period of time. Poly(D, L‐lactic acid) nanoparticle (PLANP) was fabricated by the double emulsion method and L‐theanine was encapsulated into it (PLANP‐T). Spherical nanoparticles with a hydrodynamic diameter of 247 and 278 nm and surface charge of −14.5 and −25.7 mV for PLANP and PLANP‐T, respectively, were fabricated. The Fourier transform infrared spectroscopic data indicated encapsulation of L‐theanine into PLANP. The PLANP showed high L‐theanine encapsulation capacity (71.65%) with a sustained release character. The maximum release (66.3%) of L‐theanine was recorded in pH 7.3 at 48 h. The release kinetics followed the Higuchi model and the release mechanism was determined as super case‐II transport (erosion). This slow release will make it available to the target tissue for a longer period of time (sustain release effect) and will also avoid immediate metabolism and clearance from the circulation.Inspec keywords: nanomedicine, pH, polymers, nanofabrication, emulsions, biomedical materials, drug delivery systems, nanoparticles, Fourier transform infrared spectraOther keywords: brain activity, L‐theanine delivery system, polymeric nanoparticles, double emulsion method, spherical nanoparticles, surface charge, L‐theanine encapsulation capacity, poly(D, L‐lactic acid) nanoparticles, nonprotein amino acid, urine, hydrodynamic diameter, Fourier transform infrared spectroscopy, time 48.0 hour, voltage ‐25.7 mV, voltage ‐14.5 mV, size 278.0 nm, size 247.0 nm, target tissue, Higuchi model, pH     

Inhibition of 3‐D Tumor Spheroids by Timed‐Released Hydrophilic and Hydrophobic Drugs from Multilayered Polymeric Microparticles

First‐line cancer chemotherapy necessitates high parenteral dosage and repeated dosing of a combination of drugs over a prolonged period. Current commercially available chemotherapeutic agents, such as Doxil and Taxol, are only capable of delivering single drug in a bolus dose. The aim of this study is to develop dual‐drug‐loaded, multilayered microparticles and to investigate their antitumor efficacy compared with single‐drug‐loaded particles. Results show hydrophilic doxorubicin HCl (DOX) and hydrophobic paclitaxel (PTX) localized in the poly(dl ‐lactic‐co‐glycolic acid, 50:50) (PLGA) shell and in the poly(l ‐lactic acid) (PLLA) core, respectively. The introduction of poly[(1,6‐bis‐carboxyphenoxy) hexane] (PCPH) into PLGA/PLLA microparticles causes PTX to be localized in the PLLA and PCPH mid‐layers, whereas DOX is found in both the PLGA shell and core. PLGA/PLLA/PCPH microparticles with denser shells allow better control of DOX release. A delayed release of PTX is observed with the addition of PCPH. Three‐dimensional MCF‐7 spheroid studies demonstrate that controlled co‐delivery of DOX and PTX from multilayered microparticles produces a greater reduction in spheroid growth rate compared with single‐drug‐loaded particles. This study provides mechanistic insights into how distinctive structure of multilayered microparticles can be designed to modulate the release profiles of anticancer drugs, and how co‐delivery can potentially provide better antitumor response.     

Innovation of novel ‘Tab in Tab’ system for release modulation of milnacipran HCl: optimization,formulation and in vitro investigations

The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel^®) and hydrophobic (Compritol^®) polymers. 3² full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel^® and 8.21% w/w of Compritol^® exhibited drug release pattern close proximal to the ideal theoretical profile (t_50% = 5.92?h, t_75% = 11.9?h, t_90% = 18.11 h). The phenomenon of drug release was further explained by concept of percolation and the role of Benecel^® and Compritol^® in drug release retardation was studied. The normalized error obtained from ANN was less, compared with the multiple regression analysis, and exhibits the higher accuracy in prediction. The results of short-term stability study revealed stable chataracteristics of TITs. SEM study of TITs at different dissolution time points confirmed both diffusion and erosion mechanisms to be operative during drug release from the batch A10. Novel TITs can be a succesful once a day delivery system for highly water soluble drugs.     

In vitro study of drug-eluting stent coatings based on poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) incorporating cyclosporine A – drug release,polymer degradation and mechanical integrity

In this study, absorbable polymer stent coatings for localized drug delivery based on poly(l-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and β-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced polymer degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26–33%) was found for CsA concentrations of 4 × 10⁻⁵ to 4 × 10⁻⁷ mol/l. Marked molecular weight reduction (70–80%) of the PLLA matrix occurred after β-sterilization. We also observed a substantial decrease of in vitro degradation time. The maintenance of the mechanical integrity of the polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8–0.9 N was measured.     

New PMMA-based composites for preparing spacer devices in prosthetic infections

Even though the systemic antibiotic therapy is usually applied after prosthetic infections surgical treatments, it is unable to reach the infection site in sufficient concentrations to eradicate bacteria. Delivering antibiotics locally with the use of custom made device (spacer or nail coating) might eradicate or reduce the infection and the risk of recolonization, providing a very high concentration of antibiotic. PMMA-based (Mendec Spine^®) composites with BaSO₄ were enriched with β-tricalcium phosphate (Porosectan-TCP) or only a slightly higher BaSO₄ concentration (Porosectan-BaSO₄) to obtain higher porosity. The aim of the study was to evaluate: (i) drug absorption capability and drug release kinetics in vitro soaking them with a combined solution of gentamicin and vancomycin, (ii) their in vitro and in vivo biocompatibility, and finally, (iii) they were tested preliminarily in an experimental model of bone infection. The simultaneous presence of β-TCP and BaSO₄ resulted in the formation of a texture of interconnecting channels with different diameters, from a few microns to several hundred microns, which totally filled the material. The porosity, determined by microcomputed tomography, was significantly higher in both tested plain composites (Porosectan-TCP: +17.3%; Porosectan-BaSO₄: +7.5%) in comparison to control composite material (Mendec Spine^®). The kinetics of antibiotic release from composites was rapid and complete, producing high drug concentrations for a short period of time. Both composites showed a good level of biocompatibility. The osteomyelitic model confirmed that both composites, soaked in antibiotic solution, were able to cure bone infection. These composites could be useful for preparing devices for prosthetic joint infections treatment also allowing the use of antibiotics solution at required concentrations.     

Mesoporous bioactive glass as a drug delivery system: fabrication, bactericidal properties and biocompatibility

Implant-associated infection remains a difficult medical problem in orthopaedic surgery. Here, we report on the fabrication of gentamicin-loaded mesoporous bioactive glass (Gent-MBG) for use as a controlled antibiotic delivery system to achieve the sustained release of antibiotics in the local sites of bone defects. The high surface area and mesoporous structure of MBG enable higher drug loading efficiency (79–83 %) than non-mesoporous biological glass (NBG) (18–19 %). Gent-MBG exhibits sustained drug release for more than 6 days, and this controlled release of gentamicin significantly inhibits bacterial adhesion and prevents biofilm formation by S. aureus (ATCC25923) and S. epidermidis (ATCC35984). Biocompatibility tests with human bone marrow stromal cells (hBMSCs) indicate that MBG has better biocompatibility than NBG. Therefore, Gent-MBG can be used as a controlled drug delivery system to prevent and/or treat orthopedic peri-implant infections.     

聚乳酸/杆菌肽静电纺丝纤维的体外释药研究

为探讨聚乳酸纤维结构形貌对杆菌肽药物的缓慢释放行为及作用机理,通过静电纺丝法制备了聚乳酸/杆菌肽单轴纤维、聚乳酸/杆菌肽串珠和(聚乳酸/杆菌肽)-聚乳酸同轴核-壳纤维等聚乳酸/杆菌肽药物缓释体系,并采用红外光谱法和差热分析法对其化学结构和热性能进行了表征.利用紫外分光光度计法研究了不同载药体系的体外药物释放行为,并探索了不同降解时期载药纤维的质量和形貌变化规律.研究表明:杆菌肽与聚乳酸主要为物理结合;聚乳酸单轴纤维和串珠对杆菌肽的扩散释放机理,属于纯Fick扩散;采用单轴和同轴静电纺丝技术可以获得两种不同释药特性的载药纤维.单轴纤维和串珠能够将药物快速释放,适合抗生素的治疗;同轴纤维中药物受控释放,更适合长期、小剂量的药物释放.     

氨基酸改性聚乳酸共聚物的合成及降解研究进展

为了改善聚乳酸的降解速率,提高其与细胞的亲和性,氨基酸对聚乳酸的改性研究引起了人们的关注。综述了聚(乳酸-氨基酸)共聚物的各种合成路线及产物降解性能的研究进展。在聚乳酸(PLA)分子中引入氨基酸,可以使产物的大分子侧链获得氨基、羟基、羧基等活性基团。与PLA相比,此类聚合物的降解性能有所提高,具有两亲性和良好的细胞相容性,可用于药物缓释体系及组织工程。     

Quaternized chitosan (QCS) nanoparticles as a novel delivery system for ammonium glycyrrhizinate

The aim of this study was to generate a new type of nanoparticles made of quaternized chitosan (QCS) and poly(aspartic acid) via the ionotropic gelation technique and to evaluate their potential for the association and delivery of ammonium glycyrrhizinate (GLA). The effects of the pH value of nanoparticles, QCS molecular weight (Mw) and poly(aspartic acid) concentration on GLA encapsulation were studied. Suitably pH value of nanoparticles, moderate QCS MW, optimal concentration ratio of poly(aspartic acid) and QCS favored higher GLA encapsulation efficiency. The release of GLA from nanoparticles was pH-dependent. Fast release occurred in 0.1 M phosphate buffer solution (PBS, pH = 7.4), while the release was slow in 0.1 M HCl (pH = 1.2). The results showed that the new QCS/poly(aspartic acid) nanoparticles have a promising potential in GLA delivery system.     

Synthesis and characterization of amphiphilic star-shaped copolymers based on β-cyclodextrin for micelles drug delivery

Purpose: A series of β-CD amphiphilic star-shaped copolymers with exceptional characteristics were synthesized and their potential as carriers for micelles drug delivery was investigated.

Methods: A series of amphiphilic copolymers based on β-CD were synthesized by introducing poly (acrylic acid)-co-poly(methyl methacrylate)-poly (vinyl pyrrolidone) or poly (acrylic acid)-co-poly(methyl methacrylate)-co-poly(monoacylated-β-CD)-poly (vinyl pyrrolidone) blocks to the primary hydroxyl group positions of β-CD. The micellization behavior of the copolymers, the synthesis conditions, characteristics, drug release in vitro and tissue distribution of vinpocetine (VP) micelles in vivo were investigated.

Results: Around 60 types of β-CD amphiphilic star-shaped copolymers were successfully synthesized and the critical micelle concentration ranged from 9.80?×?10^?4 to 5.24?×?10^?2g/L. The particle size, drug loading and entrapment efficiency of VP-loaded β-CD-P₄ micelles prepared with optimal formulation were about 65?nm, 21.44?±?0.14%, and 49.05?±?0.36%, respectively. The particles had good sphericity. The cumulative release rates at 72?h of VP-loaded β-CD-P₄ micelles in pH 1.0, pH 4.5, pH 6.5, or pH 7.4 media were 93%, 69%, 49%, and 43%, respectively. And, the lung targeting efficiency of VP-loaded β-CD-P₄ micelles was 8.98 times higher than that of VP injection.

Conclusion: The VP-loaded β-CD-P₄ micelles exhibited controlled-release property, pH-induced feature and lung targeting capacity compared with VP injection, suggesting that the β-CD-P₄ copolymers are an excellent candidate for micelles drug delivery.