Fabrication of a Reservoir Ring for Sustained and Prolonged Release of Levonorgestrel for Vaginal Administration

Introduction: More than one-third of women experience abnormal uterine bleeding (AUB) during their lifetime. One of the treatment methods of this disease is hormone therapy. Vaginal rings (VRs) containing progesterone hormones could be a good choice for treatment. In this study, the design and construction of a reservoir ring with the ability to release levonorgestrel hormone has been investigated. Methods: In this experimental study, to make vaginal rings containing levonorgestrel, biocompatible silicone fibers were used, the two ends of which were connected with special caps. Different amounts of LNG including 0.1, 0.2 and 0.4 weight percent relative to paraffin were loaded into the fibers. These three prototypes were named RSC1, RSC2, and RSC3, respectively. The daily and cumulative release of LNG from these rings was measured by spectrophotometer and compared using SPSS software version 16 and analyzed by one-way ANOVA method. Results: On the first day, there was a burst release that was different for these three prototypes depending on the drug loading percentage. From the second until thirtieth day for RSC3 and from forth until thirtieth day for RSC1 and RSC2, prolonged release was achieved and average daily release for RSC1, RSC2, and RSC3 were 24.10 ± 8.22, 41.77 ± 9.02 and 83.29 ± 5.07µg, respectively. Conclusion: According to the findings, it is possible to design VRs capable of prolonged and sustained release of LNG for up to 30 days and control their daily release rate based on initial drug loading. This method may be a suitable alternative to oral hormonal pills in the treatment of AUB.

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Adsorption and Sustained Delivery of Small Molecules from Nanosilicate Hydrogel Composites

Pharmaceuticals ◽

10.3390/ph15010056 ◽

2022 ◽

Vol 15 (1) ◽

pp. 56

Author(s):

Samuel Stealey ◽

Mariam Khachani ◽

Silviya Petrova Zustiak

Keyword(s):

Small Molecules ◽

High Surface ◽

High Surface Area ◽

Control Release ◽

Mesh Size ◽

Burst Release ◽

Prolonged Release ◽

Nanocomposite Hydrogels ◽

Small Molecule Therapeutics ◽

And Control

Two-dimensional nanosilicate particles (NS) have shown promise for the prolonged release of small-molecule therapeutics while minimizing burst release. When incorporated in a hydrogel, the high surface area and charge of NS enable electrostatic adsorption and/or intercalation of therapeutics, providing a lever to localize and control release. However, little is known about the physio-chemical interplay between the hydrogel, NS, and encapsulated small molecules. Here, we fabricated polyethylene glycol (PEG)-NS hydrogels for the release of model small molecules such as acridine orange (AO). We then elucidated the effect of NS concentration, NS/AO incubation time, and the ability of NS to freely associate with AO on hydrogel properties and AO release profiles. Overall, NS incorporation increased the hydrogel stiffness and decreased swelling and mesh size. When individual NS particles were embedded within the hydrogel, a 70-fold decrease in AO release was observed compared to PEG-only hydrogels, due to adsorption of AO onto NS surfaces. When NS was pre-incubated and complexed with AO prior to hydrogel encapsulation, a >9000-fold decrease in AO release was observed due to intercalation of AO between NS layers. Similar results were observed for other small molecules. Our results show the potential for use of these nanocomposite hydrogels for the tunable, long-term release of small molecules.

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Composite Polylactic-Methacrylic Acid Copolymer Nanoparticles for the Delivery of Methotrexate

Journal of Drug Delivery ◽

10.1155/2012/579629 ◽

2012 ◽

Vol 2012 ◽

pp. 1-18 ◽

Cited By ~ 13

Author(s):

Bongani Sibeko ◽

Yahya E. Choonara ◽

Lisa C. du Toit ◽

Girish Modi ◽

Dinesh Naidoo ◽

...

Keyword(s):

Methacrylic Acid ◽

Release Kinetics ◽

Drug Loading ◽

Double Emulsion ◽

Central Nervous System Lymphoma ◽

Poly Lactic Acid ◽

Burst Release ◽

Prolonged Release ◽

Strategy Analysis ◽

Sem Images

The purpose of this study was to develop poly(lactic acid)-methacrylic acid copolymeric nanoparticles with the potential to serve as nanocarrier systems for methotrexate (MTX) used in the chemotherapy of primary central nervous system lymphoma (PCNSL). Nanoparticles were prepared by a double emulsion solvent evaporation technique employing a 3-Factor Box-Behnken experimental design strategy. Analysis of particle size, absolute zeta potential, polydispersity (Pdl), morphology, drug-loading capacity (DLC), structural transitions through FTIR spectroscopy, and drug release kinetics was undertaken. Molecular modelling elucidated the mechanisms of the experimental findings. Nanoparticles with particle sizes ranging from 211.0 to 378.3 nm and a recovery range of 36.8–86.2 mg (Pdl≤0.5) were synthesized. DLC values were initially low (12±0.5%) but were finally optimized to 98±0.3%. FTIR studies elucidated the comixing of MTX within the nanoparticles. An initial burst release (50% of MTX released in 24 hours) was obtained which was followed by a prolonged release phase of MTX over 84 hours. SEM images revealed near-spherical nanoparticles, while TEM micrographs revealed the presence of MTX within the nanoparticles. Stable nanoparticles were formed as corroborated by the chemometric modelling studies undertaken.

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Preparation and In Vitro Evaluation of Resealed Erythrocytes as A New Trend in Treatment of Asthma

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v6i3.8889 ◽

2016 ◽

Vol 6 (3) ◽

Author(s):

Mohammed Ibrahim ◽

Alaa Zaky ◽

Mohsen Afouna ◽

Ahmed Samy

Keyword(s):

In Vitro Release ◽

Human Erythrocytes ◽

The Body ◽

Blood Levels ◽

Time Interval ◽

Burst Release ◽

Prolonged Release ◽

Nocturnal Asthma ◽

Carrier Erythrocytes

Carrier erythrocytes are emerging as one of the most promising biological drug delivery systems investigated in recent decades. Beside its biocompatibility, biodegradability and ability to circulate throughout the body, it has the ability to perform extended release system of the drug for a long period. The ultimate goal of this study is to introduce a new carrier system for Salbutamol, maintaining suitable blood levels for a long time, as atrial to resolve the problems of nocturnal asthma medication Therefore in this work we study the effect of time, temperature as well as concentration on the loading of salbutamol in human erythrocytes to be used as systemic sustained release delivery system for this drug. After the loading process is performed the carrier erythrocytes were physically and cellulary characterized. Also, the in vitro release of salbutamol from carrier erythrocytes was studied over time interval. From the results it was found that, human erythrocytes have been successfully loaded with salbutamol using endocytosis method either at 25 Co or at 37 Co . The highest loaded amount was 3.5 mg/ml and 6.5 mg/ml respectively. Moreover, the percent of cells recovery is 90.7± 1.64%. Hematological parameters and osmotic fragility behavior of salbutamol loaded erythrocytes were similar that of native erythrocytes. Scanning electron microscopy demonstrated that the salbutamol loaded cells has moderate change in the morphology. Salbutamol releasing from carrier cell was 43% after 36 hours in phosphate buffer saline. The releasing pattern of the drug from loaded erythrocytes showed initial burst release in the first hour followed by a very slow release, obeying zero order kinetics. It concluded that salbutamol is successfully entrapped into erythrocytes with acceptable loading parameters and moderate morphological changes, this suggesting that erythrocytes can be used as prolonged release carrier for salbutamol.

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The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles

Pharmaceutics ◽

10.3390/pharmaceutics12050455 ◽

2020 ◽

Vol 12 (5) ◽

pp. 455

Author(s):

Emilia Szymańska ◽

Katarzyna Woś-Latosi ◽

Julia Jacyna ◽

Magdalena Dąbrowska ◽

Joanna Potaś ◽

...

Keyword(s):

Drug Release ◽

Polymer Matrix ◽

Drug Loading ◽

Water Soluble ◽

Dissolution Behavior ◽

Complex Nature ◽

Prolonged Release ◽

Scanning Calorimetry ◽

Burst Effect ◽

The Impact

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

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Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading

Molecules ◽

10.3390/molecules26010111 ◽

2020 ◽

Vol 26 (1) ◽

pp. 111

Author(s):

Gordana Stanojević ◽

Djordje Medarević ◽

Ivana Adamov ◽

Nikola Pešić ◽

Jovana Kovačević ◽

...

Keyword(s):

Ethylene Glycol ◽

Release Rate ◽

Drug Loading ◽

Prolonged Release ◽

Cylindrical Shape ◽

Poly Ethylene Glycol ◽

Scanning Calorimetry ◽

3D Printed ◽

Artificial Neural ◽

Poly Ethylene

Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers.

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Targeted Delivery of Amantadine-loaded Methacrylate Nanosphere-ligands for the Potential Treatment of Amyotrophic Lateral Sclerosis

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps29595 ◽

2018 ◽

Vol 21 ◽

pp. 94-109 ◽

Cited By ~ 1

Author(s):

Zamanzima Mazibuko ◽

Sunaina Indermun ◽

Mershen Govender ◽

Pradeep Kumar ◽

Lisa C Du Toit ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Zeta Potential ◽

Targeted Delivery ◽

Ex Vivo ◽

Release Kinetics ◽

Burst Release ◽

Prolonged Release ◽

Chelating Ligand ◽

Study Results ◽

Lateral Sclerosis

Purpose. This study aimed to develop and analyse poly(DL-lactic acid)-methacrylic acid nanospheres bound to the chelating ligand diethylenetriaminepentaacetic acid (DTPA) for the targeted delivery of amantadine in Amyotrophic Lateral Sclerosis (ALS). Methods. The nanospheres were prepared by a double emulsion solvent evaporation technique statistically optimized employing a 3-Factor Box-Behnken experimental design. Analysis of the particle size, zeta potential, polydispersity (Pdl), morphology, drug entrapment and drug release kinetics were carried out. Results. The prepared nanospheres were determined to have particle sizes ranging from 68.31 to 113.6 nm (Pdl ≤ 0.5). An initial burst release (50% of amantadine released in 24 hr) was also obtained, followed by a prolonged release phase of amantadine over 72 hr. Successful conjugation of the chelating ligand onto the surface of the optimised nanospheres was thereafter achieved and confirmed by TEM. The synthesized modified nanospheres were spherical in shape, 105.6 nm in size, with a PdI of 0.24 and zeta potential of -28.0 mV. Conjugation efficiency was determined to be 74%. In vitro and ex vivo cell study results confirmed the intracellular uptake of the modified nanospheres by the NSC-34 cell line and the non-cytotoxicity of the synthesized nanospheres. Conclusions. Biocompatible amantadine-loaded nanospheres were successfully designed, characterized and optimized employing the randomized Box-Behnken statistical design. Delivery of amantadine over 72 hrs was achieved, with the nanospheres being of a size capable of internalization by the NSC- 34 cells. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Collagen Scaffolds Containing Hydroxyapatite-CaO Fiber Fragments for Bone Tissue Engineering

Polymers ◽

10.3390/polym12051174 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1174 ◽

Cited By ~ 1

Author(s):

Shiao-Wen Tsai ◽

Sheng-Siang Huang ◽

Wen-Xin Yu ◽

Yu-Wei Hsu ◽

Fu-Yin Hsu

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Drug Loading ◽

Sol Gel ◽

Regeneration Ability ◽

Burst Release ◽

Electrospinning Technique

Collagen (COL) and hydroxyapatite (HAp) are the major components of bone, therefore, COL-HAp composites have been widely used as bone substitutes to promote bone regeneration. We have reported that HAp-CaO fibers (HANFs), which were fabricated by a sol-gel route followed by an electrospinning technique, possessed good drug-loading efficiency and limited the burst release of tetracycline. In the present study, we used HANF fragments to evaluate the effects of COL-HANF scaffolds on MG63 osteoblast-like cell behaviors. COL-HANF composite scaffolds in which the average diameter of HANFs was approximately 461 ± 186 nm were fabricated by a freeze-drying process. The alkaline phosphatase activity and the protein expression levels of OCN and BSP showed that compared with COL alone, the COL-HANF scaffold promoted the differentiation of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the COL-HANF scaffold was examined by using a rabbit condylar defect model in vivo. The COL-HANF scaffold was biodegradable and promoted bone regeneration eight weeks after the operation. Hence, we concluded that the COL-HANF scaffold has potential as a bone graft for bone tissue engineering.

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Thymoquinone-Loaded Soluplus®-Solutol® HS15 Mixed Micelles: Preparation, In Vitro Characterization, and Effect on the SH-SY5Y Cell Migration

Molecules ◽

10.3390/molecules25204707 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4707

Author(s):

Maria Camilla Bergonzi ◽

Marzia Vasarri ◽

Giulia Marroncini ◽

Emanuela Barletta ◽

Donatella Degl’Innocenti

Keyword(s):

Cell Migration ◽

Load Capacity ◽

Drug Loading ◽

Neuroblastoma Cell ◽

In Vitro Release ◽

Human Neuroblastoma Cell ◽

Prolonged Release ◽

Human Neuroblastoma ◽

Vitro Release

Thymoquinone (TQ) is the main active ingredient of Nigella sativa essential oil, with remarkable anti-neoplastic activities with anti-invasive and anti-migratory abilities on a variety of cancer cell lines. However, its poor water solubility, high instability in aqueous solution and pharmacokinetic drawbacks limits its use in therapy. Soluplus® and Solutol® HS15 were employed as amphiphilic polymers for developing polymeric micelles (SSM). Chemical and physical characterization studies of micelles are reported, in terms of size, homogeneity, zeta potential, critical micelle concentration (CMC), cloud point, encapsulation efficiency (EE%), load capacity (DL), in vitro release, and stability. This study reports for the first time the anti-migratory activity of TQ and TQ loaded in SSM (TQ-SSM) in the SH-SY5Y human neuroblastoma cell line. The inhibitory effect was assessed by the wound-healing assay and compared with that of the unformulated TQ. The optimal TQ-SSM were provided with small size (56.71 ± 1.41 nm) and spherical shape at ratio of 1:4 (Soluplus:Solutol HS15), thus increasing the solubility of about 10-fold in water. The entrapment efficiency and drug loading were 92.4 ± 1.6% and 4.68 ± 0.12, respectively, and the colloidal dispersion are stable during storage for a period of 40 days. The TQ-SSM were also lyophilized to obtain a more workable product and with increased stability. In vitro release study indicated a prolonged release of TQ. In conclusion, the formulation of TQ into SSM allows a bio-enhancement of TQ anti-migration activity, suggesting that TQ-SSM is a better candidate than unformulated TQ to inhibit human SH-SY5Y neuroblastoma cell migration.

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Biological Properties of Ti-Nb-Zr-O Nanostructures Grown on Ti35Nb5Zr Alloy

Journal of Nanomaterials ◽

10.1155/2012/834042 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Zhaohui Li ◽

Congqin Ning ◽

Dongyan Ding ◽

Hegang Liu ◽

Lin Huang

Keyword(s):

Stem Cell ◽

Drug Release ◽

Drug Loading ◽

Biological Properties ◽

Prolonged Release ◽

Apatite Formation ◽

Release Process ◽

Oxide Nanostructures ◽

Implant Alloys

Surface modification of low modulus implant alloys with oxide nanostructures is one of the important ways to achieve favorable biological behaviors. In the present work, amorphous Ti-Nb-Zr-O nanostructures were grown on a peak-aged Ti35Nb5Zr alloy through anodization. Biological properties of the Ti-Nb-Zr-O nanostructures were investigated throughin vitrobioactivity testings, stem cell interactions, and drug release experiments. The Ti-Nb-Zr-O nanostructures demonstrated a good capability of inducing apatite formation after immersion in simulated body fluids (SBFs). Drug delivery experiment based on gentamicin and the Ti-Nb-Zr-O nanostructures indicated that a high drug loading content could result in a prolonged release process and a higher quantity of drug residues in the oxide nanostructures after drug release. Quick stem cell adhesion and spreading, as well as fast formation of extracellular matrix materials on the surfaces of the Ti-Nb-Zr-O nanostructures, were found. These findings make it possible to further explore the biomedical applications of the Ti-Nb-Zr-O nanostructure modified alloys especially clinical operation of orthopaedics by utilizing the nanostructures-based drug-release system.

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Thermosensitive Chitosan Hydrogels Containing Polymeric Microspheres for Vaginal Drug Delivery

BioMed Research International ◽

10.1155/2017/3564060 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 7

Author(s):

Ting-Ting Yang ◽

Yuan-Zheng Cheng ◽

Meng Qin ◽

Yong-Hong Wang ◽

Hong-Li Yu ◽

...

Keyword(s):

Drug Delivery ◽

Sustained Release ◽

Delivery System ◽

Drug Loading ◽

Great Promise ◽

Burst Release ◽

Bletilla Striata ◽

Vaginal Drug Delivery ◽

Thermosensitive Hydrogels

Thermosensitive hydrogels have increasingly received considerable attention for local drug delivery based on many advantages. However, burst release of drugs is becoming a critical challenge when the hydrogels are employed. Microspheres- (MS-) loaded thermosensitive hydrogels were thus fabricated to address this limitation. Employing an orthogonal design, the spray-dried operations of tenofovir (TFV)/Bletilla striata polysaccharide (BSP)/chitosan (CTS) MS were optimized according to the drug loading (DL). The physicochemical properties of the optimal MS (MS F) were characterized. Depending on the gelation temperature and gelating time, the optimal CTS-sodium alginate- (SA-) α,β-glycerophosphate (GP) (CTS-SA-GP) hydrogel was obtained. Observed by scanning electron microscope (SEM), TFV/BSP/CTS MS were successfully encapsulated in CTS-SA-GP. In vitro releasing demonstrated that MS F-CTS-SA-GP retained desirable in vitro sustained-release characteristics as a vaginal delivery system. Bioadhesion measurement showed that MS-CTS-SA-GP exhibited the highest mucoadhesive strength. Collectively, MS-CTS-SA-GP holds great promise for topical applications as a sustained-release vaginal drug delivery system.

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