Figure - available from: Pharmaceutical Research
This content is subject to copyright. Terms and conditions apply.
The response surface plots showing the interactive effects of X1 and X2 (a) X1 and X3 (b) X2 and X3 (c) on the response DL (%) (drug loading). X1, X2 and X3 represent the content of F68, ratio of PLGA/ mPEG-PLGA, and the ratio of acetate/benzyl alcohol, respectively.
Source publication
PurposeTo prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. MethodsPRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) we...
Citations
... Such preparations comprise both oily solutions (e.g., estradiol and testosterone) and aqueous suspension forms (e.g., penicillin G procaine and methylprednisolone). Moreover, some drugs, including peptides and proteins, have been formulated as emulsions, suspensions, liposomes, and even nanoparticles for IM injection to achieve adequate pharmacokinetic profiles for each active ingredient (Hwang et al. 2016;Xie et al. 2018). ...
... Lipid coating PLGA nanoparticles system (lipid nanoparticles, LNPs) has not only combined the advantages of polymer nanoparticles and liposomes but efficiently avoided the defects of them (Muller and Keck, 2004;Alavi et al., 2017). The dual advantages of the particles and vesicle make it an excellent oral drug carrier with high biocompatibility and sustained release (Xie et al., 2018). In this system, drugs can be efficiently encapsulated in the nanoparticles core and/or the lipid bilayers, resulted in increased drug load capability. ...
Drugs are administered orally in the clinical treatment of hypertension. Antihypertensive peptides have excellent angiotensin converting enzyme inhibitors activity in vitro. However, the poor oral bioavailability and therapeutic effect of antihypertensive peptides were mainly caused by rapid degradation in gastrointestinal and the short circulation time in blood, which remain to be further optimized. Therefore, the novel oral peptide delivery system is urged to improve the oral absorption and efficacy of peptide drugs. In this work, Tyr-Gly-Leu-Phe (YF4)-loaded lipid nanoparticles (YF4-LNPs) combined the advantages of polymer nanoparticles and liposomes were developed, which could greatly enhance the oral bioavailability and ameliorate the sustained release of peptide drug. YF4 loaded nanoparticles (YF4-NPs) were firstly prepared by a double-emulsion internal phase/organic phase/external phase (W1/O/W2) solvent evaporation method. YF4-NPs were further coated by membrane hydration-ultrasonic dispersion method to obtain the YF4-LNPs. The optimal YF4-LNPs showed a small particle size of 227.3 ± 3.8 nm, zeta potential of -7.27 ± 0.85 mV and high entrapment efficiency of 90.28 ± 1.23%. Transmission electronic microscopy analysis showed that the core-shell lipid nanoparticles were spherical shapes with an apparent lipid bilayer on the surface. Differential scanning calorimetry further proved that YF4 was successfully entrapped into YF4-LNPs. The optimal preparation of YF4-LNPs exhibited sustained release of YF4 in vitro and a 5 days long-term antihypertensive effect in vivo. In summary, the lipid nanoparticles for oral antihypertensive peptide delivery were successfully constructed, which might have a promising future for hypertension treatment.
... penicillin G procaine, methylprednisolone). Moreover, some drugs, including peptides and proteins, have been formulated as emulsions, suspensions, liposomes and even nanoparticles for IM injection, in order to achieve adequate pharmacokinetic profiles for each active ingredient (Hwang et al., 2016;Xie et al., 2018). ...
Systemic absorption of a drug depends on its physicochemical properties, the nature of the dosage form on which it is included and the anatomical and physiological characteristics of the site of absorption. These considerations are important on the biopharmaceutical production and evaluation of drugs: the design of the dosage forms requires a deep knowledge of the physiological and pathological factors that affect drug absorption for guarantying the therapeutic efficacy and to avoid possible drug-drug and drug-nutrient interactions.
Purpose
Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres.
Methods
This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release.
Results
The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague–Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%.
In conclusion
In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.
Graphical Abstract
Progesterone is a natural steroidal sex hormone in the human body, mainly secreted through the adrenal cortex, ovary, and placenta. In humans, progesterone is essential for endometrium transformation in the uterus at the time of ovulation and maintenance of pregnancy. When the body cannot produce enough progesterone for specific ailments, it is administered via different routes such as oral, vaginal, transdermal, topical, parental, and intranasal routes. Although progesterone is commercially available in multiple conventional formulations, low solubility, less permeability and extensive hepatic first-pass metabolism are the major constraints to its delivery. These challenges can be overcome substantially by formulating progesterone into novel delivery systems like lipid carriers, polymeric carriers, hydrogels, several nanocarriers, depot and controlled release systems. Various research papers and patents have been published in the last two decades on progesterone delivery systems; clinical studies were conducted to establish safety and efficacy. This review is focused on the pharmacodynamic and pharmacokinetic parameters of progesterone, its delivery constraints, and various advanced delivery systems of progesterone.
Drug microcrystal (MC) is an important category of long acting injections (LAIs), whose release profile is controlled mainly by particle size, crystal form, drug solubility, and other parameters. In this study, a polymeric H⁺ depot composed of alginate was combined with drug MC using ginkgolide B (GB) as model drug to reduce the initial burst release of the drugs with elevated solubility in body fluid. The parameters of GB MC preparation by precipitation, including stabilizer type and amount, phase volume ratio, and stirring rate were investigated. And the particle size/distribution, particle morphology, crystallinity, in vitro release of optimized GB MC were characterized. The in vivo dissolution retardation effect of acidified alginate (SAA) was first confirmed by live imaging using fluorescein as probe. And the pharmacokinetic profiles of different GB MC-polymer blends were investigated by UPLC-MS/MS. The prepared GB MC was spherical-like particles with a mean particle size of 5.863 μm and a span value of 1.634. The crystallinity of GB MC was lowered by the precipitation process compared with that of the crude drug, which resulted in a faster in vitro dissolution with more than 90% of drugs dissolved in 20 min. When administered with SAA, an alginate amount-dependent reduction in Cmax (1243.5 ± 281.4 ng/mL of GB-SAA, 1:5, 820.9 ± 84.0 ng/mL of GB-SAA, 1:10, 2850.9 ± 1059.3 ng/mL of GB alone and 2476.9 ± 396.4 ng/mL of GB-HPMC E5, 1:10) and prolongation in Tmax (3.2 ± 1.1 h of GB-SAA, 1:5, 6.4 ± 2.2 h of GB-SAA, 1:10, 1.2 ± 0.45 h of GB alone and 1.4 ± 0.55 h of GB-HPMC E5, 1:10) was noticed, indicating the capability of polymeric H⁺ depot in controlling GB release in vivo. In conclusion, the polymeric H⁺ depot strategy influenced drug dissolution and outward drug diffusion sequentially to retard the initial burst release of drugs with elevated solubility in body fluid.
Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) have attracted considerable interest in the medical community as a sustained-release drug delivery system for localized treatment. However, it is currently a grand challenge to simultaneously achieve low-dose drugs, stable and prolonged drug release, and long-term retention circumventing uptake by macrophages. Here, we construct a solvent-exchange in-situ depot system by incorporating progesterone (PRG) loaded PLGA NPs into a sucrose acetate isobutyrate (SAIB) and PLGA matrix for the long term treatment of Assisted Reproductive Technology (ART). The results showed that different solvent and PLGA contents could affect the drug release rate of PRG NPs-SAIB-PLGA in-situ depot system (PSPIDS). When DMSO was used as solvent with the addition of 8% PLGA to the depot, PSPIDS could achieve a constant drug release with no burst for 2 weeks in vitro. After a single intramuscular injection, such PSPIDS showed higher drug concentration and AUC (6773.0±348.8μg/L·h) over the entire 7-day testing period compared with the commercial multiple-day-dosing intramuscular PRG-oil solution (1914.5±180.7μg/L·h) in vivo. Importantly, PSPIDS could be administered at a dose of 3.65mg/kg, which was one fourth of dose required for PRG-oil solution. The results demonstrate that PRG NPs could successfully achieve both reduced administered dosage and burst release, and therefore that PSPIDS is a promising long-acting composite system for hydrophobic drugs.
The use of nanoparticles in medicine has improved the options for diagnosis and therapy. Numerous diseases that were previously thought to be challenging are now addressed with the advent of nanoparticles. This is possible due to the ability of nanoparticles to selectively target desired tissue/cells and communicate with the cellular environment at nanoscale levels. Although nanomedicine has innumerous advantages over traditional medicine, the use of nanoparticles comes with its own baggage of special pharmacokinetic parameters and toxicity. Hence it becomes imperative to understand the development of nanoparticles from bench to clinic with emphasis on its pharmacokinetic properties and toxicity. With this objective in mind we have discussed the synthesis of clinically important metallic and nonmetallic nano-drug carriers and the process to alter their physicochemical properties for their application in therapy and/or diagnosis. This is followed by a discussion of the pharmacokinetic properties of selected nano-drug carriers that make them desirable for formulations as an efficient drug delivery system. Lastly, the chapter discusses potential toxicities that are associated with nanocarriers, mechanisms of toxicity, major target organs, and factors influencing these toxicities. We have concluded this chapter by discussion of two clinically used nano-drug carriers.
Poly(lactic-co-glycolic acid) (PLGA) is the most commonly described biocompatible copolymer used in biomedical applications. In this work, a green synthetic approach based on the biocompatible zinc proline complex, as an initiator for PLGA synthesis, is reported for the first time for the synthesis of methoxy-poly(ethylene glycol)-block-poly(L-lactic-co-glycolic acid) (mPEG–PLGA). mPEG–PLGA with controlled molecular weight and narrow polydispersity was synthesised. Its potential for delivery of irinotecan (Ir), a poorly water-soluble chemotherapeutic drug used for the treatment of colon and pancreatic cancer, was studied. Nanoparticles of controlled size (140–160 nm), surface charge (∼−10 mV), release properties and cytotoxicity against CT-26 (colon) and BxPC-3 (pancreatic) cancer cells, were prepared. Tumor accumulation was confirmed by optical imaging of fluorescently labelled nanoparticles. Unlike Tween® 80 coated NP-Ir, the Pluronic® F-127 coated NP-Ir exhibits significant tumor growth delay compared to untreated and blank formulation treated groups in the CT-26 subcutaneous tumor model, after 4 treatments of 30 mg irinotecan per kg dose. Overall, this proof-of-concept study demonstrates that the newly synthesized copolymer, via a green route, is proven to be nontoxic, requires fewer purification steps and has potential applications in drug delivery.
