Faster Drug Release Research Articles

Mouth Dissolving Film of Domperidone: An approach towards Formulation and its Evaluation

The objective of the current work is to formulate and evaluate the mouth dissolving film of domperidone. It is ideally suitable for the treatment of emesis. The mouth dissolving film of domperidone is useful in the vomiting through the journey. Mouth dissolving films were formulated by the solvent casting technique and its in-vitro as well as the in-vivo evaluation was done by the usual pharmacopoeial and unofficial tests and by using human volunteers. The main benefit of the preparation technique includes fewer operation units, better content consistency. The mouth dissolving film formed was found to be disintegrated in 1 minute. The ratio of components in the aqueous phase affected the thickness, drug content, tensile strength, percentage elongation, folding endurance, and release profile of mouth dissolving film and the best results were obtained for the HPMC E15 and polyethyleneglycol. The compatibility between domperidone and excipients was confirmed by FTIR and DSC studies. The developed mouth dissolving film of domperidone demonstrated usefulness for fast release of drug in mouth, for better drug utilization, and improved patient compliance. The optimized formulation, due to low HPMC E15 content, has optimum tensile strength and thickness. Formulation F8 containing HPMC E15 and PG showed a cumulative % drug release of 95.10 at the end of 12 minutes. HPMC E15 films showed higher cumulative % drug release than films of other HPMC E grades at different concentrations. It was found to be stable during the accelerated stability study. The effect of different concentrations of polymers and plasticizers on in-vitro evaluation parameters was evaluated. Hence, data showed that formulation F8 was the most suitable for the development of fast dissolving oral films of domperidone.

Phase transited asymmetric membrane floating nanoparticles: a means for better management of poorly water-soluble drugs.

Effective remedy to gastrointestinal (GI) side effects caused by poorly water-soluble drugs remains a challenge. Researching for novel techniques to reduce these side effects and increase patient adherence to medical treatment is of interest. The current study aims to develop an innovative nano-sized gastro-retentive drug delivery for better management of poorly water-soluble drugs. A non-disintegrating ibuprofen-asymmetric membrane floating nanoparticle (Ibuprofen-AMFNP) was prepared by phase inversion technique to increase the gastric residence of the drug. Powder characterization, solubility, in vitro buoyancy, effect on in vivo inflammatory markers, and polymer diffusibility studies were conducted on the prepared formulation. All UV-spectrophotometric analysis was accomplished through a fiber optic system. The prepared Ibuprofen-AMFNPs were in the nano range of 114.45nm ±1.31nm. The formulation was buoyant for 12h in the dissolution media indicating increased gastric residence, had better solubility and powder characteristics compared to the pure drug. Scanning electron microscopy revealed an outer non-porous and inner porous asymmetric membrane. Ibuprofen-AMFNP followed Higuchi drug release kinetics (p=0.9925) and had a Fickian diffusion release mechanism (n=0.05). Polymer diffusibility study showed that the 24h stored formulation had faster drug release with no lag time (-923.08nm/h) compared to a fresh formulation (2526.32nm/h). The prepared nano-formulation showed a higher percentage of anti-inflammatory (85.144%) effect compared to the pure drug (78.336%). Ibuprofen-AMFNP is envisioned to help reduce drug-related GI side effects, improve drug delivery, and thereby increase patient adherence to medical treatment.

Gas generating microspheres for immediate release of Hsp90 inhibitor aiming at postembolization hypoxia in transarterial chemoembolization therapy of hepatocellular carcinoma

CO2 gas generating poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) was designed for rapid release of tanespimycin (17-AAG) in transarterial chemoembolization (TACE) treatment of hepatocellular carcinoma (HCC). As poorly water-soluble drug is generally released from PLGA MS in a sustained manner, the drug release profile should be controlled according to its clinical indications. In current study, responding to immediate increase in hypoxia inducible factor-1α (HIF-1α) level under hypoxia state followed by embolization of tumor feeding arteries, sodium bicarbonate (NaHCO3) was added to PLGA/17-AAG MS for fast drug release by CO2 gas generation in slightly acidic tumor microenvironment. With the aid of NaHCO3, initial burst release of 17-AAG was available without losing the micron-size and spherical shape of designed MS for embolization of artery. Acid-responsive CO2 gas generation and subsequent immediate release of 17-AAG from MS were successfully verified. PLGA/17-AAG/NaHCO3 MS-treated group exhibited higher antiproliferation and apoptosis induction efficacies in McA-RH7777 and SNU-761 cells. McA-RH7777 tumor-implanted rats treated by TACE using PLGA/17-AAG/NaHCO3 MS presented a complete therapeutic response. All these findings suggest that developed tumor microenvironment-responsive gas-generating MS can be efficiently applied to TACE therapy of HCC.

Evaluation of the effect of carrier material on modification of release characteristics of poor water soluble drug from liquisolid compacts.

Liquisolid compact is a novel dosage form in which a liquid medication (liquid drug, drug solution/dispersion in non-volatile solvent/solvent system) is converted to a dry, free flowing powder and compressed. Objective of the study was to elucidate the effect of carrier material on release characteristics of clopidogrel from liquisolid compacts. Different formulations of liquisolid compacts were developed using microcrystalline cellulose, starch maize, polyvinyl pyrollidone and hydroxypropyl methylcellulose as carrier material in three concentrations (40, 30 and 20%, w/w). Liquid vehicle was selected on the basis of solubility of clopidogrel. Colloidal silicondioxide was used as coating material and ratio of carrier to coating material was kept 10. A control formulation comprised of microcrystalline cellulose (diluents), tabletose-80 (diluents), primojel (disintegrant) and magnesium stearate (lubricant) was prepared by direct compression technique and was used for comparison. All the formulations were evaluated at pre and post compression level. Acid solubility profile showed higher solubility in HCl buffer pH2 (296.89±3.49 μg/mL). Mixture of propylene glycol and water (2:1, v/v) was selected as liquid vehicle. Drug content was in the range of 99–101% of the claimed quantity. All the formulations showed better mechanical strength and their friability was within the official limits (<1%). Microcrystalline cellulose and starch maize resulted in faster drug release while polyvinyl pyrollidone and HPMC resulted in sustaining drug release by gel formation. It is concluded from results that both fast release and sustained release of clopidogrel can be achieved by proper selection of carrier material.

Drug transport kinetics of intravascular triggered drug delivery systems

Intravascular triggered drug delivery systems (IV-DDS) for local drug delivery include various stimuli-responsive nanoparticles that release the associated agent in response to internal (e.g., pH, enzymes) or external stimuli (e.g., temperature, light, ultrasound, electromagnetic fields, X-rays). We developed a computational model to simulate IV-DDS drug delivery, for which we quantified all model parameters in vivo in rodent tumors. The model was validated via quantitative intravital microscopy studies with unencapsulated fluorescent dye, and with two formulations of temperature-sensitive liposomes (slow, and fast release) encapsulating a fluorescent dye as example IV-DDS. Tumor intra- and extravascular dye concentration dynamics were extracted from the intravital microscopy data by quantitative image processing, and were compared to computer model results. Via this computer model we explain IV-DDS delivery kinetics and identify parameters of IV-DDS, of drug, and of target tissue for optimal delivery. Two parameter ratios were identified that exclusively dictate how much drug can be delivered with IV-DDS, indicating the importance of IV-DDS with fast drug release (~sec) and choice of a drug with rapid tissue uptake (i.e., high first-pass extraction fraction). The computational model thus enables engineering of improved future IV-DDS based on tissue parameters that can be quantified by imaging.

Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy.

BackgroundChemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy.MethodsA novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety.ResultsHES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice.ConclusionThe pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.

Enhanced photoacoustic effect for simultaneous imaging and drug release using phase-transition mesoporous silicon nanoprobe

Probe-assisted integration of imaging and therapy into a single modality provides tremendous opportunities in biological applications. In this study, phase-transition-mediated cavitation was used for simultaneous photoacoustic imaging (PA) and triggering drug release. For this purpose, we developed unique phase-transition mesoporous silicon nanoprobes (ICG/PFC/PTX@MSNs) consisting of indocyanine green (ICG), perfluorocarbon (PFC), and paclitaxel (PTX). For high-dose laser irradiation, the encapsulated ICG absorbs laser energy, providing localized heating well over the supercritical temperature of PFC. Then, liquid PFC was subjected to a liquid-to-gas phase transition, which generated stronger PA signals and promoted fast drug release. The enhancement of ICG/PFC/PTX@MSNs for PA imaging was demonstrated in in vitro and in vivo experiments. The average PA signal based on the phase-transition mechanism was ∼3 times higher than that of the traditionally used thermal expansion mechanism. Furthermore, the rapid drug release based on the same phase-transition-mediated cavitation mechanism can be achieved simultaneously; eventually, ∼80.4% of the total encapsulated drug were released. The hematoxylin–eosin stained section of tumor tissues from the ICG/PFC/PTX@MSN group showed many dead cells with condensed nuclei and pyknosis. This method not only promotes efficacy of chemotherapy but also makes accurate imaging-guided chemotherapy possible.

Characterization and Optimization of Oral Solid Supersaturable Self-emulsifying Drug Delivery System of Cilostazol

Objective: This study aimed to prepare tablets containing solid supersaturable self-emulsifying drug delivery system (S-SEDD) of cilostazol for oral use. Method: To improve drug dissolution and so bioavailability for cilostazol (calss II drug) as well as reducing the amount of additives (except for drug =50 mg), liquid S-SEDD of cilostazol were prepared. In this study the liquid supersaturable formula was converted into a solid supersaturable self-emulsifying form using different amounts of two different types of the adsorbents (avicel 101 and aerosil 200). Accordingly; six-formulas (SS1-SS6) were prepared and evaluated applying pre-compression evaluation and the best formula was SS3 formula having an amorphous homogenous free-flowing property and used to prepare tablets using direct compression method. Consequently; six tablet formulas (T1-T6) containing different types and amounts of additives were prepared and evaluated applying post-compression parameters and in-vitro drug release. Result: The best tablet formula was T2 formula which showed high dissolution profile under sink and non-sink condition in comparison to conventional marketed tablet indicating that it kept its supersaturable self-emulsification in-vitro with faster drug release which may lead to improve drug absorption and bioavailability with a fast onset of action. Conclusion: This work succeeded in converting the prepared cilostazol liquid S-SEDD to solid SEDD which is compressed into an immediate release tablets that disintegrate and spontaneously emulsified to form supersaturable system in the GIT which improved drug solubility, release and consequently may enhance its absorption and bioavailability leading to reducing dose size and drug/excipient size effects.

Self-assembled micelle responsive to quick NIR light irradiation for fast drug release and highly efficient cancer therapy

Upconversion nanoparticles (UCNPs) have been used for designing near infrared (NIR) light-responsive nanocarriers and controllable drug release. However, the need for long-term NIR light irradiation over hours impaired their application efficiency. Here we develop a self-assembled micelle of amphipathic polymer P-DASA which degrades via quick NIR light irradiation. UCNPs and DOX are also encapsulated in the micelle for quick drug release. P-DASA is composed of hydrophilic polyethylene glycol segment and photo-responsive hydrophobic donor–acceptor Stenhouse adduct (DASA). Only 5-min NIR irradiation causes the hydrophilicity conversion of P-DASA and the complete disruption of micelle with DOX fast release of 83.7% in 30 min to achieve highly efficient therapy. Moreover, the P-glycoprotein mediated DOX efflux is also diminished by concomitantly producing NO intracellularly. This micelle demonstrates impressive in vivo therapeutic effect, and thus provides an avenue for highly efficient cancer therapy.

Enhanced Eradication of Mucin-Embedded Bacterial Biofilm by Locally Delivered Antibiotics in Functionalized Microcontainers.

Bacterial biofilm-related infections are difficult to eradicate and require repeated treatments with high doses of antibiotics. Thus, there is an urgent need for new treatment strategies that minimize the use of antibiotics while enhancing biofilm eradication. Functionalized reservoir-based microdevices, such as, microcontainers (MCs), offer, high drug loading capacity, mucus embedment, and tuneable drug release. Here, MCs are loaded with the antibiotic ciprofloxacin (CIP), and sealed with a lid consisting of chitosan (CHI) and a mucolytic agent, N-acetylcysteine (NAC). It is found that CHI and NAC work synergistically, showing improved mucoadhesive and mucolytic properties. To better mimic the in vivo habitat of Pseudomonas aeruginosa (P.aeruginosa), the biofilm is grown in a mucin-containing medium on a newly developed centrifugal microfluidic system. The CHI/NAC coated MCs improve eradication of biofilm (88.22 ± 2.89%) compared to CHI-coated MCs (72.68 ± 3.73%) or bolus injection (39.86 ± 13.28%). The findings suggest that MCs are significantly more efficient than a bolus treatment. Furthermore, CHI/NAC functionalized MCs kill most of the biomass already after 5 h (80.75 ± 3.50%), mainly due to a fast drug release. This is the first time that CHI/NAC has been combined as a coating to explore mucolytic properties on bacterial biofilms.

Evaluation of solid carvedilol-loaded SMEDDS produced by the spray drying method and a study of related substances

In this study, various formulations of solidified carvedilol-loaded SMEDDS with high SMEDDS loading (up to 67% w/w) were produced with the spray drying process using various porous silica-based carriers. The process yield was improved with higher atomization gas flow rate during the spray drying process and with prolonged mixing time of dispersion of liquid SMEDDS and solid porous carriers prior to the spray drying process. Depending on the choice of the carrier and the SMEDDS:carrier ratio in solid SMEDDS, different drug loading, self-microemulsifying properties, drug release rates, and released drug fractions were obtained. The products exhibited fast drug release due to preserved self-microemulsifying properties and the absence of crystalline carvedilol, which was confirmed with XRD and Raman mapping. A decrease in drug content during the stability study was observed and investigated. This was at least partially attributed to the chemical degradation of the drug. Key degradation products determined by the LC-MS method were amides formed by in situ reaction of carvedilol with fatty acids present in the oily phase of SMEDDS.

Mini-review on Natural Disintegrants in Pharmaceutical Formulations

Disintegrants are agents which are integrated to tablets and some encapsulated formulations in order to promote the breakup of the tablet and capsule “slugs” into more small fragments in an aqueous environment which thereafter increment the available surface area and promoting a more rapid release of the drug substance. The development of new excipients for potential use as disintegrant agent in tablet formulations continues to be of interest. This is because different disintegrant agents can be useful in promoting penetration of moisture and dispersion of the tablet matrix and disintegration of tablet has received considerable attention at present as an essential step in obtaining fast drug release. Natural polymers such as starches, gums, mucilage, and dried fruits utilized as binder, diluent, and disintegrants to increase the solubility of poorly water-soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural disintegrants are safe and economical than synthetic disintegrants such as Polyvinylpyrrolidone (PVP). Therefore, in the present review, an attempt has been made to reveal the importance of the natural disintegrants in the pharmaceutical formulations.

DNA-Scaffolded Disulfide Redox Network for Programming Drug-Delivery Kinetics.

In response to specific stimuli, dynamic covalent materials enable the generation of new structures by reversibly forming/breaking chemical bonds, thus showing great potential for application in controlled drug release. However, using dynamic covalent chemistry to program drug-delivery kinetics remains challenging. Herein, an in situ polymerization-generated DNA-scaffolded disulfide redox network (DdiSRN) is reported in which nucleic acids are used as a scaffold for dynamic disulfide bonds. The constructed DdiSRN allows selective release of loading cargos inside cancer cells in response to redox stimuli. Moreover, the density of disulfide bonds in network can be tuned by precise control over their position and number on DNA scaffolds. As a result, drug-delivery kinetics can be programmed with a half-life, t1/2 , decreasing from 8.3 to 4.4 h, thus facilitating keeping an adequate drug concentration within the therapeutic window. Both in vitro and in vivo studies confirm that co-delivery of DOX and siRNA in combination with fast drug release inside cells using this DdiSRN enhances the therapeutic effect on multidrug-resistant cancer. This nontrivial therapeutic platform enabling kinetic control provides a good paradigm for precision cancer medicine.

Facile fabrication of multi-pocket nanoparticles with stepwise size transition for promoting deep penetration and tumor targeting

BackgroundNanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy.ResultsThe multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (< 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm3) bearing mice with reduced side effect.ConclusionsOur facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy.Graphic

Novel pegylated liposomal formulation of docetaxel with 3-n-pentadecylphenol derivative for cancer therapy

The taxanes are commonly used in the treatment of many types of cancer. The disadvantages of using taxanes in therapy are their low solubility in water, the toxicity or relatively poor pharmacokinetics of existing formulations. Using liposomes as carriers would help in overcoming these problems, however, their use is limited by the low incorporation efficiency of taxane molecules within bilayer and by subsequent drug crystallization. Most of published taxanes liposomal formulations use natural soy phosphatidylcholine (PC) as main liposomes lipid. This allows a relatively good drug retention during the liposomes storage, but on the other hand, the use of liposomes with more liquid bilayer facilitates fast drug release after its intravenous administration. In order to decrease the drug release from liposomes in circulation, we used pegylated HSPC (hydrogenated soy PC) liposomes containing a novel synthetic 3-n-pentadecylphenol derivative – KW101, that showed a remarkably stabilizing action for the docetaxel (DTX) dopped HSPC liposomes over 30 days, expressed by the inhibition of DTX crystallization. The resulting liposomes with DTX showed similar cytotoxicity on MCF-7 and MDA-MB-231 breast cancer cell lines and higher toxicity in drug-resistant NCI/ADR-RES cell line in comparison with the free DTX. Moreover, this formulation has good pharmacokinetics in mice, in comparison to control pegylated DTX formulation composed of egg phosphatidylcholine (ePC). This novel liposomal formulation of docetaxel consisting of HSPC with the stabilizing compound KW101, appears to be a promising carrier for DTX cancer therapy.

Muscle Tissue as a Surrogate for In Vitro Drug Release Testing of Parenteral Depot Microspheres

Despite the importance of drug release testing of parenteral depot formulations, the current in vitro methods still require ameliorations in biorelevance. We have investigated here the use of muscle tissue components to better mimic the intramuscular administration. For convenient handling, muscle tissue was used in form of a freeze-dried powder, and a reproducible process of incorporation of tested microspheres to an assembly of muscle tissue of standardized dimensions was successfully developed. Microspheres were prepared from various grades of poly(lactic-co-glycolic acid) (PLGA) or ethyl cellulose, entrapping flurbiprofen, lidocaine, or risperidone. The deposition of microspheres in the muscle tissue or addition of only isolated lipids into the medium accelerated the release rate of all model drugs from microspheres prepared from ester-terminated PLGA grades and ethyl cellulose, however, not from the acid-terminated PLGA grades. The addition of lipids into the release medium increased the solubility of all model drugs; nonetheless, also interactions of the lipids with the polymer matrix (ad- and absorption) might be responsible for the faster drug release. As the in vivo drug release from implants is also often faster than in simple buffers in vitro, these findings suggest that interactions with the tissue lipids may play an important role in these still unexplained observations.

Pluronic F-127/Silk Fibroin for Enhanced Mechanical Property and Sustained Release Drug for Tissue Engineering Biomaterial.

Herein, an injectable thermosensitive hydrogel was developed for a drug and cellular delivery system. The composite was prepared by facile physical mixing of pluronic F-127 (PF) and silk fibroin (SF) in an aqueous solution. The chemical structure, transparency, viscosity, injectability, degradation kinetic, cumulative release of dexamethasone (Dex), a type of corticosteroid drug, and size distribution of the fabricated hydrogels were characterized. Cytotoxicity of the hydrogels was also studied to verify the biocompatibility of the hydrogels. The addition of a proper amount of SF to PF not only improved the mechanical strength but also decreased the degradation rate which improved the fast rate release of hydrophobic drugs. The cytotoxicity of the hydrogel decreased when SF was added to PF in a proper amount. Overall, the results confirm that the composite of PF and SF can be a promising cell and drug delivery system for future application in tissue engineering and regenerative medicine.

CD47-mediated DTIC-loaded chitosan oligosaccharide-grafted nGO for synergistic chemo-photothermal therapy against malignant melanoma

Nano-graphene oxide (nGO), an effective drug nanocarrier, is used for simultaneous photothermal therapy (PTT) and near-infrared fluorescence imaging. Dacarbazine (DTIC) is used in the treatment of melanoma with limited clinical efficacy. PTT shows promise in the treatment of skin cancer. Herein, chitosan oligosaccharide (COS)-grafted nGO was further modified with CD47 antibody, and loaded DTIC was prepared using a versatile nanoplatform (nGO-COS-CD47/DTIC) for the treatment of melanoma as a synergistic targeted chemo-photothermal therapy. The in vitro results demonstrated that nGO-COS-CD47/DTIC nanocarriers have excellent biocompatibility, photothermal conversion efficiency, high targeting efficiency, fast drug release under NIR irradiation, and tumor cell killing efficiency. Notably, nGO-COS-CD47/DTIC plus NIR irradiation significantly promoted early cell apoptosis through the mitochondrial apoptosis pathway and exhibited a significant joint function of antitumor efficacy. The demonstrated nGO-COS-CD47/DTIC can provide a highly efficient malignant melanoma therapy using this multifunctional intelligent nanoplatform.

Sustainable preparation of anti-inflammatory atorvastatin PLGA nanoparticles

In the present study, the anti-inflammatory lipophilic drug atorvastatin was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) using a sustainable method in comparison to the standard emulsion-diffusion-evaporation technique. For the sustainable method the organic solvent ethyl acetate was fully replaced by 400 g/mol poly(ethylene glycol) (PEG 400). Both techniques led to the formation of nanoparticles with comparable sizes of about 170 to 247 nm depending on the polymer type, with monomodal size distribution and negative zeta potential. All nanoparticles demonstrated a high biocompatibility in a shell-less hen’s egg model and displayed an anti-inflammatory effect in human monocytes. The use of PEG 400 resulted in plasticizing effects and a lower crystallinity of the PLGA nanoparticles as determined by differential scanning calorimetry and Raman spectroscopy, which correlated with a faster drug release. Interestingly, the particles prepared by the sustainable method showed a crystallinity and drug release kinetics similar to nanoparticles made of PEG-PLGA using the standard method. Conclusively, the sustainable method is a fast and easy to perform technique suitable to prepare atorvastatin-loaded PLGA nanoparticles avoiding toxic and environmentally damaging drawbacks frequently associated with classical organic solvents.

Efficacy of pH-Sensitive Nanomedicines in Tumors with Different c-MYC Expression Depends on the Intratumoral Activation Profile.

Effective inhibition of the protein derived from cellular myelocytomatosis oncogene (c-Myc) is one of the most sought-after goals in cancer therapy. While several c-Myc inhibitors have demonstrated therapeutic potential, inhibiting c-Myc has proven challenging, since c-Myc is essential for normal tissues and tumors may present heterogeneous c-Myc levels demanding contrasting therapeutic strategies. Herein, we developed tumor-targeted nanomedicines capable of treating both tumors with high and low c-Myc levels by adjusting their ability to spatiotemporally control drug action. These nanomedicines loaded homologues of the bromodomain and extraterminal (BET) motif inhibitor JQ1 as epigenetic c-Myc inhibitors through pH-cleavable bonds engineered for fast or slow drug release at intratumoral pH. In tumors with high c-Myc expression, the fast-releasing (FR) nanomedicines suppressed tumor growth more effectively than the slow-releasing (SR) ones, whereas, in the low c-Myc tumors, the efficacy of the nanomedicines was the opposite. By studying the tumor distribution and intratumoral activation of the nanomedicines, we found that, despite SR nanomedicines achieved higher accumulation than the FR counterparts in both c-Myc high and low tumors, the antitumor activity profiles corresponded with the availability of activated drugs inside the tumors. These results indicate the potential of engineered nanomedicines for c-Myc inhibition and spur the idea of precision pH-sensitive nanomedicine based on cancer biomarker levels.