Drug Delivery Letters - Volume 15, Issue 1, 2025
Volume 15, Issue 1, 2025
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Lipid Drug Conjugates in Pharmaceutical Formulations and Drug Delivery Systems
More LessAuthors: Chitrali Talele, Dipali Talele, Niyati Shah, Mamta Kumari, Piyushkumar Sadhu and Chintan AundhiaDrugs that have been covalently altered with lipids are known as lipid-drug conjugates. Drug characteristics are altered and their lipophilicity is increased when lipids are conjugated to drug molecules. The conjugates exhibit a number of benefits, including increased oral bioavailability, improved lymphatic targeting, improved tumor targeting, and reduced cytotoxicity. Different conjugation techniques and chemical bridges can be utilized to create lipid-drug conjugates depending on the chemical makeup of medicines and lipids. For lipid-drug conjugates to function at their best, linkers and/or conjugation techniques are essential. They control how medications are released from lipid-drug conjugates. The numerous lipids utilized to make lipid-drug conjugates and the various conjugation techniques are outlined in this article. Although these conjugates can be delivered without a delivery vehicle, many of them are put into suitable delivery techniques. Drug loading into lipophilic parts of vehicles can be considerably improved by the lipid component in the conjugates, leading to combinations with significant drug content and superior stability.
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Novel Delivery Systems of Raloxifene Hydrochloride for Improved Bioavailability and Therapeutic Efficacy: A Review
More LessAuthors: Shashank Chaturvedi and Richa SharmaRaloxifene hydrochloride belongs to the selective estrogen receptor modulator category. Initially, US FDA approved its use for the prevention and treatment of osteoporosis in post-menopausal women. Later, raloxifene hydrochloride was also approved for the prevention of invasive breast carcinoma in post-menopausal women under the high-risk category. Despite its immense and diverse therapeutic potential, the oral bioavailability of raloxifene hydrochloride is only ~ 2%. The factors responsible for the poor bioavailability of raloxifene hydrochloride include its amphiphobic nature, para-glycoprotein pump-mediated efflux in the intestine, and high pre-systemic glucuronidation. In the past two decades, multiple novel delivery systems, viz. lipid-based nanocarriers, polymeric nanoparticles, polymer-lipid hybrid nanoparticles, micelles, and mixed micelles, have been developed to overcome its drawbacks. Moreover, inclusion complex, phospholipid complex, and solid dispersion have also been developed to improve its solubility and dissolution rate. Further, some research groups successfully explored non-peroral routes like nasal and transdermal for augmenting the raloxifene hydrochloride bioavailability and its therapeutic efficacy. Hence, the principal objective of this review paper is to critically analyze all the delivery systems developed for raloxifene hydrochloride with their advantages and limitations. In addition, a detailed discussion of the physicochemical and pharmacokinetic parameters of raloxifene hydrochloride has been included in this paper. An in-depth understanding of these parameters will assist formulation scientists in developing efficient delivery systems in the future. In conclusion, the literature review revealed that the nanoparticulate systems successfully augmented the raloxifene hydrochloride bioavailability and therapeutic efficacy in pre-clinical experiments. However, future clinical trials should be conducted to assess their safety and therapeutic efficacy for rapid pre-clinical to clinical translation.
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Preparation and Characterization of Silver Sulfide Nanoparticle (Ag2S)-coated Chitosan for the Delivery of Methotrexate
More LessAuthors: Nazaninzahra Maghami and Masoud MokhtaryBackgroundThe preparation of nanoparticles with the efficiency of treatment and diagnosis at the same time has received more and more attention in recent years. Metal nanoparticles are one of the best candidates for this purpose.
MethodsSilver sulfide nanoparticle (Ag2S) coated with chitosan was synthesized and then methotrexate was loaded, and then the anticancer property of the synthesized nanoparticles was examined on the cancer cells. Synthesized nanoparticles were characterized using DLS, TEM, FTIR, XRD and UV-Vis techniques. Then, the hemolytic activity of synthesized nanoparticles was evaluated using human red blood cells. Finally, the anticancer effect of synthesized nanoparticles on 4T1 cancer cells was investigated. In this study, Ag2S@CS nanoparticles were synthesized using the mineralization method. Next, methotrexate was loaded in the synthesized nanoparticles. Ag2S@CS-MTX nanoparticles have an average size of approximately 24.02 ± 6.5 nm, with a spherical shape.
ResultsThe synthesized nanoparticles showed a hydrodynamic size of 119.9 nm. The size obtained from DLS analysis is slightly larger than the size obtained from TEM analysis for Ag2S@CS-MTX nanoparticles. Ag2S@CS-MTX nanoparticles have a negative surface charge and tend to repel each other, so they do not show a tendency to aggregate, for this reason it can provide colloidal stability.
ConclusionExamining the toxicity effect of synthesized nanoparticles on 4T1 cell line showed that Ag2S@CS nanoparticles had no significant toxicity effect on 4T1 cell line, but Ag2S@CS-MTX system showed significant toxicity with increasing concentration.
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Optimizing Dermal Delivery of Linezolid for Treating Skin and Soft Tissue Infections: NLC-based Gel Formulation using Taguchi Design
More LessAuthors: Iti Chauhan and Lubhan SinghBackgroundUncomplicated skin and soft tissue infections account for approximately 200 million visits to ambulatory care settings annually. Linezolid (LNZ) is an oxazolidinone that has proven its effectiveness in combating skin and soft tissue infections caused by gram-positive pathogens. LNZ is administered via oral suspension, tablets, or an intravenous route in most instances. However, its extended therapy leads to undesirable side effects like diarrhoea, thrombocytopenia, myelosuppression, lactic acidosis, etc. and even life-threatening complications. The dermal administration of LNZ offers an alternative route, ensuring localized and sustained release at the site of infection. This approach may reduce systemic exposure and allow for lower doses compared to oral ingestion, which can decrease the risk of adverse effects.
ObjectivesThis research aimed to develop a nanostructured lipid carrier (NLC)-based gel for delivering LNZ via the dermal route to treat uncomplicated skin and soft tissue infections.
MethodsNLC were developed by high-shear homogenisation and sonication method using glyceryl trimyristate as a solid lipid and neem oil as a liquid lipid. The Taguchi design was employed to optimize NLCs using surfactant concentration (mg), drug-to-lipid ratio, and sonication time (sec) as independent variables. Their effect on particle size, zeta potential, and entrapment efficiency was studied. The optimized nanocarriers were developed into a gel product and evaluated for drug release, permeation, and antibacterial activity.
ResultsThe optimised process parameters to attain outcomes were 2% surfactant, 1:1 drug-to-lipid ratio and 300 seconds of sonication. The resulting NLC had an average size of 191.2 ± 2.76 nm, a zeta potential of -30.7 ± 4.50 mV, and 84.89 ± 2.76% drug entrapment. NLC-based gel displayed anomalous transport with a 90.16% drug release. The gel showed a strong antibacterial effect against Staphylococcus aureus with a 7.57 ± 0.12 cm mean zone of inhibition. Ex-vivo skin permeation studies revealed 24.19 ± 0.19% drug permeation and 64.46 ± 0.58% cutaneous deposition. NLC-based gel demonstrated a significant decrease in colony-forming units in infected animal models.
ConclusionThe ex-vivo investigations demonstrated the presence of LNZ at the infection site, enhancing therapeutic effectiveness. In vitro and in-vivo findings illustrated the substantial antibacterial efficacy of LNZ NLC-based gel. The adoption of NLC-based gel exhibits promising potential as a carrier for dermal delivery of LNZ.
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