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1.
Drug Deliv ; 29(1): 284-293, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35019794

RESUMO

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 µg/cm2.h, and MIC of 0.44 µg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.


Assuntos
Aloe/química , Alopecia/patologia , Finasterida/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas/química , Origanum/química , Administração Cutânea , Animais , Química Farmacêutica , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Álcoois Graxos/química , Finasterida/administração & dosagem , Masculino , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Ratos , Ratos Wistar , Absorção Cutânea , Solubilidade , Propriedades de Superfície
2.
Drug Deliv ; 29(1): 254-262, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35014929

RESUMO

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p < .05) higher for MZ-SO NLC (1472 µg/cm2) as compared with a marketed MZ formulation (1215 µg/cm2) and an aqueous MZ suspension (470 µg/cm2). Additionally, an in vivo efficacy study in terms of the ulcer index against C. albicans found a superior result for the optimized MZ-SO NLC (0.5 ± 0.50) in a treated group of animals. Hence, it can be concluded that MZ, through an optimized NLC of SO, can treat candidiasis effectively by inhibiting the growth of C. albicans.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Miconazol/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas/química , Óleo de Gergelim/química , Animais , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Química Farmacêutica , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Lipídeos/química , Masculino , Miconazol/administração & dosagem , Miconazol/farmacocinética , Mucosa Bucal , Tamanho da Partícula , Distribuição Aleatória , Ratos , Ovinos , Solubilidade , Propriedades de Superfície
3.
Int J Nanomedicine ; 16: 5465-5478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413644

RESUMO

INTRODUCTION: Natural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation's aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health. METHODS: Several OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities. RESULTS: The NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats. CONCLUSION: This study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.


Assuntos
Microbiota , Origanum , Animais , Sistemas de Liberação de Medicamentos , Emulsões , Ratos , Tensoativos
4.
Drug Deliv ; 28(1): 741-751, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33840320

RESUMO

The majority of newly developed drugs need to be incorporated with delivery systems to maximize their effect and minimize side effects. Nanoemulsions (NEs) are one type of delivery system that helps to improve the solubility and dissolution of drugs, attempting to enhance their bioavailability and onset of action. The objective of this investigation was to develop an omega-3 oil-based NE loaded with loxoprofen (LXP) to enhance its dissolution, in vitro release, and mucosal penetration and decrease its mucosal ulcerative effects when applied in an oral treatment. LXP-loaded NEs were formulated with varying levels of omega-3 oil (10-30%), surfactant polyoxyethylene-C21-ethers (laureth-21) (40-60%), and co-surfactant polyethylene glycol-40 hydrogenated castor oil (HCO-40) (30-50%) using an extreme vertices mixture design. The developed NEs were characterized for globule size and drug loading capacity. The optimal formulation was tested for in vitro drug release, ex vivo permeation, and ulcer index value. The developed NE acquired a globule size ranging 71-195 nm and drug loading capacity of 43-87%. Considering the results of the in vitro release study, the optimized NE formulation achieved 2.45-fold and 2-fold increases in drug permeation across tested mucosa compared to a marketed tablet and drug aqueous dispersion, respectively. Moreover, the optimum NE exhibited the best ulcer index in comparison to drug aqueous suspension and different formulations when tested in rats. Overall, this research highlights the capacity of NEs to deliver LXP with enhanced solubility, drug release, and permeation while effectively protecting the application site from side effects of the model drug.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ácidos Graxos Ômega-3/química , Nanopartículas/química , Fenilpropionatos/farmacologia , Odontalgia/tratamento farmacológico , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacocinética , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emulsões/química , Masculino , Fenilpropionatos/administração & dosagem , Fenilpropionatos/efeitos adversos , Fenilpropionatos/farmacocinética , Ratos , Ovinos , Absorção Cutânea/fisiologia , Solubilidade , Tensoativos
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