**4. Conclusions**

The solubility of clarithromycin in various lipid and surfactants was studied, and based on solubility criteria, stearic acid (lipid), Tween 80 (nonionic surfactant), and Transcutol P (cosurfactant) were selected for the preparation of SLNs. Initial fractional factorial design suggests that the sonication time and amount of lipid significantly influence the SLN formulation. Further, 3<sup>2</sup> full factorial design data also confirms that both the factors significantly affect the particle size, drug entrapment efficiency, and drug loading. The drug content and entrapment efficiency of SLNs were enhanced by increasing the concentration of lipid since higher hydrophobicity of the longer chain of stearic acid resulted in a high-loaded clarithromycin. Ex vivo permeation and in vivo pharmacokinetics data signify greater efficacy by the optimized clarithromycin-loaded SLN (CL10). Indeed, the clarithromycin observed in the aqueous humor was significantly higher than the minimum effective concentration of clarithromycin in bacterial endophthalmitis. Further, the topical ocular therapy of clarithromycin could be more advantageous than its oral counterpart because topical administration could minimize the side effects as well as diminish the possibility of producing resistant strains of bacteria. Being a noninvasive approach, topical ocular therapy is more preferred and possesses higher patient compliance in the treatment of various diseases in the anterior segment. Thus, the developed SLN of clarithromycin-loaded nanoparticles has greater potential and can be a promising alternative to conventional therapy for the effective management of bacterial endophthalmitis. Further studies need to be carried out to understand the interaction of SLNs with the biological environment for successful commercialization and regulatory approval.

**Author Contributions:** Conceptualization, A.B.N., J.S., B.E.A.-D., and S.J.; Data Curation, A.B.N., J.S., S.S.P., M.A.M., S.G., and M.A.; Formal Analysis, A.B.N., J.S., B.E.A.-D., S.J., S.S.P., K.N.V., and M.A.M.; Funding Acquisition, A.B.N., J.S., B.E.A.-D., K.N.V., M.A.M., M.A., and N.S.; Investigation, A.B.N., J.S., B.E.A.-D., S.J., S.S.P., K.N.V., M.A.M., S.G., M.A., N.S., and P.S.; Methodology, A.B.N., J.S., B.E.A.-D., S.J., S.S.P., K.N.V., M.A.M., S.G., M.A., N.S., and P.S.; Writing—Original Draft Preparation, S.S.P., K.N.V., M.A.M., S.G., M.A., N.S., and P.S.; Writing—Review and Editing, A.B.N., J.S., B.E.A.-D., and S.J. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Deanship of Scientific Research, King Faisal University, grant number 1811021, and the APC was funded by the Deanship of Scientific Research, King Faisal University.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Ethics Committee of Nirma University (protocol Number IP/PCEU/FAC/21/029; dated 9 June 2017).

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** The data presented in this study are contained within the article.

**Acknowledgments:** The authors thank the Deanship of Scientific Research at King Faisal University for the financial support of research project number 1811021.

**Conflicts of Interest:** The authors declare no conflict of interest.
